Multiple Sclerosis
Conditions
Brief summary
Primary Objective: To describe efficacy, tolerability and convenience of teriflunomide treatment through the evaluation of Participant Reported Outcomes (PROs). Secondary Objectives: To describe disease progression using PROs. To describe clinical outcomes (ie, treated relapses) in teriflunomide treated participant. To describe the change in cognition in teriflunomide treated participants. To describe safety of teriflunomide in participant treated (based on adverse events reporting). To describe adherence and persistence to teriflunomide treatment. To describe quality of life, activity and leisure over the period of teriflunomide treatment. To compare Participant Determined Disease Steps (PDDS) and Expanded Disability Status Scale (EDSS) in assessing Multiple Sclerosis (MS) disease progression.
Detailed description
The total duration of the study per participant was up to 50 or 54 weeks (if accelerated elimination procedure performed): Screening: up to 2 weeks Teriflunomide treatment: 48 weeks Accelerated elimination procedure: 4 weeks when performed An accelerated elimination procedure at any time after discontinuation of teriflunomide treatment was possible and it was particularly recommended for women of child-bearing potential.
Interventions
DRUGTeriflunomide
Pharmaceutical form: film-coated tablet; Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants with a relapsing form of multiple sclerosis (RMS) having signed written informed consent.
Exclusion criteria
* According to local labelling, * Less than 18 years of age, * Current or history of receiving teriflunomide, * Previous treatment with leflunomide within 6 months prior to baseline, * Participants with preexisting acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) greater than 2 times the upper limit of normal (ULN), * Known history of active tuberculosis (TB) or latent TB infection, either diagnosed by standard medical practice or guidelines (including skin or blood test, chest X-ray, or as appropriate per local practice), * Known history of severe immunodeficiency, acquired immunodeficiency syndrome (AIDS), bone marrow disease, acute or severe active infections, * Women who were pregnant or breast-feeding, * Female participants with a positive pregnancy test at screening or women of child-bearing potential who did not agree to use reliable contraception throughout the course of the study, * Male participants (only when required according to local labeling): unwilling to use reliable contraception during the course of the study, * Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 - Assessment of Global Satisfaction Subscale Score With Teriflunomide Treatment at Week 48 | Week 48 | TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions:12-14). Primary outcome was the global satisfaction score. The score of the corresponding item was added based on the algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Week 4 in TSQM Scores in Naïve Participants to Week 48 | Week 4, Week 48 | TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions: 12-14). For each of the 4 domains the scores of the corresponding items were added based on an algorithm to create a score of 0 to 100. Higher scores indicated greater satisfaction. |
| Change From Baseline in Disease Progression Using Patient Determined Disease Steps (PDDS) Score at Week 48 | Baseline, Week 48 | PDDS scale developed to assess the disability in Multiple Sclerosis (MS) participants and in assessing disease progression that focuses mainly on how participants walk. PDDS scale consists of 0 = normal; 1 = mild disability; 2 = moderate disability; 3 = gait disability; 4 = early cane; 5 = late cane; 6 = bilateral support; 7 = wheelchair/scooter and 8 = bedridden. A higher score represented higher level of disability. |
| Change From Baseline in Multiple Sclerosis Performance Scale (MSPS) Score at Week 24 and Week 48 | Baseline, Week 24, Week 48 | MSPS was a self-reported measure for MS associated disability in which participants were asked to indicate the category that best described their condition during the past month on the following 8 subscales: mobility, hand function, vision, fatigue, cognitive symptoms, bladder/bowel, sensory symptoms and spasticity symptoms. MSPS used a single question to assess each of 8 subscales. All of the subscales ranged from 0= normal to 5= total disability, except mobility subscale which ranged from 0= normal to 6=total disability. Total MSPS score ranged from 0 =normal to 41=greater disability, where higher score reflected greater disability. |
| Annualized Treated Relapse Rate | Baseline up to end of treatment (up to Week 48) | Annualized treated relapse rate was defined as the total number of treated relapses during the study treatment period divided by the total number participants-years of treatment. Only events occurred during the treatment period (first drug administration to last drug administration) were considered for analysis. |
| Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and Week 48 | Baseline up to end of treatment (up to Week 48) | A treated relapse was defined as a relapse treated by a systemic corticosteroid treatment or by another DMT. If a participant had no treated relapse before treatment discontinuation/completion, then the participant was considered as free of treated relapse until the date of treatment discontinuation/completion. Only treated relapse occurred during the treatment period (first drug administration to last drug administration) were considered for analysis. Kaplan-Meier method was used to estimate the probability of treated MS relapse at 4, 24 and 48 weeks. |
| Change From Baseline in Cognition Measured by Symbol Digit Modalities Test (SDMT) Score at Week 48 | Baseline, Week 48 | SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The score is computed as a ratio of number of correct responses divided by the total number of responses. The test score range from 0 (worst outcome) to 1 (best outcome). Higher scores are indicative of better cognition function. |
| Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Baseline, Week 4, Week 48 | TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions: 12-14). For each of the 4 domains the scores of the corresponding items were added based on an algorithm to create a score of 0 to 100. Higher scores indicated greater satisfaction . |
| Percentage of Participants With Treatment Compliance of ≥80% During the Study Treatment Period | Baseline up to end of treatment (up to Week 48) | Percentage of compliance for a participant was defined as the number of days that the participant was compliant (1 tablet/day) divided by the exposure duration in days (from the first dose administration to the last dose administration) times 100. |
| Duration of Teriflunomide Treatment Exposure | Baseline up to end of treatment (up to Week 48) | Duration of exposure was defined as last dose date - first dose date + 1 day, regardless of unplanned intermittent discontinuations and regardless of dosage administered (14 mg or 7 mg). |
| Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQoL) Score at Week 48 | Baseline, Week 48 | The MusiQoL is a quality of life questionnaire that consists of 31 questions, divided into 9 dimensions: activities of daily living, physiological well-being, symptoms, relationship with friends, relationship with family, sentimental and sexual life, coping, rejection and relationship with healthcare system. All the 9 dimension scores and the global scores are linearly transformed and standardized on 0 (worst outcome) -100 (best outcome) scale. Higher scores represents higher quality of life. |
| Change From Baseline in Stern Leisure Activity Scale at Week 48 | Baseline, Week 48 | The Stern Leisure Activity Scale is a self-reported scale that consists of 13 questions assessing the participant's participation in leisure activities during the preceding month. One point is given for participation in each of the 13 activities and an aggregate score (range from 0 to 13) is obtained. ≤ 6 score is considered as low leisure activity and \> 6 score as high leisure activity. |
| Expanded Disability Status Scale (EDSS) Score at Baseline and Week 48 | Baseline, Week 48 | EDSS is a method of quantifying disability in MS participants and monitoring changes in the level of disability over time. EDSS quantifies disability in 8 functional systems: pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other. EDSS scale ranges from 0 to 10 in 0.5 unit increments that represents higher levels of disability. EDSS score 1.0 to 4.5 refers to people with MS who are fully ambulatory; EDSS score 5.0 to 9.5 refers to impairment to ambulation; EDSS score 10 refers to death due to MS. |
| Overview of Adverse Events (AEs) | From first study drug intake up to 112 days after last intake for participant with no AEP or to last AEP follow up visit for participants with AEP | Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during from first study drug intake up to 112 days after last intake for participant with no accelerated elimination procedure (AEP) or to last AEP follow up visit for participants with AEP. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs. |
Countries
Austria, Belgium, Canada, Chile, Finland, France, Germany, Greece, Italy, Norway, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 169 centers in 14 countries. A total of 1102 participants were screened between June 14, 2013 and November 27, 2014 of whom 101 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment details
A total of 1001 participants were included and 1000 participants were treated in the study. Dose of Teriflunomide tablet was given according to local labelling 14 mg or 7 mg (Teriflunomide 14 mg was the recommended dosage worldwide, except in the US \[where both 7 mg and 14 mg were available\]).
