Multiple Sclerosis
Conditions
Keywords
Quality of Life, Multiple Sclerosis
Brief summary
The primary objective of the study is to assess the effect of long-term treatment with prolonged-release fampridine (BIIB041) 10 mg twice daily on the physical component scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) as reported by treatment responders. The secondary objectives of this study are to compare the change in the PCS of the SF-36 between treatment responders and non-responders, to evaluate change from baseline in additional quality of life measures among treatment responders as well as changes from baseline in treatment responders versus non-responders and to assess the safety and tolerability of prolonged-release fampridine 10 mg twice daily.
Detailed description
This study has 2 components: a 4-week run-in period during which participants are treated with prolonged-release fampridine and undergo subjective and objective assessments of walking ability, the results of which are used to determine who responded to study treatment, and an observational period, during which treatment responders will continue prolonged-release fampridine treatment. The participants who do not meet the criteria to continue study treatment will be offered the opportunity to continue study participation but will not continue prolonged-release fampridine treatment.
Interventions
DRUGFampridine
Supplied as a 10 mg twice daily tablet and taken twice daily. Doses must be spaced at least 12 hours apart.
Sponsors
Biogen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations. * Must have a diagnosis of primary-progressive, secondary-progressive, progressive-remitting, or relapsing-remitting multiple sclerosis (MS) per revised McDonald Committee criteria (\[Polman et al, 2011\]) as defined by Lublin and Reingold \[Lublin and Reingold 1996\] of at least 3 months duration. * Have a walking impairment as determined by the Investigator. * Able to perform the Timed 25-foot Walk Test with or without a walking aid. * Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment. * Able to understand and comply with the requirements of the protocol. Key
Exclusion criteria
* Known allergy to pyridine-containing substances or to any of the inactive ingredients in the prolonged-release fampridine tablet. * Any history of seizure, epilepsy, or other convulsive disorder, with the exception of febrile seizures in childhood. * An estimated creatinine clearance of \<80 mL/minute. * Subject needs to take medicinal products that are inhibitors of organic cation transporter 2 (OCT2 \[e.g., cimetidine\]). * Female subjects who are currently pregnant or who are considering becoming pregnant while participating in the study. * Female subjects who are currently breastfeeding. * Previous exposure to fampridine. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders | Baseline, Months 3, 6, 9, 12 | The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. Within-group least squares means are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Baseline, Months 3, 6, 9, 12 | EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying United Kingdom (UK) weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Baseline, Months 3, 6, 9, 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Baseline, Months 3, 6, 9, 12 | The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). In contrast to the primary endpoint, this analysis was done using data from both responder and non-responder groups; therefore, 'responder group' and 'visit by responder group interaction' were included as fixed effects. |
| Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, 12 | The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, 12 | The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, and 12 | The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Months 3, 6, 9, and 12 | The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, 12 | The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, 12 | EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, 12 | EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Baseline, Months 3, 6, 9, and 12 | WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | From signing of Informed Consent (SAEs) or from first dose of study treatment (AEs) through Week 50 or Early Termination (14 +/- 7 days after last dose) | AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above. |
| Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Baseline, Months 3, 6, 9, and 12 | EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). |
Countries
Australia, Belgium, Denmark, France, Germany, Italy, Netherlands, Portugal, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Responder Participants took 10 mg fampridine twice daily for the first 4 weeks. If deemed a treatment responder, the participant continued 10 mg fampridine twice daily for 44 weeks. | 707 |
| Non-responder Participants took 10 mg fampridine twice daily for the first 4 weeks. Treatment non-responders continued without treatment by completing quality of life questionnaires. | 128 |
| Total | 835 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 39 |
| Overall Study | Death | 2 |
| Overall Study | Disease Progression | 5 |
| Overall Study | Investigator Decision | 13 |
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Non-compliance With Study Protocol | 15 |
| Overall Study | Other | 52 |
| Overall Study | Run-in Failure | 52 |
| Overall Study | Withdrawal by Subject | 105 |
Baseline characteristics
| Characteristic | Responder | Non-responder | Total |
|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 9.7 | 50.5 years STANDARD_DEVIATION 10 | 49.5 years STANDARD_DEVIATION 9.75 |
| Sex: Female, Male Female | 402 Participants | 79 Participants | 481 Participants |
| Sex: Female, Male Male | 305 Participants | 49 Participants | 354 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 314 / 707 | 41 / 128 | 355 / 835 |
| serious Total, serious adverse events | 76 / 707 | 3 / 128 | 79 / 835 |
Outcome results
Primary
Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. Within-group least squares means are presented.
