Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
Multiple Sclerosis, Relapsing-Remitting, Interferon beta 1a, Rebif®
Brief summary
This is an open-label, multi-center, 12-week, randomized, controlled, parallel group, Phase 4 study to assess whether the morning administration of interferon beta 1a (Rebif®) leads to a lower severity of flu-like symptoms (FLS) as compared to the evening administration, in subjects with relapsing multiple sclerosis (RMS).
Interventions
DRUGRebif®
Rebif® will be administered at a dose of 44 microgram (mcg) subcutaneously three times a week in the morning using RebiSmart® self-injector device for 12 weeks.
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Males and females between 18 and 60 years of age * Female subjects must be neither pregnant nor breast-feeding and must lack child-bearing potential. Furthermore, female subjects must not have been pregnant from at least three months prior to enter in the study * Subjects have RMS according to the revised McDonald Criteria (2010) * Subjects with an expanded disability status scale (EDSS) score of less than 6.0 * Subjects naive to treatment and eligible for treatment with Rebif® 44 three times a week, or patients having received glatiramer acetate with a wash-out from at least one month, or patients having received treatment with natalizumab or fingolimod with a wash-out from at least three months * Subjects able to self-inject treatment using RebiSmart® * Subjects willing and able to comply with the protocol for the duration of the study * Subjects have given written informed consent to take part in the study
Exclusion criteria
* Subjects have any disease other than MS that could better explain his/her signs and symptoms * Subjects who have received any immunosuppressive agents within 3 months prior to Baseline * Subjects who have received any corticosteroids within 30 days prior to Baseline * Subjects have a MS relapse within 30 days prior to Baseline * Subjects have inadequate liver function and bone marrow reserve as defined in the protocol * Subjects have moderate to severe renal impairment * Subjects have any visual or physical impairment that precludes the subjects from self-injecting the treatment using RebiSmart® * Subjects have hypersensitivity to natural or recombinant interferon, or to any of its excipients * Subjects have any contra-indications to treatment with interferon (IFN) beta 1a according to Summary of Product Characteristics (SmPC) * Subjects have any contra-indications to treatment with ibuprofen/paracetamol according to SmPC * Obese subjects, defined by body mass index greater than 30 kilogram per square meter (kg/m\^2) * Subjects have participated in any other investigational trial within 30 days from Baseline * Subjects have any other significant disease that in the Investigator's opinion would exclude the subject from the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 12 | Week 12 | The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 12 is presented in statistical analysis section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Week 4, 8 and 12 | MSTCQ was used as a tool to measure treatment satisfaction, focusing on attributes specific to MS medications. Following sub-scales were assessed: Injection site reactions (ISRs), Global side-effects, Benefits, Pain, Visual Analog Scale (VAS), and Rating of Pain. ISR subscale was defined as sum of scores for questions 17 to 20, with a minimum possible total score of 4 and a maximum possible total score of 20. Global side-effects subscale was defined as sum of scores for questions 21 to 23 with minimum possible total score of 3 and a maximum possible total score of 15. Benefits (question 35); description of pain (question 36); VAS (question 37); rating of pain (question 38) subscales ranged from minimum possible score of 1 and a maximum possible total score of 5. For each of the subscales, lower scores indicated better satisfaction. Difference between both the groups at Week 4, 8 and 12 for individual sub-scales is presented in statistical analysis section. |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Baseline, Week 4, 8 and 12 | HADS was used to measure depression and anxiety in subjects. The scale was limited to 14 questions. Seven of the items related to anxiety and 7 related to depression. Each item on the questionnaire was scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression where higher score indicates more anxiety/depression. |
| Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | Baseline, Week 4, 8 and 12 | FSS is a method designed to assess disabling fatigue in all the individuals. The Fatigue Severity Scale is a 9-item questionnaire developed to assess the level of fatigue due to neurological disease, were each item assessed on a 1-7 scale (1= no fatigue and 7= severe fatigue). The total score was calculated as the average of individual 9-items and ranged from 1 to 7 with a higher value indicating greater impairment due to fatigue. |
| Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | Baseline, Week 4, 8 and 12 | PSQI is a self-rated questionnaire which assess sleep quality and disturbances over a 1-month interval using seven clinically derived components of sleep difficulties: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. PSQI is a summary of 7 components. Each component is scored from 0 to 3, therefore PSQI has a range of 0 (better) to 21 (worse). Interpretation of the PSQI is that a score less than 5 is associated with good sleep quality and a score of 5 or greater is associated with poor sleep quality. |
| Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | Baseline, Week 4, 8 and 12 | The MusiQoL is a validated 31-item questionnaire describing 9 dimensions: activities of daily living (8 items); psychological well-being (4 items); symptoms (3 items); relationships with friends (4 items); relationships with family (3 items); relationship with healthcare system (3 items); sentimental and sexual life (2 items); coping (2 items); and rejection (2 items). Each of the questions was answered using a 6-point Likert scale ranging from 1 (never/not at all) to 6 (always/very much). The scores of each dimension were obtained by computing mean of the item scores of dimension with negatively worded item scores reversed so that higher scores indicated higher health-related quality of life (QoL). All 9 dimension scores were linearly transformed to a 0 to 100 scale and the average of the 9 dimensions was used to give a Global Score ranging from 0 to 100, where higher scores indicated higher health-related quality of life (QoL). |
| Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | Week 4, 8 and 12 | Adherence to treatment was calculated as 100 x the number of completed injections the subject administered divided by the expected number of injections. Treatment adherence was divided in two categories: percentage of subjects with less than (\<) 80 percent adherence and percentage of subjects with more than or equal to (\>=) 80 percent adherence. |
| Change From Baseline in Circulating Levels of Cytokines at Week 12 | Baseline and Week 12 | Results are presented for three cytokines: leptin, resistin and adiponectin. |
| Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4 and 8 | Week 4 and 8 | The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 4 and 8 is presented in statistical analysis section. |
| Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Baseline and Week 12 | Correlation was assessed by using Pearson correlation coefficient. MSTCQ, HADS, FSS, PSQI and MusiQOL are described in the above endpoints. Following abbreviations used in the categories: Global side-effects (GLOBSE); description of pain (PAINDESCR). |
| Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12 | Baseline and Week 12 | Results are presented for cytokines: leptin and resistin. |
| Change From Baseline in Cytokine (Adiponectin) Level at Week 12 | Baseline and Week 12 | — |
| Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Baseline and Week 12 | — |
| Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12 | Baseline and Week 12 | Polysomnography (PSG) was performed for subjects who participated in the sub study. PSG is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. Total sleep time is the total of all REM and non-REM sleep in a sleep episode. |
| Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | Baseline and Week 12 | Correlations between change from baseline at Week 12 in TST or REM sleep and the area under the curve (AUC) calculated using the trapezoidal method for cytokine levels (i.e., leptin, resistin, adiponectin, Interleukin (IL)-12, IL 10, and IL 6) were analyzed using Pearson's correlation coefficient. Polysomnography (PSG) was performed for subjects who participated in the sub study. |
| Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Baseline up to Week 12 | An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. |
| Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | Baseline and Week 12 | Correlation was assessed by using Pearson correlation coefficient. The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to MS medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. |
Countries
Germany
Participant flow
Recruitment details
The study was conducted at 29 clinical trial sites in Italy.
Pre-assignment details
A total of 200 subjects were enrolled in the study, of which 104 were randomized to Rebif morning treatment group, and 96 were randomized to Rebif evening treatment group. A subgroup of subjects also took part in a sub study assessing cytokines and other immunological biomarkers.
Participants by arm
| Arm | Count |
|---|---|
| Rebif Morning Administration Subjects self-injected Rebif at a dose of 44 microgram (mcg) subcutaneously three times a week by using RebiSmart autoinjector device in the morning for 12 weeks. | 104 |
| Rebif Evening Administration Subjects self-injected Rebif at a dose of 44 mcg subcutaneously three times a week by using RebiSmart autoinjector device in the evening for 12 weeks. | 96 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Other | 1 | 3 |
| Overall Study | Therapeutic failure | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Rebif Morning Administration | Rebif Evening Administration | Total |
|---|---|---|---|
| Age, Customized <18 years | 0 subjects | 0 subjects | 0 subjects |
| Age, Customized >=18 years to 64 years | 104 subjects | 96 subjects | 200 subjects |
| Age, Customized >64 years | 0 subjects | 0 subjects | 0 subjects |
| Sex: Female, Male Female | 76 Participants | 62 Participants | 138 Participants |
| Sex: Female, Male Male | 28 Participants | 34 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 104 | 70 / 96 |
| serious Total, serious adverse events | 1 / 104 | 2 / 96 |
Outcome results
Primary
Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 12
The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 12 is presented in statistical analysis section.