Participants by arm
| Arm | Count |
|---|---|
| Teriflunomide Teriflunomide 14 mg or 7 mg according to local labelling QD orally for 48 weeks. | 1,000 |
| Total | 1,000 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 106 |
| Overall Study | Included But Not treated | 1 |
| Overall Study | Lack of Efficacy | 53 |
| Overall Study | Other than Specified Above | 44 |
| Overall Study | Poor Compliance to Protocol | 11 |
Baseline characteristics
| Characteristic | Teriflunomide |
|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 756 Participants |
| Sex: Female, Male Male | 244 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 498 / 1,000 |
| serious Total, serious adverse events | 127 / 1,000 |
Outcome results
Primary
Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 - Assessment of Global Satisfaction Subscale Score With Teriflunomide Treatment at Week 48
TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions:12-14). Primary outcome was the global satisfaction score. The score of the corresponding item was added based on the algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain.
Time frame: Week 48
Population: Efficacy population that included all treated participants. Number of participants analyzed = participants with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 - Assessment of Global Satisfaction Subscale Score With Teriflunomide Treatment at Week 48 | 68.17 units on a scale | Standard Deviation 27.66 |
Secondary
Annualized Treated Relapse Rate
Annualized treated relapse rate was defined as the total number of treated relapses during the study treatment period divided by the total number participants-years of treatment. Only events occurred during the treatment period (first drug administration to last drug administration) were considered for analysis.
Time frame: Baseline up to end of treatment (up to Week 48)
Population: Analysis was performed on Efficacy population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriflunomide | Annualized Treated Relapse Rate | 0.200 relapses per patient-year |
Secondary
Change From Baseline in Cognition Measured by Symbol Digit Modalities Test (SDMT) Score at Week 48
SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The score is computed as a ratio of number of correct responses divided by the total number of responses. The test score range from 0 (worst outcome) to 1 (best outcome). Higher scores are indicative of better cognition function.
Time frame: Baseline, Week 48
Population: Analysis was performed on Efficacy population. Number of participants analyzed=participants with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | Change From Baseline in Cognition Measured by Symbol Digit Modalities Test (SDMT) Score at Week 48 | 0.00 units on a scale | Standard Deviation 0.06 |
Secondary
Change From Baseline in Disease Progression Using Patient Determined Disease Steps (PDDS) Score at Week 48
PDDS scale developed to assess the disability in Multiple Sclerosis (MS) participants and in assessing disease progression that focuses mainly on how participants walk. PDDS scale consists of 0 = normal; 1 = mild disability; 2 = moderate disability; 3 = gait disability; 4 = early cane; 5 = late cane; 6 = bilateral support; 7 = wheelchair/scooter and 8 = bedridden. A higher score represented higher level of disability.
Time frame: Baseline, Week 48
Population: Analysis was performed on Efficacy population. Number of participants analyzed=participants with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | Change From Baseline in Disease Progression Using Patient Determined Disease Steps (PDDS) Score at Week 48 | -0.01 units on a scale | Standard Deviation 1.05 |
Secondary
Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQoL) Score at Week 48
The MusiQoL is a quality of life questionnaire that consists of 31 questions, divided into 9 dimensions: activities of daily living, physiological well-being, symptoms, relationship with friends, relationship with family, sentimental and sexual life, coping, rejection and relationship with healthcare system. All the 9 dimension scores and the global scores are linearly transformed and standardized on 0 (worst outcome) -100 (best outcome) scale. Higher scores represents higher quality of life.
Time frame: Baseline, Week 48
Population: Analysis was performed on Efficacy population. Number of participants analyzed=participants with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQoL) Score at Week 48 | 0.99 units on a scale | Standard Deviation 10.82 |
Secondary
Change From Baseline in Multiple Sclerosis Performance Scale (MSPS) Score at Week 24 and Week 48
MSPS was a self-reported measure for MS associated disability in which participants were asked to indicate the category that best described their condition during the past month on the following 8 subscales: mobility, hand function, vision, fatigue, cognitive symptoms, bladder/bowel, sensory symptoms and spasticity symptoms. MSPS used a single question to assess each of 8 subscales. All of the subscales ranged from 0= normal to 5= total disability, except mobility subscale which ranged from 0= normal to 6=total disability. Total MSPS score ranged from 0 =normal to 41=greater disability, where higher score reflected greater disability.