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders | Month 12 | 2.9 units on a scale | Standard Error 0.37 |
| Responder | Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders | Month 3 | 4.2 units on a scale | Standard Error 0.36 |
| Responder | Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders | Month 6 | 3.4 units on a scale | Standard Error 0.38 |
| Responder | Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders | Month 9 | 3.2 units on a scale | Standard Error 0.37 |
Comparison: Month 3: Mixed effect model for repeated measures with visit, baseline PCS score, baseline Expanded Disability Status Scale (EDSS) score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Difference of Month 3 versus Month 6: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0007mixed effect model
Comparison: Month 9: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Difference of Month 6 versus Month 9: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2531mixed effect model
Comparison: Month 12: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Difference of Month 9 versus Month 12: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2299mixed effect model
Secondary
Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders
EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 8.8 units on a scale | Standard Error 1.26 |
| Responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 8.2 units on a scale | Standard Error 1.25 |
| Responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 8.8 units on a scale | Standard Error 1.06 |
| Responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 10.1 units on a scale | Standard Error 1.17 |
| Responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 8.0 units on a scale | Standard Error 1.22 |
| Non-responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 6.1 units on a scale | Standard Error 1.21 |
| Non-responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 6.5 units on a scale | Standard Error 1.04 |
| Non-responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 8.2 units on a scale | Standard Error 1.15 |
| Non-responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 5.6 units on a scale | Standard Error 1.24 |
| Non-responder | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 6.1 units on a scale | Standard Error 1.26 |
| Primary-Progressive MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 7.9 units on a scale | Standard Error 1.66 |
| Primary-Progressive MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 5.5 units on a scale | Standard Error 1.7 |
| Primary-Progressive MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 7.3 units on a scale | Standard Error 1.53 |
| Primary-Progressive MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 6.0 units on a scale | Standard Error 1.63 |
| Primary-Progressive MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 6.7 units on a scale | Standard Error 1.34 |
| Progressive-Relapsing MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 4.5 units on a scale | Standard Error 3.36 |
| Progressive-Relapsing MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 4.7 units on a scale | Standard Error 2.53 |
| Progressive-Relapsing MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 4.1 units on a scale | Standard Error 3.12 |
| Progressive-Relapsing MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 5.5 units on a scale | Standard Error 3.22 |
| Progressive-Relapsing MS | Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 4.6 units on a scale | Standard Error 2.91 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0649mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1138mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0003mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.185mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0887mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0011mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1853mixed effect model
Secondary
Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders
EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 0.05 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 0.07 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 0.04 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 0.04 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 0.05 units on a scale | Standard Error 0.01 |
| Non-responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 0.05 units on a scale | Standard Error 0.01 |
| Non-responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 0.02 units on a scale | Standard Error 0.01 |
| Non-responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 0.03 units on a scale | Standard Error 0.01 |
| Non-responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 0.06 units on a scale | Standard Error 0.01 |
| Non-responder | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 0.04 units on a scale | Standard Error 0.01 |
| Primary-Progressive MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 0.05 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 0.05 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 0.05 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 0.04 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 0.05 units on a scale | Standard Error 0.02 |
| Progressive-Relapsing MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 0.02 units on a scale | Standard Error 0.04 |
| Progressive-Relapsing MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 0.06 units on a scale | Standard Error 0.03 |
| Progressive-Relapsing MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 0.07 units on a scale | Standard Error 0.03 |
| Progressive-Relapsing MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 0.09 units on a scale | Standard Error 0.04 |
| Progressive-Relapsing MS | Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 0.10 units on a scale | Standard Error 0.04 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0005mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0027mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0167mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0024mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0669mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0018mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0004mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.019mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0106mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0009mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1937mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0445mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6475mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0097mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0386mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0219mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0076mixed effect model
Secondary
Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12
The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 3 | -9.6 units on a scale | Standard Error 1.01 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Overall | -7.8 units on a scale | Standard Error 0.97 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 6 | -7.7 units on a scale | Standard Error 1.03 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 9 | -6.8 units on a scale | Standard Error 1.06 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 12 | -7.0 units on a scale | Standard Error 1.06 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 9 | -0.8 units on a scale | Standard Error 2.26 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 3 | -0.2 units on a scale | Standard Error 1.91 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 12 | -0.5 units on a scale | Standard Error 2.34 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Month 6 | -2.6 units on a scale | Standard Error 2.06 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 | Overall | -1.0 units on a scale | Standard Error 1.77 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5577mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9365mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2008mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0102mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7134mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0066mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8202mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0049mixed effect model
Secondary
Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -6.1 units on a scale | Standard Error 1.13 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -9.0 units on a scale | Standard Error 1.07 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -6.2 units on a scale | Standard Error 1.13 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -7.1 units on a scale | Standard Error 1.1 |
| Responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -7.1 units on a scale | Standard Error 1.02 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -2.6 units on a scale | Standard Error 2.37 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -0.2 units on a scale | Standard Error 2.57 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 1.3 units on a scale | Standard Error 2.7 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 0.2 units on a scale | Standard Error 2.17 |
| Non-responder | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -0.3 units on a scale | Standard Error 2 |
| Primary-Progressive MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -9.5 units on a scale | Standard Error 1.56 |
| Primary-Progressive MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -9.7 units on a scale | Standard Error 1.36 |
| Primary-Progressive MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -11.1 units on a scale | Standard Error 1.49 |
| Primary-Progressive MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -8.9 units on a scale | Standard Error 1.64 |
| Primary-Progressive MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -9.1 units on a scale | Standard Error 1.67 |
| Progressive-Relapsing MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -2.4 units on a scale | Standard Error 4.22 |
| Progressive-Relapsing MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -1.0 units on a scale | Standard Error 3.39 |
| Progressive-Relapsing MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -2.8 units on a scale | Standard Error 3.06 |
| Progressive-Relapsing MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -2.6 units on a scale | Standard Error 3.6 |
| Progressive-Relapsing MS | Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -5.1 units on a scale | Standard Error 4.16 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8767mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3673mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0004mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0273mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9091mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7718mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0038mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.272mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4767mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0553mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0632mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9398mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5655mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0204mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1414mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6279mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2239mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0049mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3457mixed effect model
Secondary
Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -6.5 percentage of impairment while working | Standard Error 2.01 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Overall | -4.2 percentage of impairment while working | Standard Error 1.88 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -3.0 percentage of impairment while working | Standard Error 2.18 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -0.3 percentage of impairment while working | Standard Error 2.22 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -6.9 percentage of impairment while working | Standard Error 2.09 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -8.4 percentage of impairment while working | Standard Error 6.8 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Overall | -8.4 percentage of impairment while working | Standard Error 4.56 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -5.6 percentage of impairment while working | Standard Error 5.38 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -17.9 percentage of impairment while working | Standard Error 6.8 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -1.8 percentage of impairment while working | Standard Error 5.53 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0281mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0654mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.34mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0012mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.749mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3592mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0015mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2967mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8735mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1696mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0089mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0297mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8806mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.217mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2392mixed effect model