Time frame: Week 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Missing data on FLS were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 12 | 12.3 units on scale | Standard Deviation 3.87 |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 12 | 11.8 units on scale | Standard Deviation 3.02 |
p-value: 0.27776395% CI: [-0.46, 1.56]Mann-Whitney Non Parametric test
Secondary
Change From Baseline in Circulating Levels of Cytokines at Week 12
Results are presented for three cytokines: leptin, resistin and adiponectin.
Time frame: Baseline and Week 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Circulating Levels of Cytokines at Week 12 | Leptin: Change at Week 12 | -2.6 microgram per liter (mcg/L) | Standard Deviation 3.42 |
| Rebif Morning Administration | Change From Baseline in Circulating Levels of Cytokines at Week 12 | Resistin: Change at Week 12 | -3.1 microgram per liter (mcg/L) | Standard Deviation 3.31 |
| Rebif Morning Administration | Change From Baseline in Circulating Levels of Cytokines at Week 12 | Adiponectin: Change at Week 12 | 2.8 microgram per liter (mcg/L) | Standard Deviation 6.38 |
| Rebif Evening Administration | Change From Baseline in Circulating Levels of Cytokines at Week 12 | Leptin: Change at Week 12 | -2.6 microgram per liter (mcg/L) | Standard Deviation 3.9 |
| Rebif Evening Administration | Change From Baseline in Circulating Levels of Cytokines at Week 12 | Resistin: Change at Week 12 | -3.0 microgram per liter (mcg/L) | Standard Deviation 3.77 |
| Rebif Evening Administration | Change From Baseline in Circulating Levels of Cytokines at Week 12 | Adiponectin: Change at Week 12 | 2.8 microgram per liter (mcg/L) | Standard Deviation 5.51 |
Secondary
Change From Baseline in Cytokine (Adiponectin) Level at Week 12
Time frame: Baseline and Week 12
Population: The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Rebif Morning Administration | Change From Baseline in Cytokine (Adiponectin) Level at Week 12 | 2.7093 microgram per milliliter (mcg/mL) |
| Rebif Evening Administration | Change From Baseline in Cytokine (Adiponectin) Level at Week 12 | 4.3574 microgram per milliliter (mcg/mL) |
Secondary
Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12
Results are presented for cytokines: leptin and resistin.
Time frame: Baseline and Week 12
Population: The Sub study Analysis Set (SSAS) included all subjects in the ITT who were enrolled in the sub study. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12 | Leptin: Change at Week 12 | -2.7826 Nanogram/milliliter (ng/mL) |
| Rebif Morning Administration | Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12 | Resistin: Change at Week 12 | -3.6628 Nanogram/milliliter (ng/mL) |
| Rebif Evening Administration | Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12 | Leptin: Change at Week 12 | -0.7936 Nanogram/milliliter (ng/mL) |
| Rebif Evening Administration | Change From Baseline in Cytokines (Leptin and Resistin) Levels at Week 12 | Resistin: Change at Week 12 | -5.8360 Nanogram/milliliter (ng/mL) |
Secondary
Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12
FSS is a method designed to assess disabling fatigue in all the individuals. The Fatigue Severity Scale is a 9-item questionnaire developed to assess the level of fatigue due to neurological disease, were each item assessed on a 1-7 scale (1= no fatigue and 7= severe fatigue). The total score was calculated as the average of individual 9-items and ranged from 1 to 7 with a higher value indicating greater impairment due to fatigue.