Time frame: Baseline, Week 24, Week 48
Population: Analysis was performed on Efficacy population. Here, 'n' signifies number of participants with available data at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | Change From Baseline in Multiple Sclerosis Performance Scale (MSPS) Score at Week 24 and Week 48 | Change at Week 24 (n=854) | -0.61 units on a scale | Standard Deviation 3.89 |
| Teriflunomide | Change From Baseline in Multiple Sclerosis Performance Scale (MSPS) Score at Week 24 and Week 48 | Change at Week 48 (n=875) | -0.06 units on a scale | Standard Deviation 4.33 |
Secondary
Change From Baseline in Stern Leisure Activity Scale at Week 48
The Stern Leisure Activity Scale is a self-reported scale that consists of 13 questions assessing the participant's participation in leisure activities during the preceding month. One point is given for participation in each of the 13 activities and an aggregate score (range from 0 to 13) is obtained. ≤ 6 score is considered as low leisure activity and \> 6 score as high leisure activity.
Time frame: Baseline, Week 48
Population: Analysis was performed on Efficacy population. Number of participants analyzed=participants with available data at specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | Change From Baseline in Stern Leisure Activity Scale at Week 48 | 0.07 units on a scale | Standard Deviation 1.93 |
Secondary
Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48
TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions: 12-14). For each of the 4 domains the scores of the corresponding items were added based on an algorithm to create a score of 0 to 100. Higher scores indicated greater satisfaction .
Time frame: Baseline, Week 4, Week 48
Population: Analysis was performed on Efficacy population. Number of participants analyzed=participants with available data at specified time point. Here, 'n' signifies number of participants with available data for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Global Satisfaction Score Change at Week 4 (n=482) | 21.35 units on a scale | Standard Deviation 27.51 |
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Global Satisfaction Score Change at Week 48(n=457) | 16.55 units on a scale | Standard Deviation 34.29 |
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Effectiveness Score Change at Week 48 (n=453) | 10.19 units on a scale | Standard Deviation 28.9 |
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Side effects Score Change at Week 4 (n=479) | 24.31 units on a scale | Standard Deviation 35.47 |
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Side effects Score Change at Week 48 (n=456) | 19.95 units on a scale | Standard Deviation 39 |
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Convenience Score Change at Week 4 (n=487) | 34.64 units on a scale | Standard Deviation 26.37 |
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Convenience Score Change at Week 48 (n=461) | 32.21 units on a scale | Standard Deviation 27.01 |
| Teriflunomide | Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48 | Effectiveness Score Change at Week 4 (n=477) | 12.02 units on a scale | Standard Deviation 25.53 |
Secondary
Change From Week 4 in TSQM Scores in Naïve Participants to Week 48
TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions: 12-14). For each of the 4 domains the scores of the corresponding items were added based on an algorithm to create a score of 0 to 100. Higher scores indicated greater satisfaction.
Time frame: Week 4, Week 48
Population: Analysis was performed on Efficacy population. Number of participants analyzed=participants with available data at specified time point. Here, 'n' signifies number of participants with available data for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | Change From Week 4 in TSQM Scores in Naïve Participants to Week 48 | Change in Global Satisfaction Score (n=234) | -1.34 units on a scale | Standard Deviation 23.59 |
| Teriflunomide | Change From Week 4 in TSQM Scores in Naïve Participants to Week 48 | Change in Effectiveness Score (n=231) | 1.76 units on a scale | Standard Deviation 27.48 |
| Teriflunomide | Change From Week 4 in TSQM Scores in Naïve Participants to Week 48 | Change in Side effects Score (n=234) | -5.44 units on a scale | Standard Deviation 25.11 |
| Teriflunomide | Change From Week 4 in TSQM Scores in Naïve Participants to Week 48 | Change in Convenience Score (n=235) | 0.33 units on a scale | Standard Deviation 12.96 |
Secondary
Duration of Teriflunomide Treatment Exposure
Duration of exposure was defined as last dose date - first dose date + 1 day, regardless of unplanned intermittent discontinuations and regardless of dosage administered (14 mg or 7 mg).