Secondary
Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -5.0 percentage of impairment while working | Standard Error 2.49 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -8.6 percentage of impairment while working | Standard Error 2.28 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -2.9 percentage of impairment while working | Standard Error 2.56 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -6.7 percentage of impairment while working | Standard Error 2.2 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -5.8 percentage of impairment while working | Standard Error 1.95 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -8.7 percentage of impairment while working | Standard Error 2.79 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -1.8 percentage of impairment while working | Standard Error 3.17 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 1.4 percentage of impairment while working | Standard Error 3.35 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -8.0 percentage of impairment while working | Standard Error 2.88 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -4.2 percentage of impairment while working | Standard Error 2.43 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -2.5 percentage of impairment while working | Standard Error 3.26 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 0.8 percentage of impairment while working | Standard Error 2.78 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -1.7 percentage of impairment while working | Standard Error 3.38 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 0.5 percentage of impairment while working | Standard Error 3.85 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 6.8 percentage of impairment while working | Standard Error 3.95 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -4.9 percentage of impairment while working | Standard Error 8.51 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -2.9 percentage of impairment while working | Standard Error 7.57 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -7.3 percentage of impairment while working | Standard Error 5.95 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -8.3 percentage of impairment while working | Standard Error 6.88 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -13.1 percentage of impairment while working | Standard Error 8.38 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0032mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0828mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.7756mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.22mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0002mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0061mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.6258mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.6987mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0025mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0021mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.4385mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.2275mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0446mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.5757mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.8936mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.5675mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.2539mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.6673mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0849mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.1187mixed effect model
Secondary
Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -1.9 percentage of impairment while working | Standard Error 2.44 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -6.1 percentage of impairment while working | Standard Error 2.35 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 1.1 percentage of impairment while working | Standard Error 2.49 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -5.6 percentage of impairment while working | Standard Error 2.26 |
| Responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -3.1 percentage of impairment while working | Standard Error 2.1 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -3.8 percentage of impairment while working | Standard Error 5.89 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -19.0 percentage of impairment while working | Standard Error 7.31 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -5.5 percentage of impairment while working | Standard Error 7.56 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -1.0 percentage of impairment while working | Standard Error 6.02 |
| Non-responder | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -7.3 percentage of impairment while working | Standard Error 5 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -8.0 percentage of impairment while working | Standard Error 3.06 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -6.4 percentage of impairment while working | Standard Error 2.69 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -8.1 percentage of impairment while working | Standard Error 3.24 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -5.6 percentage of impairment while working | Standard Error 3.55 |
| Primary-Progressive MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -3.8 percentage of impairment while working | Standard Error 3.65 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -6.0 percentage of impairment while working | Standard Error 18.93 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -3.3 percentage of impairment while working | Standard Error 14.07 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -11.5 percentage of impairment while working | Standard Error 10.86 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -15.9 percentage of impairment while working | Standard Error 13.27 |
| Progressive-Relapsing MS | Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -20.7 percentage of impairment while working | Standard Error 15.27 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1392mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1448mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0187mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.292mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3968mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.642mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.01mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8634mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0134mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8147mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4035mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7385mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0139mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5207mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0091mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2312mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7578mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5575mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4486mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0102mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1185mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7523mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0214mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9826mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6627mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4674mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2965mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1778mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3903mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2794mixed effect model
Secondary
Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -7.8 percentage of overall work impairment | Standard Error 2.43 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -7.7 percentage of overall work impairment | Standard Error 2.49 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -2.4 percentage of overall work impairment | Standard Error 2.86 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -2.9 percentage of overall work impairment | Standard Error 2.47 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Overall | -5.2 percentage of overall work impairment | Standard Error 2.24 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -11.7 percentage of overall work impairment | Standard Error 7.06 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Overall | -8.7 percentage of overall work impairment | Standard Error 5.69 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -4.5 percentage of overall work impairment | Standard Error 6.57 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -2.9 percentage of overall work impairment | Standard Error 6.73 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -15.9 percentage of overall work impairment | Standard Error 9.83 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0219mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1259mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5312mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0022mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4968mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6283mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0016mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6631mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.477mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4027mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1077mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1781mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2422mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0994mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2194mixed effect model
Secondary
Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -10.7 percentage of overall work impairment | Standard Error 2.74 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -7.5 percentage of overall work impairment | Standard Error 2.41 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -9.2 percentage of overall work impairment | Standard Error 2.81 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -5.3 percentage of overall work impairment | Standard Error 2.84 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -4.9 percentage of overall work impairment | Standard Error 3.49 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -2.6 percentage of overall work impairment | Standard Error 4.61 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -6.8 percentage of overall work impairment | Standard Error 3.09 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -10.4 percentage of overall work impairment | Standard Error 3.56 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -11.9 percentage of overall work impairment | Standard Error 3.6 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -2.1 percentage of overall work impairment | Standard Error 3.73 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 0.4 percentage of overall work impairment | Standard Error 4.42 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -3.3 percentage of overall work impairment | Standard Error 4.22 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 1.2 percentage of overall work impairment | Standard Error 5.62 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -0.8 percentage of overall work impairment | Standard Error 3.54 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -1.7 percentage of overall work impairment | Standard Error 4.18 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -9.7 percentage of overall work impairment | Standard Error 11.15 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 2.9 percentage of overall work impairment | Standard Error 9.51 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -6.5 percentage of overall work impairment | Standard Error 8.1 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -6.5 percentage of overall work impairment | Standard Error 6.97 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -12.6 percentage of overall work impairment | Standard Error 8.31 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0022mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0299mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.8135mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.3526mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0039mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.6924mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.7639mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0013mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0011mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.434mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.4224mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.1628mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.5666mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.8315mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.3852mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0652mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.5719mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.9237mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.131mixed effect model