Time frame: Baseline, Week 4, 8 and 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | Change at Week 4 | 0.2089 units on scale |
| Rebif Morning Administration | Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | Change at Week 8 | 0.2062 units on scale |
| Rebif Morning Administration | Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | Change at Week 12 | 0.1464 units on scale |
| Rebif Evening Administration | Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | Change at Week 4 | 0.06901 units on scale |
| Rebif Evening Administration | Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | Change at Week 8 | 0.1366 units on scale |
| Rebif Evening Administration | Change From Baseline in Fatigue Severity Scale (FSS) Score at Week 4, 8 and 12 | Change at Week 12 | 0.1942 units on scale |
Secondary
Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12
Time frame: Baseline and Week 12
Population: The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Interleukin-6: Change at Week 12 | -0.5173 Pico gram/milliliter (pg/mL) |
| Rebif Morning Administration | Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Interleukin-10: Change at Week 12 | -0.05819 Pico gram/milliliter (pg/mL) |
| Rebif Morning Administration | Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Interleukin-12: Change at Week 12 | -0.3490 Pico gram/milliliter (pg/mL) |
| Rebif Evening Administration | Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Interleukin-6: Change at Week 12 | -0.6970 Pico gram/milliliter (pg/mL) |
| Rebif Evening Administration | Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Interleukin-10: Change at Week 12 | -0.6660 Pico gram/milliliter (pg/mL) |
| Rebif Evening Administration | Change From Baseline in Hormone-Like Cytokine (Interleukin-6, 10 and 12) Levels at Week 12 | Interleukin-12: Change at Week 12 | -0.4384 Pico gram/milliliter (pg/mL) |
Secondary
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12
HADS was used to measure depression and anxiety in subjects. The scale was limited to 14 questions. Seven of the items related to anxiety and 7 related to depression. Each item on the questionnaire was scored from 0-3 giving a total score between 0 and 21 for either anxiety or depression where higher score indicates more anxiety/depression.
Time frame: Baseline, Week 4, 8 and 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Anxiety score: Change at Week 8 | -0.7222 units on scale |
| Rebif Morning Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Depression score: Change at Week 12 | 0.1906 units on scale |
| Rebif Morning Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Anxiety score: Change at Week 12 | -0.6435 units on scale |
| Rebif Morning Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Anxiety score: Change at Week 4 | -0.6625 units on scale |
| Rebif Morning Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Depression score: Change at Week 4 | -0.1539 units on scale |
| Rebif Morning Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Depression score: Change at Week 8 | -0.2397 units on scale |
| Rebif Evening Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Depression score: Change at Week 12 | 0.1162 units on scale |
| Rebif Evening Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Depression score: Change at Week 8 | 0.1999 units on scale |
| Rebif Evening Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Anxiety score: Change at Week 4 | -0.4604 units on scale |
| Rebif Evening Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Anxiety score: Change at Week 8 | -0.3763 units on scale |
| Rebif Evening Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Anxiety score: Change at Week 12 | 0.05023 units on scale |
| Rebif Evening Administration | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score at Week 4, 8 and 12 | Depression score: Change at Week 4 | 0.2211 units on scale |
Secondary
Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12
The MusiQoL is a validated 31-item questionnaire describing 9 dimensions: activities of daily living (8 items); psychological well-being (4 items); symptoms (3 items); relationships with friends (4 items); relationships with family (3 items); relationship with healthcare system (3 items); sentimental and sexual life (2 items); coping (2 items); and rejection (2 items). Each of the questions was answered using a 6-point Likert scale ranging from 1 (never/not at all) to 6 (always/very much). The scores of each dimension were obtained by computing mean of the item scores of dimension with negatively worded item scores reversed so that higher scores indicated higher health-related quality of life (QoL). All 9 dimension scores were linearly transformed to a 0 to 100 scale and the average of the 9 dimensions was used to give a Global Score ranging from 0 to 100, where higher scores indicated higher health-related quality of life (QoL).
Time frame: Baseline, Week 4, 8 and 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | Global Score: Change at Week 4 | 1.6283 units on scale |
| Rebif Morning Administration | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | Global Score: Change at Week 8 | 1.1439 units on scale |
| Rebif Morning Administration | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | Global Score: Change at Week 12 | 0.9670 units on scale |
| Rebif Evening Administration | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | Global Score: Change at Week 4 | 0.1174 units on scale |
| Rebif Evening Administration | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | Global Score: Change at Week 8 | -2.2945 units on scale |
| Rebif Evening Administration | Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQOL) Score at Week 4, 8 and 12 | Global Score: Change at Week 12 | -1.3948 units on scale |
Secondary
Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12
PSQI is a self-rated questionnaire which assess sleep quality and disturbances over a 1-month interval using seven clinically derived components of sleep difficulties: sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. PSQI is a summary of 7 components. Each component is scored from 0 to 3, therefore PSQI has a range of 0 (better) to 21 (worse). Interpretation of the PSQI is that a score less than 5 is associated with good sleep quality and a score of 5 or greater is associated with poor sleep quality.
