Multiple Sclerosis
Conditions
Keywords
Relapsing-remitting multiple sclerosis
Brief summary
Primary objective was to assess the effectiveness evaluated by the time to failure of two doses of teriflunomide in comparison to interferon beta-1a in participants with relapsing Multiple Sclerosis \[MS\]. Secondary objectives were: * To assess the effect of the two doses in comparison to interferon beta-1a on: * Frequency of relapses, * Fatigue, * Participant's satisfaction with treatment. * To evaluate the safety and tolerability of the two doses in comparison to interferon beta-1a. The study consisted of a core treatment period with a common end date defined as 48 weeks after randomization of the last participant, followed by an optional long-term extension treatment period until teriflunomide is commercially available in accordance with local regulations.
Detailed description
The core treatment period per participant was variable depending on the enrollment in the study (maximum of approximatively 118 weeks). The two doses of teriflunomide were administered in double-blind fashion, whereas interferon beta-1a (Rebif®) was open-label. The opportunity to continue with the highest dose of teriflunomide in open-label fashion was offered to the participants who successfully completed treatment in the core study. The overall treatment period was followed by a 4-week elimination follow-up period.
Interventions
DRUGInterferon β-1a
Sterile preservative-free solution packaged in graduated pre-filled syringes Subcutaneous injection Ascending doses from 8.8 to 44 mcg according to local standard for Rebif®
DRUGTeriflunomide
Film-coated tablet Oral administration
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsing form of MS meeting McDonald's criteria for MS diagnosis and Expanded Disability Status Scale \[EDSS\] score ≤5.5 at screening visit.
Exclusion criteria
* Significantly impaired bone marrow function or, significant anemia, leukopenia or thrombocytopenia; * Persistent significant or severe infection. * Liver function impairment or known history of hepatitis. * Use of adrenocorticotrophic hormone \[ACTH\] or systemic corticosteroids for 2 weeks prior to randomization. * Human immunodeficiency virus \[HIV\] positive. * Prior use of Rebif®, or prior or concomitant use of other interferons in the 3 months prior to randomization. * Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate, mycophenolate, or natalizumab. * Pregnant or breast-feeding woman. Extension criteria: The participants who met all the following criteria at the end of the core study period were eligible for enrolment into the open-label extension phase: * Participants who had not discontinued treatment in the core period and who had a minimum treatment of 48 weeks and completed the EOT visit (Visit 18). * Participants who had not met criteria for treatment withdrawal. * An informed consent must be obtained in writing from the participant for this open-label extension phase prior to entering and prior to completion of any extension phase procedure. * Participants who demonstrated a willingness and ability to roll over to the extension phase with the opportunity to continue treatment on 14 mg/day of teriflunomide under open-label. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Treatment Period: Overview of Failures | Core treatment period between 48 and 118 weeks depending on when the participant was enrolled | Failure was defined as the first occurence of confirmed relapse or permanent treatment discontinuation (for any cause) which ever came first. If no events occurred, the participant was considered free of failure. Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale \[EDSS\] score or Functional System scores. |
| Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Core treatment period between 48 and 118 weeks depending on when the participant was enrolled | Probability of disability progression at 24, 48 and 96 weeks was estimated using Kaplan-Meier method on the time to failure defined as the time from randomization to failure. Participants free of failure were censored at the date of last treatment. Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | 48 weeks | TSQM version 1.4 is an instrument to assess patients' satisfaction with medication. It consists of 13 questions that cover three dimensions (effectiveness, side effects and convenience) plus a global satisfaction question. Four scores ranging from 0 to 100 (extremely satisfied) are obtained. Least-square means were estimated using a Mixed-effect model with repeated measures \[MMRM\] on TSQM score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction as factors). |