Secondary
Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -1.6 percentage of overall work impairment | Standard Error 3.22 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -7.9 percentage of overall work impairment | Standard Error 2.84 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -1.8 percentage of overall work impairment | Standard Error 2.81 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -7.8 percentage of overall work impairment | Standard Error 2.78 |
| Responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -4.8 percentage of overall work impairment | Standard Error 2.55 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -1.8 percentage of overall work impairment | Standard Error 7.48 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -18.5 percentage of overall work impairment | Standard Error 10.69 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -12.6 percentage of overall work impairment | Standard Error 7.95 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -6.6 percentage of overall work impairment | Standard Error 6.99 |
| Non-responder | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -9.9 percentage of overall work impairment | Standard Error 6.26 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -7.7 percentage of overall work impairment | Standard Error 3.85 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -6.7 percentage of overall work impairment | Standard Error 3.32 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -7.1 percentage of overall work impairment | Standard Error 3.85 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -5.5 percentage of overall work impairment | Standard Error 5.15 |
| Primary-Progressive MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -6.5 percentage of overall work impairment | Standard Error 4.02 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 3.7 percentage of overall work impairment | Standard Error 25.71 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 18.0 percentage of overall work impairment | Standard Error 21.17 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 1.2 percentage of overall work impairment | Standard Error 14.53 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -8.2 percentage of overall work impairment | Standard Error 15.87 |
| Progressive-Relapsing MS | Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -8.6 percentage of overall work impairment | Standard Error 15.29 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0628mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1166mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0451mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9327mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4177mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5885mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0059mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3467mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0654mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3965mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8548mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2405mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0056mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8105mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.047mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6067mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4309mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9761mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6261mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.086mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2884mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8854mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1226mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7249mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5129mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1138mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1086mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5746mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1831mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8917mixed effect model
Secondary
Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -3.0 percentage of work time missed | Standard Error 2.15 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -5.3 percentage of work time missed | Standard Error 1.95 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -0.7 percentage of work time missed | Standard Error 2.24 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -1.1 percentage of work time missed | Standard Error 2.31 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Overall | -2.5 percentage of work time missed | Standard Error 1.87 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -12.1 percentage of work time missed | Standard Error 6.54 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -4.0 percentage of work time missed | Standard Error 5.81 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -9.6 percentage of work time missed | Standard Error 7.77 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -7.6 percentage of work time missed | Standard Error 5.07 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 | Overall | -8.3 percentage of work time missed | Standard Error 4.6 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1795mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0715mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2065mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1649mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4894mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8611mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0073mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1343mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6468mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6441mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2176mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2814mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7533mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0653mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0876mixed effect model
Secondary
Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -6.4 percentage of work time missed | Standard Error 2.23 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -1.9 percentage of work time missed | Standard Error 2.86 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -2.9 percentage of work time missed | Standard Error 2.01 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -3.1 percentage of work time missed | Standard Error 2.49 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -0.3 percentage of work time missed | Standard Error 2.67 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -1.5 percentage of work time missed | Standard Error 2.51 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 2.0 percentage of work time missed | Standard Error 3.68 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -0.1 percentage of work time missed | Standard Error 3.44 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -2.6 percentage of work time missed | Standard Error 3.18 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -5.3 percentage of work time missed | Standard Error 2.79 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -2.2 percentage of work time missed | Standard Error 4.12 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -2.5 percentage of work time missed | Standard Error 2.86 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -3.3 percentage of work time missed | Standard Error 3.15 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -3.3 percentage of work time missed | Standard Error 3.81 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -1.1 percentage of work time missed | Standard Error 4.44 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -1.1 percentage of work time missed | Standard Error 8.51 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -2.7 percentage of work time missed | Standard Error 8.24 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -4.0 percentage of work time missed | Standard Error 5.82 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -10.0 percentage of work time missed | Standard Error 8.77 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -2.3 percentage of work time missed | Standard Error 6.29 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.1471mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.5503mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.3854mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.4893mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.2166mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.4149mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.3849mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.898mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0046mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0594mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.2975mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.7155mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.507mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.5848mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.802mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.254mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.9057mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.9679mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.5875mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.744mixed effect model
Secondary
Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -1.2 percentage of work time missed | Standard Error 2.6 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -3.7 percentage of work time missed | Standard Error 2.43 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -1.0 percentage of work time missed | Standard Error 2.53 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -6.0 percentage of work time missed | Standard Error 2.21 |
| Responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -3.0 percentage of work time missed | Standard Error 2.1 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -10.3 percentage of work time missed | Standard Error 5.52 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -12.8 percentage of work time missed | Standard Error 8.32 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -16.2 percentage of work time missed | Standard Error 7.16 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -8.3 percentage of work time missed | Standard Error 6.14 |
| Non-responder | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -11.9 percentage of work time missed | Standard Error 4.93 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -4.3 percentage of work time missed | Standard Error 2.98 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -2.4 percentage of work time missed | Standard Error 2.72 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -2.0 percentage of work time missed | Standard Error 3.43 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -2.1 percentage of work time missed | Standard Error 4.09 |
| Primary-Progressive MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -1.1 percentage of work time missed | Standard Error 3.79 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 13.9 percentage of work time missed | Standard Error 21.98 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 28.6 percentage of work time missed | Standard Error 17.71 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 14.9 percentage of work time missed | Standard Error 12.11 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 6.4 percentage of work time missed | Standard Error 12.11 |
| Progressive-Relapsing MS | Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 10.6 percentage of work time missed | Standard Error 15.59 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1544mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0167mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3868mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2214mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0743mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1601mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1251mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1764mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5528mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.108mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4644mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0887mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0071mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.064mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1552mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5979mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4444mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3863mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6352mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1265mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6161mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.528mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1769mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4743mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6901mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0245mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7707mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4989mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0387mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4635mixed effect model