Time frame: Baseline, Week 4, 8 and 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | Change at Week 8 | -0.4513 units on scale |
| Rebif Morning Administration | Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | Change at Week 12 | 0.07841 units on scale |
| Rebif Morning Administration | Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | Change at Week 4 | -0.08889 units on scale |
| Rebif Evening Administration | Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | Change at Week 4 | 0.5747 units on scale |
| Rebif Evening Administration | Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | Change at Week 8 | 0.7092 units on scale |
| Rebif Evening Administration | Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 4, 8 and 12 | Change at Week 12 | 0.4293 units on scale |
Secondary
Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12
Polysomnography (PSG) was performed for subjects who participated in the sub study. PSG is a multi-parametric test used in the study of sleep and as a diagnostic tool in sleep medicine. Total sleep time is the total of all REM and non-REM sleep in a sleep episode.
Time frame: Baseline and Week 12
Population: The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Rebif Morning Administration | Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12 | Total Sleep Time: Change at Week 12 | 10.0 minutes |
| Rebif Morning Administration | Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12 | REM sleep: Change at Week 12 | -3.0 minutes |
| Rebif Evening Administration | Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12 | Total Sleep Time: Change at Week 12 | 33.0 minutes |
| Rebif Evening Administration | Change From Baseline in Total Sleep Time (TST) and Rapid Eye Movement (REM) Sleep Time at Week 12 | REM sleep: Change at Week 12 | 6.0 minutes |
Secondary
Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12
Correlation was assessed by using Pearson correlation coefficient. MSTCQ, HADS, FSS, PSQI and MusiQOL are described in the above endpoints. Following abbreviations used in the categories: Global side-effects (GLOBSE); description of pain (PAINDESCR).
Time frame: Baseline and Week 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and HADS-depression: Week 12 | 0.05226 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-VAS: Week 12 | 0.34840 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-GLOBSE: Week 12 | 0.03121 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-VAS: Week 12 | -0.15231 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-GLOBSE: Week 12 | 0.20285 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-VAS: Week 12 | -0.07840 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MusiQoL-Global: Week 12 | 0.07152 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-pain rating: Week 12 | 0.16675 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-GLOBSE: Week 12 | 0.00169 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-pain rating: Week 12 | -0.23531 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and HADS-anxiety: Week 12 | 0.06295 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-pain rating: Week12 | -0.08060 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-benefits: Week 12 | 0.13023 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and HADS-anxiety: Week 12 | 0.00754 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-ISR: Week 12 | 0.00595 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and HADS-anxiety: Week 12 | 0.02447 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-benefits: Week 12 | -0.13544 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and HADS-depression: Week 12 | 0.03228 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and HADS-depression: Week 12 | 0.01970 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and FSS: Week 12 | 0.04256 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-benefits: Week 12 | 0.10726 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and FSS: Week 12 | -0.23755 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-ISR: Week 12 | -0.22380 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and FSS: Week 12 | -0.00326 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-PAINDESCR: Week 12 | 0.09118 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and PSQI: Week 12 | 0.00873 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MusiQoL-Global: Week 12 | 0.12190 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and PSQI: Week 12 | -0.03765 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-PAINDESCR: Week 12 | -0.13918 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and PSQI: Week 12 | 0.25795 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-ISR: Week 12 | -0.13365 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MusiQoL- Global: Week 12 | -0.25650 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-PAINDESCR: Week12 | 0.07093 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MusiQoL- Global: Week 12 | 0.17917 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and HADS-anxiety: Week 12 | 0.07986 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and HADS-anxiety: Week 12 | 0.08818 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and HADS-depression: Week 12 | -0.14953 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MusiQoL-Global: Week 12 | 0.21936 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MusiQoL-Global: Week 12 | -0.05924 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-ISR: Week 12 | -0.10214 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-ISR: Week 12 | 0.04855 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-ISR: Week 12 | -0.14865 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-GLOBSE: Week 12 | -0.12730 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-GLOBSE: Week 12 | -0.06398 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-benefits: Week 12 | -0.10915 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-benefits: Week 12 | -0.15636 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-benefits: Week 12 | 0.04081 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-PAINDESCR: Week 12 | 0.01165 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-PAINDESCR: Week 12 | 0.04150 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-PAINDESCR: Week12 | 0.01535 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-VAS: Week 12 | -0.01433 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-VAS: Week 12 | 0.16220 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-VAS: Week 12 | 0.02109 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-pain rating: Week 12 | -0.14381 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and MSTCQ-pain rating: Week 12 | 0.12355 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and MSTCQ-pain rating: Week12 | -0.08718 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and HADS-anxiety: Week 12 | -0.06360 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and HADS-depression: Week 12 | -0.04154 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and HADS-depression: Week 12 | 0.19209 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and FSS: Week 12 | 0.14284 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and FSS: Week 12 | -0.10961 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and FSS: Week 12 | 0.03090 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and PSQI: Week 12 | 0.00099 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Resistin and PSQI: Week 12 | 0.12085 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Adiponectin and PSQI: Week 12 | 0.24406 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines and in Other MSTCQ Items, HADS, FSS, PSQI and MusiQOL Scores at Week 12 | Leptin and MSTCQ-GLOBSE: Week 12 | 0.21425 Correlation Coefficient |
Secondary
Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12
Correlation was assessed by using Pearson correlation coefficient. The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to MS medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction.