| Core Treatment Period: Overview of Adverse Events [AE] | from first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first | AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. |
| Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates | Core treatment period between 48 and 118 weeks depending on when the participant was enrolled | ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrollment and baseline EDSS stratum as covariates). |
| Extension Treatment Period: ARR Poisson Regression Estimates | Extension treatment period (Maximum: 197 weeks) | ARR was obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of the standardized treatment durations.To account for the different treatment durations among participants, a Poisson Regression Model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrolment and baseline EDSS stratum as covariates). |
| Extension Treatment Period: Overview of AEs | From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period | AEs were any unfavourable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. |
| Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score | Baseline (before randomization) and 48 weeks | FIS is a subject-reported scale that qualifies the impact of fatigue on daily life in patients with MS. It consists of 40 statements that measure fatigue in three areas; physical, cognitive, and social. FIS total score ranges from 0 (no problem) to 160 (extreme problem). Least-square means were estimated using a Mixed-effect model with repeated measures \[MMRM\] on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). |
Countries
Belgium, Canada, Czechia, France, Germany, Greece, Hungary, Italy, Poland, Spain, Switzerland, Tunisia, United Kingdom
Participant flow
Recruitment details
The recruitment initiated in April 2009 was completed in July 2010. A total of 369 participants were screened at 54 sites in 13 countries. The common end date of core treatment period was 14 September 2011 (maximum treatment duration of 115 weeks). The end date of extension was 13 May 2015 (maximum treatment duration of 197 weeks)
Pre-assignment details
Randomization was stratified by country and baseline disability (Expanded Disability Status Scale \[EDSS\] score ≤3.5 or \>3.5). Assignment to groups was done centrally using an Interactive Voice Response System (IVRS\] in a 1:1:1 ratio after confirmation of the selection criteria. 324 participants were randomized at 53 sites.
Participants by arm
| Arm | Count |
|---|---|
| Teriflunomide 7 mg / 14 mg Core treatment period: Teriflunomide 7 mg once daily
Extension treatment period: Teriflunomide 14 mg once daily | 109 |
| Teriflunomide 14 mg/14 mg Core treatment period: Teriflunomide 14 mg once daily.
Extension treatment period: Teriflunomide 14 mg once daily. | 111 |
| IFNβ1a / Teriflunomide 14 mg Core treatment period: Interferon β-1a 3 times a week.
Extension treatment period: Teriflunomide 14 mg once daily. | 104 |
| Total | 324 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Core Treatment Period | Adverse Event | 9 | 12 | 22 |
| Core Treatment Period | Lack of Efficacy | 7 | 4 | 2 |
| Core Treatment Period | Lost to Follow-up | 1 | 1 | 0 |
| Core Treatment Period | Other than above | 0 | 1 | 1 |
| Core Treatment Period | Poor compliance to protocol | 0 | 0 | 1 |
| Core Treatment Period | Wish to be pregnant | 1 | 2 | 1 |
| Core Treatment Period | Withdrawal by Subject | 2 | 2 | 6 |
| Extension Treatment Period | Adverse Event | 8 | 5 | 5 |
| Extension Treatment Period | Lack of Efficacy | 8 | 8 | 8 |
| Extension Treatment Period | Lost to Follow-up | 1 | 0 | 0 |
| Extension Treatment Period | Other than above | 10 | 9 | 5 |
| Extension Treatment Period | Poor compliance to protocol | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Teriflunomide 14 mg/14 mg | Total | Teriflunomide 7 mg / 14 mg | IFNβ1a / Teriflunomide 14 mg |
|---|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 10.3 | 36.3 years STANDARD_DEVIATION 10 | 32.5 years STANDARD_DEVIATION 9.2 | 37.0 years STANDARD_DEVIATION 10.6 |
| Baseline EDSS score ≤3.5 | 95 participants | 284 participants | 96 participants | 93 participants |
| Baseline EDSS score >3.5 | 16 participants | 40 participants | 13 participants | 11 participants |
| MS subtype Progressive Relapsing | 2 participants | 2 participants | 0 participants | 0 participants |
| MS subtype Relapsing Remitting | 108 participants | 321 participants | 109 participants | 104 participants |
| MS subtype Secondary Progressive | 1 participants | 1 participants | 0 participants | 0 participants |
| Number of MS relapses Within the past 2 years | 2 relapses | 2 relapses | 2 relapses | 2 relapses |