Secondary
Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Overall | -11.4 percentage of activity impairment | Standard Error 1.31 |
| Responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -10.4 percentage of activity impairment | Standard Error 1.44 |
| Responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -13.5 percentage of activity impairment | Standard Error 1.42 |
| Responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -9.2 percentage of activity impairment | Standard Error 1.45 |
| Responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -12.3 percentage of activity impairment | Standard Error 1.43 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 12 | -4.4 percentage of activity impairment | Standard Error 3.2 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Overall | -4.1 percentage of activity impairment | Standard Error 2.37 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 6 | -4.7 percentage of activity impairment | Standard Error 2.94 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 9 | -4.1 percentage of activity impairment | Standard Error 3.08 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 | Month 3 | -3.1 percentage of activity impairment | Standard Error 2.83 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.086mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.001mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2777mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0002mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1078mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0082mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1838mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0364mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1714mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1259mixed effect model
Secondary
Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -14.9 percentage of activity impairment | Standard Error 1.79 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -14.9 percentage of activity impairment | Standard Error 1.49 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -13.5 percentage of activity impairment | Standard Error 1.79 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -15.1 percentage of activity impairment | Standard Error 1.76 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -16.2 percentage of activity impairment | Standard Error 1.74 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -11.1 percentage of activity impairment | Standard Error 1.76 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -7.5 percentage of activity impairment | Standard Error 1.78 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -7.1 percentage of activity impairment | Standard Error 1.79 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -13.4 percentage of activity impairment | Standard Error 1.72 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -9.8 percentage of activity impairment | Standard Error 1.47 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -9.0 percentage of activity impairment | Standard Error 2.35 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -7.1 percentage of activity impairment | Standard Error 1.86 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -8.7 percentage of activity impairment | Standard Error 2.29 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -7.1 percentage of activity impairment | Standard Error 2.35 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -3.7 percentage of activity impairment | Standard Error 2.37 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -10.8 percentage of activity impairment | Standard Error 4.46 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -11.0 percentage of activity impairment | Standard Error 4.28 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -12.2 percentage of activity impairment | Standard Error 3.39 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -14.2 percentage of activity impairment | Standard Error 4.35 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -13.0 percentage of activity impairment | Standard Error 4.51 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0001mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0003mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0002mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0102mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0001mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0012mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0026mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0161mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.1151mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.004mixed effect model
Secondary
Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -9.8 percentage of activity impairment | Standard Error 1.55 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -12.7 percentage of activity impairment | Standard Error 1.53 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -8.5 percentage of activity impairment | Standard Error 1.56 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -11.5 percentage of activity impairment | Standard Error 1.54 |
| Responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -10.6 percentage of activity impairment | Standard Error 1.39 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -6.3 percentage of activity impairment | Standard Error 3.4 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -5.9 percentage of activity impairment | Standard Error 3.5 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -1.3 percentage of activity impairment | Standard Error 3.7 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -3.4 percentage of activity impairment | Standard Error 3.24 |
| Non-responder | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -4.2 percentage of activity impairment | Standard Error 2.69 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -14.6 percentage of activity impairment | Standard Error 2.23 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -13.3 percentage of activity impairment | Standard Error 1.83 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -15.7 percentage of activity impairment | Standard Error 2.2 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -12.0 percentage of activity impairment | Standard Error 2.28 |
| Primary-Progressive MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -10.9 percentage of activity impairment | Standard Error 2.31 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 1.6 percentage of activity impairment | Standard Error 5.86 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -1.8 percentage of activity impairment | Standard Error 5.15 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -3.1 percentage of activity impairment | Standard Error 4.15 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -0.5 percentage of activity impairment | Standard Error 5.2 |
| Progressive-Relapsing MS | Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -11.6 percentage of activity impairment | Standard Error 5.72 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1152mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4578mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0125mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0158mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2894mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.723mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0038mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0097mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0628mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9232mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1249mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0093mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0937mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7814mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2561mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0255mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7241mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0427mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0498mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9078mixed effect model
Secondary
Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12
The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 12 | -0.8 units on a scale | Standard Error 0.26 |
| Responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 3 | -2.3 units on a scale | Standard Error 0.23 |
| Responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 6 | -1.4 units on a scale | Standard Error 0.25 |
| Responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 9 | -1.2 units on a scale | Standard Error 0.25 |
| Responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Overall | -1.4 units on a scale | Standard Error 0.22 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 9 | 1.8 units on a scale | Standard Error 0.73 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Overall | 0.8 units on a scale | Standard Error 0.56 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 6 | 0.8 units on a scale | Standard Error 0.7 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 12 | 1.1 units on a scale | Standard Error 0.83 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 | Month 3 | -0.4 units on a scale | Standard Error 0.58 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1324mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4759mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0016mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient errorp-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2489mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0017mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0126mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0033mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1758mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0246mixed effect model
Secondary
Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -2.1 units on a scale | Standard Error 0.25 |
| Responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -1.3 units on a scale | Standard Error 0.24 |
| Responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -0.7 units on a scale | Standard Error 0.29 |
| Responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -1.2 units on a scale | Standard Error 0.27 |
| Responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -1.1 units on a scale | Standard Error 0.27 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 0.6 units on a scale | Standard Error 0.81 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 2.0 units on a scale | Standard Error 0.82 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 1.1 units on a scale | Standard Error 0.93 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 0.8 units on a scale | Standard Error 0.63 |
| Non-responder | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -0.5 units on a scale | Standard Error 0.67 |
| Primary-Progressive MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -2.1 units on a scale | Standard Error 0.46 |
| Primary-Progressive MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -1.9 units on a scale | Standard Error 0.37 |
| Primary-Progressive MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -2.9 units on a scale | Standard Error 0.4 |
| Primary-Progressive MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -1.6 units on a scale | Standard Error 0.46 |
| Primary-Progressive MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -1.0 units on a scale | Standard Error 0.5 |
| Progressive-Relapsing MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 1.1 units on a scale | Standard Error 1.67 |
| Progressive-Relapsing MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -0.0 units on a scale | Standard Error 1.14 |
| Progressive-Relapsing MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 0.8 units on a scale | Standard Error 1.11 |
| Progressive-Relapsing MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 1.3 units on a scale | Standard Error 1.33 |
| Progressive-Relapsing MS | Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 1.0 units on a scale | Standard Error 1.81 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2087mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4487mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0013mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0188mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4243mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9989mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0207mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0161mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4256mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3313mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0238mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.015mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0171mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0007mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5146mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0003mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1224mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0168mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2272mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.057mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5832mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0561mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2971mixed effect model