Time frame: Baseline and Week 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | Resistin and FLS: Change at Week 12 | -0.20200 Correlation coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | Leptin and FLS: Change at Week 12 | 0.08822 Correlation coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | Adiponectin and FLS: Change at Week 12 | 0.04616 Correlation coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | Leptin and FLS: Change at Week 12 | 0.03944 Correlation coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | Resistin and FLS: Change at Week 12 | -0.01069 Correlation coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Circulating Levels of Cytokines (Leptin, Resistin and Adiponectin) and in Flu Like Symptom (FLS) Score at Week 12 | Adiponectin and FLS: Change at Week 12 | -0.13571 Correlation coefficient |
Secondary
Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12
Correlations between change from baseline at Week 12 in TST or REM sleep and the area under the curve (AUC) calculated using the trapezoidal method for cytokine levels (i.e., leptin, resistin, adiponectin, Interleukin (IL)-12, IL 10, and IL 6) were analyzed using Pearson's correlation coefficient. Polysomnography (PSG) was performed for subjects who participated in the sub study.
Time frame: Baseline and Week 12
Population: The SSAS included all subjects in the ITT who were enrolled in the sub study. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-10 and REM: Week 12 | -1.00000 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Leptin and REM: Week 12 | 0.99732 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-6 and REM: Week 12 | 0.06269 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Leptin and TST: Week 12 | 0.10816 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Resistin and TST: Week 12 | -0.56278 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Adiponectin and TST: Week 12 | 0.17402 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-12 and TST: Week 12 | -0.44328 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-10 and TST: Week 12 | 1.00000 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-6 and TST: Week 12 | 0.18626 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Resistin and REM: Week 12 | 0.22684 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Adiponectin and REM: Week 12 | 0.98335 Correlation Coefficient |
| Rebif Morning Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-12 and REM: Week 12 | 1.00000 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-12 and REM: Week 12 | -0.76606 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-10 and TST: Week 12 | NA Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-10 and REM: Week 12 | NA Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Adiponectin and REM: Week 12 | -0.05732 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-6 and REM: Week 12 | -0.34860 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-6 and TST: Week 12 | -0.51662 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Leptin and TST: Week 12 | 0.46984 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Leptin and REM: Week 12 | 0.63155 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Resistin and TST: Week 12 | -0.05056 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Adiponectin and TST: Week 12 | 0.58181 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC Resistin and REM: Week 12 | -0.38234 Correlation Coefficient |
| Rebif Evening Administration | Correlation Between Change From Baseline in Cytokines (Leptin, Resistin and Adiponectin) and Hormone-like Cytokine Levels (Interleukin-6, 10 and 12), and TST and REM Sleep Time at Week 12 | AUC IL-12 and TST: Week 12 | 0.24717 Correlation Coefficient |
Secondary
Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4 and 8
The MSTCQ was used as a tool to measure treatment satisfaction, focusing on the attributes specific to multiple sclerosis (MS) medications. The FLS subscale of MSTCQ was defined as the sum of the scores for questions 13 to 16 with a minimum possible total FLS score = 1 and a maximum possible total FLS score = 20. Lower score indicates lower flu like symptoms and better satisfaction. Difference between Rebif Morning Administration and Rebif Evening Administration groups at Week 4 and 8 is presented in statistical analysis section.