| Number of MS relapses Within the past year | 1 relapses | 1 relapses | 1 relapses | 1 relapses |
| Region of enrollment Eastern Europe | 41 participants | 115 participants | 39 participants | 35 participants |
| Region of enrollment North America | 6 participants | 21 participants | 8 participants | 7 participants |
| Region of enrollment Western Europe* | 64 participants | 188 participants | 62 participants | 62 participants |
| Sex: Female, Male Female | 78 Participants | 219 Participants | 70 Participants | 71 Participants |
| Sex: Female, Male Male | 33 Participants | 105 Participants | 39 Participants | 33 Participants |
| Time since first diagnosis of Multiple Sclerosis [MS] | 3.68 years STANDARD_DEVIATION 6.24 | 3.74 years STANDARD_DEVIATION 5.71 | 3.72 years STANDARD_DEVIATION 5.19 | 3.82 years STANDARD_DEVIATION 5.69 |
| Time since most recent MS relapse onset | 7.90 months STANDARD_DEVIATION 10.34 | 8.88 months STANDARD_DEVIATION 11.79 | 9.00 months STANDARD_DEVIATION 13.96 | 9.79 months STANDARD_DEVIATION 10.72 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 85 / 110 | 92 / 110 | 92 / 101 | 72 / 90 | 65 / 88 | 48 / 59 |
| serious Total, serious adverse events | 12 / 110 | 6 / 110 | 7 / 101 | 9 / 90 | 13 / 88 | 12 / 59 |
Outcome results
Primary
Core Treatment Period: Overview of Failures
Failure was defined as the first occurence of confirmed relapse or permanent treatment discontinuation (for any cause) which ever came first. If no events occurred, the participant was considered free of failure. Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale \[EDSS\] score or Functional System scores.
Time frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
Population: Intent-to-treat population: all randomized participants. Participants were considered in the treatment group to which they were randomized regardless of the drug they actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide 7 mg | Core Treatment Period: Overview of Failures | Failure | 53 participants |
| Teriflunomide 7 mg | Core Treatment Period: Overview of Failures | Free of failure | 56 participants |
| Teriflunomide 14 mg | Core Treatment Period: Overview of Failures | Failure | 42 participants |
| Teriflunomide 14 mg | Core Treatment Period: Overview of Failures | Free of failure | 69 participants |
| IFN-β-1a | Core Treatment Period: Overview of Failures | Free of failure | 60 participants |
| IFN-β-1a | Core Treatment Period: Overview of Failures | Failure | 44 participants |
Primary
Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints
Probability of disability progression at 24, 48 and 96 weeks was estimated using Kaplan-Meier method on the time to failure defined as the time from randomization to failure. Participants free of failure were censored at the date of last treatment. Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.
Time frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide 7 mg | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 48 weeks | 35.8 percent probability |
| Teriflunomide 7 mg | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 24 weeks | 25.7 percent probability |
| Teriflunomide 7 mg | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 96 weeks | 58.8 percent probability |
| Teriflunomide 14 mg | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 48 weeks | 33.3 percent probability |
| Teriflunomide 14 mg | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 24 weeks | 24.3 percent probability |
| Teriflunomide 14 mg | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 96 weeks | 41.1 percent probability |
| IFN-β-1a | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 24 weeks | 29.8 percent probability |
| IFN-β-1a | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 96 weeks | 44.4 percent probability |
| IFN-β-1a | Core Treatment Period: Time to Failure: Kaplan-Meier Estimates of the Rate of Failure at Timepoints | Probability of failure at 48 weeks | 36.5 percent probability |
Comparison: The study was sized to detect a difference between Teriflunomide and Rebif groups in the time to failure at a significance level of 0.025 with a power of 81%.~Null hypothesis:~* H1: No difference between Teriflunomide 14 mg and Rebif~* H2: No difference between Teriflunomide 7 mg and Rebifp-value: 0.5953Log Rank
Comparison: Null hypothesis:~* H1: No difference between Teriflunomide 14 mg and Rebif~* H2: No difference between Teriflunomide 7 mg and Rebifp-value: 0.519Log Rank
Secondary
Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates
ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrollment and baseline EDSS stratum as covariates).