Time frame: Baseline up to end of treatment (up to Week 48)
Population: Analysis was performed on Safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide | Duration of Teriflunomide Treatment Exposure | 301.6 Days | Standard Deviation 89.1 |
Secondary
Expanded Disability Status Scale (EDSS) Score at Baseline and Week 48
EDSS is a method of quantifying disability in MS participants and monitoring changes in the level of disability over time. EDSS quantifies disability in 8 functional systems: pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other. EDSS scale ranges from 0 to 10 in 0.5 unit increments that represents higher levels of disability. EDSS score 1.0 to 4.5 refers to people with MS who are fully ambulatory; EDSS score 5.0 to 9.5 refers to impairment to ambulation; EDSS score 10 refers to death due to MS.
Time frame: Baseline, Week 48
Population: Analysis was performed on Efficacy population. Number of participants analyzed=participants with available data at specified time point. Here, 'n' signifies number of participants with available data for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide | Expanded Disability Status Scale (EDSS) Score at Baseline and Week 48 | Baseline (n=981) | 3.05 units on a scale | Standard Deviation 1.94 |
| Teriflunomide | Expanded Disability Status Scale (EDSS) Score at Baseline and Week 48 | Week 48 (n=886) | 3.05 units on a scale | Standard Deviation 1.98 |
Secondary
Overview of Adverse Events (AEs)
Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during from first study drug intake up to 112 days after last intake for participant with no accelerated elimination procedure (AEP) or to last AEP follow up visit for participants with AEP. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Time frame: From first study drug intake up to 112 days after last intake for participant with no AEP or to last AEP follow up visit for participants with AEP
Population: Safety Population that included all treated participants who received at least 1 dose or part of a dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | Overview of Adverse Events (AEs) | Any TEAE | 82.3 percentage of participants |
| Teriflunomide | Overview of Adverse Events (AEs) | Any treatment emergent SAE | 12.7 percentage of participants |
| Teriflunomide | Overview of Adverse Events (AEs) | Any TEAE leading to death | 0.4 percentage of participants |
| Teriflunomide | Overview of Adverse Events (AEs) | Any TEAE leading to permanent discontinuation | 10.9 percentage of participants |
Secondary
Percentage of Participants With Treatment Compliance of ≥80% During the Study Treatment Period
Percentage of compliance for a participant was defined as the number of days that the participant was compliant (1 tablet/day) divided by the exposure duration in days (from the first dose administration to the last dose administration) times 100.
Time frame: Baseline up to end of treatment (up to Week 48)
Population: Analysis was performed on Safety population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriflunomide | Percentage of Participants With Treatment Compliance of ≥80% During the Study Treatment Period | 98.2 percentage of participants |
Secondary
Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and Week 48
A treated relapse was defined as a relapse treated by a systemic corticosteroid treatment or by another DMT. If a participant had no treated relapse before treatment discontinuation/completion, then the participant was considered as free of treated relapse until the date of treatment discontinuation/completion. Only treated relapse occurred during the treatment period (first drug administration to last drug administration) were considered for analysis. Kaplan-Meier method was used to estimate the probability of treated MS relapse at 4, 24 and 48 weeks.
Time frame: Baseline up to end of treatment (up to Week 48)
Population: Analysis was performed on Efficacy population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide | Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and Week 48 | Percent Probability of Treated Relapse at Week 4 | 1.8 percent probability of treated relapse |
| Teriflunomide | Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and Week 48 | Percent Probability of Treated Relapse at Week 24 | 9.4 percent probability of treated relapse |
| Teriflunomide | Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and Week 48 | Percent Probability of Treated Relapse at Week 48 | 15.5 percent probability of treated relapse |