Time frame: Week 4 and 8
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4 and 8 | Week 4 | 12.4368 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4 and 8 | Week 8 | 13.0039 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4 and 8 | Week 4 | 11.0876 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Flu Like Symptom (FLS) Score Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4 and 8 | Week 8 | 11.6672 units on scale |
Comparison: Week 4p-value: 0.008395% CI: [0.3495, 2.3489]linear mixed model for repeated measures
Comparison: Week 8p-value: 0.007995% CI: [0.3534, 2.32]linear mixed model for repeated measures
Secondary
Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12
MSTCQ was used as a tool to measure treatment satisfaction, focusing on attributes specific to MS medications. Following sub-scales were assessed: Injection site reactions (ISRs), Global side-effects, Benefits, Pain, Visual Analog Scale (VAS), and Rating of Pain. ISR subscale was defined as sum of scores for questions 17 to 20, with a minimum possible total score of 4 and a maximum possible total score of 20. Global side-effects subscale was defined as sum of scores for questions 21 to 23 with minimum possible total score of 3 and a maximum possible total score of 15. Benefits (question 35); description of pain (question 36); VAS (question 37); rating of pain (question 38) subscales ranged from minimum possible score of 1 and a maximum possible total score of 5. For each of the subscales, lower scores indicated better satisfaction. Difference between both the groups at Week 4, 8 and 12 for individual sub-scales is presented in statistical analysis section.
Time frame: Week 4, 8 and 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | VAS: Week 12 | 16.1757 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Global side-effect subscale: Week 4 | 10.2144 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Benefits: Week 4 | 3.1325 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Global side-effect subscale: Week 8 | 10.4111 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Global side-effect subscale: Week 12 | 10.5879 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | VAS: Week 8 | 17.2316 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Benefits: Week 8 | 3.5779 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | ISRs subscale Week 4 | 10.8459 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Benefits: Week 12 | 3.6059 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Description of pain: Week 4 | 4.3755 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Description of pain: Week 12 | 5.7853 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Description of pain: Week 8 | 5.3132 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | ISRs subscale Week 8 | 11.5363 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | VAS: Week 4 | 11.8837 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Rating of pain: Week 4 | 1.3073 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Rating of pain: Week 8 | 1.5653 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Rating of pain: Week 12 | 1.4994 units on scale |
| Rebif Morning Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | ISRs subscale Week 12 | 11.6380 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Rating of pain: Week 12 | 1.7218 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Global side-effect subscale: Week 8 | 10.2214 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Benefits: Week 12 | 3.6640 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Description of pain: Week 12 | 5.6431 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | VAS: Week 4 | 11.2293 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | VAS: Week 8 | 19.4610 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | VAS: Week 12 | 21.5953 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Rating of pain: Week 4 | 1.3004 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Rating of pain: Week 8 | 1.6522 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | ISRs subscale Week 4 | 10.4456 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | ISRs subscale Week 12 | 11.9625 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Global side-effect subscale: Week 4 | 10.2852 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Global side-effect subscale: Week 12 | 10.1782 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Benefits: Week 4 | 3.5408 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Benefits: Week 8 | 3.7137 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Description of pain: Week 4 | 3.7846 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | Description of pain: Week 8 | 6.0821 units on scale |
| Rebif Evening Administration | Difference in Multiple Sclerosis Treatment Concern Questionnaire (MSTCQ) Subscale Scores Between Rebif Morning Administration and Rebif Evening Administration Groups at Week 4, 8 and 12 | ISRs subscale Week 8 | 11.4515 units on scale |
Comparison: ISRs subscale Week 4p-value: 0.431195% CI: [-0.5992, 1.3998]linear mixed model for repeated measures
Comparison: ISRs subscale Week 8p-value: 0.863595% CI: [-0.885, 1.0546]linear mixed model for repeated measures
Comparison: ISRs subscale Week 12p-value: 0.509995% CI: [-1.2927, 0.6437]linear mixed model for repeated measures