Secondary
Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -3.2 units on a scale | Standard Error 0.31 |
| Responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -2.3 units on a scale | Standard Error 0.35 |
| Responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -2.0 units on a scale | Standard Error 0.37 |
| Responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -2.4 units on a scale | Standard Error 0.35 |
| Responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -2.5 units on a scale | Standard Error 0.29 |
| Non-responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -1.1 units on a scale | Standard Error 0.27 |
| Non-responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -0.5 units on a scale | Standard Error 0.36 |
| Non-responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -2.1 units on a scale | Standard Error 0.29 |
| Non-responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -1.3 units on a scale | Standard Error 0.34 |
| Non-responder | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -0.7 units on a scale | Standard Error 0.33 |
| Primary-Progressive MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -0.8 units on a scale | Standard Error 0.48 |
| Primary-Progressive MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -0.5 units on a scale | Standard Error 0.39 |
| Primary-Progressive MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 0.7 units on a scale | Standard Error 0.52 |
| Primary-Progressive MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -1.6 units on a scale | Standard Error 0.42 |
| Primary-Progressive MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -0.3 units on a scale | Standard Error 0.48 |
| Progressive-Relapsing MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -1.2 units on a scale | Standard Error 0.97 |
| Progressive-Relapsing MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -1.9 units on a scale | Standard Error 0.77 |
| Progressive-Relapsing MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -1.6 units on a scale | Standard Error 0.88 |
| Progressive-Relapsing MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -2.0 units on a scale | Standard Error 0.88 |
| Progressive-Relapsing MS | Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -1.7 units on a scale | Standard Error 0.7 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1754mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0192mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0001mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0157mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0002mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1012mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0749mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0455mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4699mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0235mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1978mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1977mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.225mixed effect model
Secondary
Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 5.5 units on a scale | Standard Error 1.11 |
| Responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 7.6 units on a scale | Standard Error 1.06 |
| Responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 5.5 units on a scale | Standard Error 1.12 |
| Responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 5.2 units on a scale | Standard Error 1.09 |
| Responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 6.0 units on a scale | Standard Error 1 |
| Non-responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -5.6 units on a scale | Standard Error 2.35 |
| Non-responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -6.1 units on a scale | Standard Error 2.51 |
| Non-responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -7.7 units on a scale | Standard Error 2.67 |
| Non-responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -3.9 units on a scale | Standard Error 2.16 |
| Non-responder | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -5.8 units on a scale | Standard Error 1.95 |
| Primary-Progressive MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 8.6 units on a scale | Standard Error 1.56 |
| Primary-Progressive MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 8.6 units on a scale | Standard Error 1.33 |
| Primary-Progressive MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 8.6 units on a scale | Standard Error 1.49 |
| Primary-Progressive MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 8.7 units on a scale | Standard Error 1.62 |
| Primary-Progressive MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 8.7 units on a scale | Standard Error 1.67 |
| Progressive-Relapsing MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -1.8 units on a scale | Standard Error 4.13 |
| Progressive-Relapsing MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -1.2 units on a scale | Standard Error 3.46 |
| Progressive-Relapsing MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -0.8 units on a scale | Standard Error 3.04 |
| Progressive-Relapsing MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 1.5 units on a scale | Standard Error 3.72 |
| Progressive-Relapsing MS | Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -1.5 units on a scale | Standard Error 4.33 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0029mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8041mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0026mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0689mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7182mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0061mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0179mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6911mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0666mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0158mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6684mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0141mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0042mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7329mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0242mixed effect model
Secondary
Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12
EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 3 | 8.0 units on a scale | Standard Error 1 |
| Responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 9 | 6.3 units on a scale | Standard Error 1.04 |
| Responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 6 | 6.1 units on a scale | Standard Error 1.02 |
| Responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 12 | 6.3 units on a scale | Standard Error 1.05 |
| Responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Overall | 6.7 units on a scale | Standard Error 0.95 |
| Non-responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 12 | -6.0 units on a scale | Standard Error 2.34 |
| Non-responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Overall | -4.4 units on a scale | Standard Error 1.73 |
| Non-responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 3 | -3.2 units on a scale | Standard Error 1.91 |
| Non-responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 6 | -3.6 units on a scale | Standard Error 2.06 |
| Non-responder | Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 | Month 9 | -4.9 units on a scale | Standard Error 2.21 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0111mixed effect model
Comparison: Overall, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.097mixed effect model
Comparison: Month 3, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0789mixed effect model
Comparison: Month 6, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0284mixed effect model
Comparison: Month 9, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0108mixed effect model
Comparison: Month 12, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Secondary
Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12
EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying United Kingdom (UK) weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 12 | 0.04 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Overall | 0.05 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 3 | 0.07 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 6 | 0.05 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 9 | 0.04 units on a scale | Standard Error 0.01 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 9 | 0.01 units on a scale | Standard Error 0.03 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 6 | 0.01 units on a scale | Standard Error 0.02 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Overall | 0.00 units on a scale | Standard Error 0.02 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 12 | -0.01 units on a scale | Standard Error 0.03 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 | Month 3 | 0.01 units on a scale | Standard Error 0.02 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8392mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0162mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6956mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0042mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7949mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0679mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0027mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8053mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2638mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0007mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8502mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0917mixed effect model
Secondary
Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 0.05 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 0.04 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 0.03 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 0.07 units on a scale | Standard Error 0.01 |
| Responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 0.03 units on a scale | Standard Error 0.01 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -0.00 units on a scale | Standard Error 0.03 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 0.02 units on a scale | Standard Error 0.02 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -0.00 units on a scale | Standard Error 0.03 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -0.00 units on a scale | Standard Error 0.02 |
| Non-responder | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -0.03 units on a scale | Standard Error 0.03 |
| Primary-Progressive MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 0.07 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 0.06 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 0.07 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 0.05 units on a scale | Standard Error 0.02 |
| Primary-Progressive MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 0.06 units on a scale | Standard Error 0.02 |
| Progressive-Relapsing MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 0.04 units on a scale | Standard Error 0.05 |
| Progressive-Relapsing MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 0.02 units on a scale | Standard Error 0.05 |
| Progressive-Relapsing MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -0.02 units on a scale | Standard Error 0.04 |
| Progressive-Relapsing MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 0.02 units on a scale | Standard Error 0.03 |
| Progressive-Relapsing MS | Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 0.03 units on a scale | Standard Error 0.04 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9151mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6128mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0331mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1919mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4481mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5454mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0516mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0175mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9371mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0056mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5475mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0699mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.587mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0245mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9926mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0027mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6368mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3358mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5089mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0141mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.428mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0002mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3827mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0748mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5663mixed effect model