Comparison: Global side-effect subscale: Week 4p-value: 0.857495% CI: [-0.8452, 0.7036]linear mixed model for repeated measures
Comparison: Global side-effect subscale: Week 8p-value: 0.633895% CI: [-0.5926, 0.972]linear mixed model for repeated measures
Comparison: Global side-effect subscale: Week 12p-value: 0.304295% CI: [-0.3734, 1.1929]linear mixed model for repeated measures
Comparison: Benefits: Week 4p-value: 0.103895% CI: [-0.9008, 0.08419]linear mixed model for repeated measures
Comparison: Benefits: Week 8p-value: 0.59495% CI: [-0.637, 0.3653]linear mixed model for repeated measures
Comparison: Benefits: Week 12p-value: 0.821795% CI: [-0.5651, 0.4489]linear mixed model for repeated measures
Comparison: Description of pain: Week 4p-value: 0.48995% CI: [-1.0873, 2.269]linear mixed model for repeated measures
Comparison: Description of pain: Week 8p-value: 0.371995% CI: [-2.4607, 0.9229]linear mixed model for repeated measures
Comparison: Description of pain: Week 12p-value: 0.86995% CI: [-1.5521, 1.8364]linear mixed model for repeated measures
Comparison: VAS: Week 4p-value: 0.832895% CI: [-5.4393, 6.7482]linear mixed model for repeated measures
Comparison: VAS: Week 8p-value: 0.476495% CI: [-8.38, 3.9212]linear mixed model for repeated measures
Comparison: VAS: Week 12p-value: 0.085295% CI: [-11.5939, 0.7547]linear mixed model for repeated measures
Comparison: Rating of pain: Week 4p-value: 0.963995% CI: [-0.2918, 0.3055]linear mixed model for repeated measures
Comparison: Rating of pain: Week 8p-value: 0.571595% CI: [-0.3886, 0.2148]linear mixed model for repeated measures
Comparison: Rating of pain: Week 12p-value: 0.150295% CI: [-0.5256, 0.0809]linear mixed model for repeated measures
Secondary
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation
An adverse event (AE) was defined as any untoward medical occurrence in a subject which does not necessarily have a causal relationship with the treatment. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug.
Time frame: Baseline up to Week 12
Population: The Safety Analysis Set (SAF) included all subjects in the ITT who received at least 1 dose of the planned study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif Morning Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 82 Subjects |
| Rebif Morning Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 1 Subjects |
| Rebif Morning Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs Leading to Death | 0 Subjects |
| Rebif Morning Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 6 Subjects |
| Rebif Evening Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAE leading to Discontinuation | 3 Subjects |
| Rebif Evening Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs | 77 Subjects |
| Rebif Evening Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | TEAEs Leading to Death | 0 Subjects |
| Rebif Evening Administration | Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Discontinuation | Serious TEAEs | 2 Subjects |
Secondary
Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12
Adherence to treatment was calculated as 100 x the number of completed injections the subject administered divided by the expected number of injections. Treatment adherence was divided in two categories: percentage of subjects with less than (\<) 80 percent adherence and percentage of subjects with more than or equal to (\>=) 80 percent adherence.
Time frame: Week 4, 8 and 12
Population: The ITT included all subjects enrolled into the study and assigned to the RebiSmart device. Here, Number of Subjects Analyzed signifies those subjects who were evaluable for this outcome measure. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif Morning Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | >= 80 percent adherence at Week 8 | 97.1 Percentage of subjects |
| Rebif Morning Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | < 80 percent adherence at Week 8 | 2.9 Percentage of subjects |
| Rebif Morning Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | < 80 percent adherence at Week 12 | 4.8 Percentage of subjects |
| Rebif Morning Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | >= 80 percent adherence at Week 4 | 96.7 Percentage of subjects |
| Rebif Morning Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | >= 80 percent adherence at Week 12 | 95.2 Percentage of subjects |
| Rebif Morning Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | < 80 percent adherence at Week 4 | 3.3 Percentage of subjects |
| Rebif Evening Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | >= 80 percent adherence at Week 12 | 93.7 Percentage of subjects |
| Rebif Evening Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | < 80 percent adherence at Week 8 | 1.5 Percentage of subjects |
| Rebif Evening Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | < 80 percent adherence at Week 4 | 5.9 Percentage of subjects |
| Rebif Evening Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | >= 80 percent adherence at Week 4 | 94.1 Percentage of subjects |
| Rebif Evening Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | >= 80 percent adherence at Week 8 | 98.5 Percentage of subjects |
| Rebif Evening Administration | Percentage of Subjects With Treatment Adherence at Week 4, 8 and 12 | < 80 percent adherence at Week 12 | 6.3 Percentage of subjects |