Secondary
Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 3 | 4.2 units on a scale | Standard Error 0.55 |
| Responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 9 | 2.3 units on a scale | Standard Error 0.58 |
| Responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 6 | 3.3 units on a scale | Standard Error 0.56 |
| Responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 12 | 2.5 units on a scale | Standard Error 0.57 |
| Responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Overall | 3.1 units on a scale | Standard Error 0.53 |
| Non-responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 12 | -0.6 units on a scale | Standard Error 1.21 |
| Non-responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Overall | 0.1 units on a scale | Standard Error 0.95 |
| Non-responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 3 | -0.6 units on a scale | Standard Error 1.03 |
| Non-responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 6 | 0.6 units on a scale | Standard Error 1.12 |
| Non-responder | Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 | Month 9 | 1.0 units on a scale | Standard Error 1.22 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9073mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0009mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5542mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.581mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.014mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4138mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.274mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6453mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.009mixed effect model
Secondary
Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 3.1 units on a scale | Standard Error 0.7 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 3.5 units on a scale | Standard Error 0.68 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 4.0 units on a scale | Standard Error 0.59 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 4.3 units on a scale | Standard Error 0.67 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 4.9 units on a scale | Standard Error 0.64 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 2.1 units on a scale | Standard Error 0.69 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 2.9 units on a scale | Standard Error 0.66 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 2.6 units on a scale | Standard Error 0.67 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 4.5 units on a scale | Standard Error 0.63 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 3.0 units on a scale | Standard Error 0.58 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 3.2 units on a scale | Standard Error 0.74 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 3.9 units on a scale | Standard Error 0.83 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 3.5 units on a scale | Standard Error 0.89 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 2.7 units on a scale | Standard Error 0.93 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 2.5 units on a scale | Standard Error 0.89 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 2.6 units on a scale | Standard Error 1.54 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 2.0 units on a scale | Standard Error 1.74 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 2.0 units on a scale | Standard Error 1.36 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 0.5 units on a scale | Standard Error 1.68 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 2.9 units on a scale | Standard Error 1.65 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.1398mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0935mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.076mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0019mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0037mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.2489mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0001mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0052mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.7714mixed effect model
Secondary
Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 2.1 units on a scale | Standard Error 0.62 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 4.0 units on a scale | Standard Error 0.59 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 2.1 units on a scale | Standard Error 0.61 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 3.0 units on a scale | Standard Error 0.6 |
| Responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 2.8 units on a scale | Standard Error 0.56 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 0.2 units on a scale | Standard Error 1.29 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 1.3 units on a scale | Standard Error 1.4 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -0.7 units on a scale | Standard Error 1.4 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -1.3 units on a scale | Standard Error 1.18 |
| Non-responder | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -0.1 units on a scale | Standard Error 1.09 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 4.1 units on a scale | Standard Error 0.85 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 3.9 units on a scale | Standard Error 0.74 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 4.8 units on a scale | Standard Error 0.81 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 2.8 units on a scale | Standard Error 0.89 |
| Primary-Progressive MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 3.9 units on a scale | Standard Error 0.87 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 0.0 units on a scale | Standard Error 2.24 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 1.1 units on a scale | Standard Error 1.82 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 0.6 units on a scale | Standard Error 1.64 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 1.5 units on a scale | Standard Error 1.96 |
| Progressive-Relapsing MS | Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -0.3 units on a scale | Standard Error 2.15 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8999mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7156mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.005mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.049mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.274mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5556mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0476mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8627mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4312mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0305mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2059mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0008mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3685mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0016mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9862mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5561mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2281mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0006mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6004mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.904mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0401mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0651mixed effect model
Secondary
Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -15.0 units on a scale | Standard Error 1.16 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -10.5 units on a scale | Standard Error 1.27 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -10.9 units on a scale | Standard Error 1.27 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -12.1 units on a scale | Standard Error 1.12 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -12.0 units on a scale | Standard Error 1.22 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -10.3 units on a scale | Standard Error 1.09 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -13.3 units on a scale | Standard Error 1.13 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -10.9 units on a scale | Standard Error 1.19 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -8.9 units on a scale | Standard Error 1.25 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -8.2 units on a scale | Standard Error 1.25 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -8.3 units on a scale | Standard Error 1.4 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -8.4 units on a scale | Standard Error 1.58 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -6.2 units on a scale | Standard Error 1.66 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -7.9 units on a scale | Standard Error 1.67 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -10.6 units on a scale | Standard Error 1.47 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -12.6 units on a scale | Standard Error 2.72 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -11.9 units on a scale | Standard Error 3.15 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -12.5 units on a scale | Standard Error 2.58 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -14.9 units on a scale | Standard Error 2.94 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -10.4 units on a scale | Standard Error 3.13 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0009mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0002mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0002mixed effect model
Secondary
Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -8.0 units on a scale | Standard Error 1.13 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -12.6 units on a scale | Standard Error 1.07 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -7.8 units on a scale | Standard Error 1.13 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -10.0 units on a scale | Standard Error 1.1 |
| Responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -9.6 units on a scale | Standard Error 1.05 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -2.2 units on a scale | Standard Error 2.28 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -0.4 units on a scale | Standard Error 2.48 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -2.1 units on a scale | Standard Error 2.57 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -1.4 units on a scale | Standard Error 2.08 |
| Non-responder | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -1.5 units on a scale | Standard Error 2.03 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -12.2 units on a scale | Standard Error 1.52 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -12.2 units on a scale | Standard Error 1.38 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -14.0 units on a scale | Standard Error 1.43 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -11.8 units on a scale | Standard Error 1.61 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -11.1 units on a scale | Standard Error 1.61 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 0.5 units on a scale | Standard Error 4.02 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -4.0 units on a scale | Standard Error 3.22 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -3.2 units on a scale | Standard Error 3.1 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -5.2 units on a scale | Standard Error 3.47 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -4.3 units on a scale | Standard Error 3.95 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.454mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2949mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0046mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.502mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2157mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0026mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3435mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1357mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0004mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0511mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8703mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.9049mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0019mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0033mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4087mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2755mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0251mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0989mixed effect model
Secondary
Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -8.3 units on a scale | Standard Error 1.29 |
| Responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -9.4 units on a scale | Standard Error 1.09 |
| Responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -8.8 units on a scale | Standard Error 1.23 |
| Responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -9.3 units on a scale | Standard Error 1.29 |
| Responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -11.2 units on a scale | Standard Error 1.17 |
| Non-responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -5.3 units on a scale | Standard Error 1.28 |
| Non-responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -5.1 units on a scale | Standard Error 1.27 |
| Non-responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -6.8 units on a scale | Standard Error 1.22 |
| Non-responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -8.9 units on a scale | Standard Error 1.15 |
| Non-responder | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -6.5 units on a scale | Standard Error 1.07 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -8.3 units on a scale | Standard Error 1.37 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -8.7 units on a scale | Standard Error 1.62 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -8.2 units on a scale | Standard Error 1.7 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -9.1 units on a scale | Standard Error 1.51 |
| Primary-Progressive MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -7.4 units on a scale | Standard Error 1.71 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | -8.6 units on a scale | Standard Error 2.8 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | -8.3 units on a scale | Standard Error 3.21 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | -7.5 units on a scale | Standard Error 2.53 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | -5.1 units on a scale | Standard Error 3.29 |
| Progressive-Relapsing MS | Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | -7.9 units on a scale | Standard Error 3.06 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0032mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0021mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0097mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0103mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.1227mixed effect model
Secondary
Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12
The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 3 | -13.0 units on a scale | Standard Error 1 |
| Responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 9 | -8.9 units on a scale | Standard Error 1.06 |
| Responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 6 | -10.6 units on a scale | Standard Error 1.03 |
| Responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 12 | -8.6 units on a scale | Standard Error 1.06 |
| Responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Overall | -10.3 units on a scale | Standard Error 0.99 |
| Non-responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 12 | -2.8 units on a scale | Standard Error 2.23 |
| Non-responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Overall | -2.1 units on a scale | Standard Error 1.79 |
| Non-responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 3 | -2.1 units on a scale | Standard Error 1.83 |
| Non-responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 6 | -3.0 units on a scale | Standard Error 1.99 |
| Non-responder | Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 | Month 9 | -0.3 units on a scale | Standard Error 2.19 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2475mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2422mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1262mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8858mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.2111mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0072mixed effect model
Secondary
Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, and 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 4.2 units on a scale | Standard Error 0.45 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 4.0 units on a scale | Standard Error 0.45 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 5.5 units on a scale | Standard Error 0.42 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 4.5 units on a scale | Standard Error 0.39 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 4.4 units on a scale | Standard Error 0.46 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 3.9 units on a scale | Standard Error 0.45 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 3.2 units on a scale | Standard Error 0.45 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 4.5 units on a scale | Standard Error 0.41 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 3.8 units on a scale | Standard Error 0.38 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 3.4 units on a scale | Standard Error 0.45 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 1.7 units on a scale | Standard Error 0.61 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 3.1 units on a scale | Standard Error 0.55 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 2.3 units on a scale | Standard Error 0.61 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 3.0 units on a scale | Standard Error 0.6 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 2.5 units on a scale | Standard Error 0.49 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 3 | 2.7 units on a scale | Standard Error 1.01 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 12 | 2.9 units on a scale | Standard Error 1.14 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Overall | 3.2 units on a scale | Standard Error 0.89 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 9 | 3.2 units on a scale | Standard Error 1.12 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders | Month 6 | 3.9 units on a scale | Standard Error 1.13 |
Comparison: Overall, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Overall, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0004mixed effect model
Comparison: Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0069mixed effect model
Comparison: Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0001mixed effect model
Comparison: Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0006mixed effect model
Comparison: Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.004mixed effect model
Comparison: Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: <0.0001mixed effect model
Comparison: Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0047mixed effect model
Comparison: Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.p-value: 0.0118mixed effect model
Secondary
Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 2.5 units on a scale | Standard Error 0.4 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 2.7 units on a scale | Standard Error 0.4 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 3.1 units on a scale | Standard Error 0.36 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 3.1 units on a scale | Standard Error 0.4 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 4.0 units on a scale | Standard Error 0.38 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 0.1 units on a scale | Standard Error 0.77 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 0.6 units on a scale | Standard Error 0.89 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -1.2 units on a scale | Standard Error 0.91 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | -0.8 units on a scale | Standard Error 0.94 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -0.3 units on a scale | Standard Error 0.71 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 3.6 units on a scale | Standard Error 0.58 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | 4.1 units on a scale | Standard Error 0.53 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | 3.9 units on a scale | Standard Error 0.58 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | 3.9 units on a scale | Standard Error 0.48 |
| Primary-Progressive MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | 4.0 units on a scale | Standard Error 0.58 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 3 | -1.2 units on a scale | Standard Error 1.19 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Overall | -0.6 units on a scale | Standard Error 1.08 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 12 | 0.2 units on a scale | Standard Error 1.44 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 9 | -0.7 units on a scale | Standard Error 1.46 |
| Progressive-Relapsing MS | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy | Month 6 | -0.8 units on a scale | Standard Error 1.35 |
Comparison: Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6769mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.578mixed effect model
Comparison: Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8886mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.3221mixed effect model
Comparison: Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4668mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5695mixed effect model
Comparison: Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0058mixed effect model
Comparison: Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.001mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.204mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.6306mixed effect model
Comparison: Month 9, Responder (Taking Additional MS Therapy) versus Non- responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.002mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.4052mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.8626mixed effect model
Comparison: Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0004mixed effect model
Comparison: Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.0263mixed effect model
Secondary
Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). In contrast to the primary endpoint, this analysis was done using data from both responder and non-responder groups; therefore, 'responder group' and 'visit by responder group interaction' were included as fixed effects.
Time frame: Baseline, Months 3, 6, 9, 12
Population: Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 3 | 4.0 units on a scale | Standard Error 0.36 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 6 | 3.3 units on a scale | Standard Error 0.37 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 9 | 3.0 units on a scale | Standard Error 0.37 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 12 | 2.8 units on a scale | Standard Error 0.37 |
| Responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Overall | 3.3 units on a scale | Standard Error 0.34 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 12 | -0.5 units on a scale | Standard Error 0.81 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Overall | -0.4 units on a scale | Standard Error 0.63 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 3 | -0.2 units on a scale | Standard Error 0.67 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 6 | 0.2 units on a scale | Standard Error 0.77 |
| Non-responder | Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders | Month 9 | -1.1 units on a scale | Standard Error 0.8 |
Comparison: Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.5405mixed effect model
Comparison: Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7272mixed effect model
Comparison: Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.7484mixed effect model
Comparison: Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.1877mixed effect model
Comparison: Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Comparison: Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: 0.546mixed effect model
Comparison: Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.p-value: <0.0001mixed effect model
Secondary
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.
Time frame: From signing of Informed Consent (SAEs) or from first dose of study treatment (AEs) through Week 50 or Early Termination (14 +/- 7 days after last dose)
Population: Intent-to-treat population: all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Severe AE | 48 participants |
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE | 522 participants |
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Study treatment related AE | 248 participants |
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE leading to study discontinuation | 18 participants |
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAE | 76 participants |
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Study treatment related SAE | 7 participants |
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE leading to study drug discontinuation | 32 participants |
| Responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Death | 2 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAE | 3 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Death | 0 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE | 64 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE leading to study drug discontinuation | 8 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE leading to study discontinuation | 1 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Severe AE | 2 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Study treatment related AE | 37 participants |
| Non-responder | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Study treatment related SAE | 0 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE leading to study discontinuation | 19 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE | 586 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAE | 79 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Severe AE | 50 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Study treatment related AE | 285 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Study treatment related SAE | 7 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | Death | 2 participants |
| Primary-Progressive MS | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AE leading to study drug discontinuation | 40 participants |