Time frame: Core treatment period between 48 and 118 weeks depending on when the participant was enrolled
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriflunomide 7 mg | Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates | 0.410 relapses per year |
| Teriflunomide 14 mg | Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates | 0.259 relapses per year |
| IFN-β-1a | Core Treatment Period: Annualized Relapse Rate [ARR] - Poisson Regression Estimates | 0.216 relapses per year |
Secondary
Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score
FIS is a subject-reported scale that qualifies the impact of fatigue on daily life in patients with MS. It consists of 40 statements that measure fatigue in three areas; physical, cognitive, and social. FIS total score ranges from 0 (no problem) to 160 (extreme problem). Least-square means were estimated using a Mixed-effect model with repeated measures \[MMRM\] on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors).
Time frame: Baseline (before randomization) and 48 weeks
Population: ITT population.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Teriflunomide 7 mg | Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score | 0.97 units on a scale | Standard Error 2.96 |
| Teriflunomide 14 mg | Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score | 4.10 units on a scale | Standard Error 3.03 |
| IFN-β-1a | Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score | 9.10 units on a scale | Standard Error 3.21 |
Secondary
Core Treatment Period: Overview of Adverse Events [AE]
AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time frame: from first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first
Population: Safety population: all randomized and treated participants. Participants were considered according to the drug actually received.~The participant randomized to Teriflunomide 14 mg group who received Teriflunomide 7 mg was analyzed in the Teriflunomide 7 mg group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide 7 mg | Core Treatment Period: Overview of Adverse Events [AE] | Any AE | 103 participants |
| Teriflunomide 7 mg | Core Treatment Period: Overview of Adverse Events [AE] | - Any serious AE | 12 participants |
| Teriflunomide 7 mg | Core Treatment Period: Overview of Adverse Events [AE] | - Any AE leading to death | 0 participants |
| Teriflunomide 7 mg | Core Treatment Period: Overview of Adverse Events [AE] | - Any AE leading to treatment discontinuation | 9 participants |
| Teriflunomide 14 mg | Core Treatment Period: Overview of Adverse Events [AE] | - Any AE leading to treatment discontinuation | 12 participants |
| Teriflunomide 14 mg | Core Treatment Period: Overview of Adverse Events [AE] | Any AE | 102 participants |
| Teriflunomide 14 mg | Core Treatment Period: Overview of Adverse Events [AE] | - Any AE leading to death | 0 participants |
| Teriflunomide 14 mg | Core Treatment Period: Overview of Adverse Events [AE] | - Any serious AE | 6 participants |
| IFN-β-1a | Core Treatment Period: Overview of Adverse Events [AE] | - Any AE leading to treatment discontinuation | 22 participants |
| IFN-β-1a | Core Treatment Period: Overview of Adverse Events [AE] | - Any serious AE | 7 participants |
| IFN-β-1a | Core Treatment Period: Overview of Adverse Events [AE] | - Any AE leading to death | 0 participants |
| IFN-β-1a | Core Treatment Period: Overview of Adverse Events [AE] | Any AE | 97 participants |
Secondary
Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores
TSQM version 1.4 is an instrument to assess patients' satisfaction with medication. It consists of 13 questions that cover three dimensions (effectiveness, side effects and convenience) plus a global satisfaction question. Four scores ranging from 0 to 100 (extremely satisfied) are obtained. Least-square means were estimated using a Mixed-effect model with repeated measures \[MMRM\] on TSQM score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction as factors).
Time frame: 48 weeks
Population: ITT population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Teriflunomide 7 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Effectivness score | 67.25 units on a scale | Standard Error 2.7 |
| Teriflunomide 7 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Side effects score | 95.29 units on a scale | Standard Error 2.31 |
| Teriflunomide 7 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Convenience score | 88.30 units on a scale | Standard Error 1.97 |
| Teriflunomide 7 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Global satisfaction score | 68.29 units on a scale | Standard Error 2.77 |
| Teriflunomide 14 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Global satisfaction score | 68.82 units on a scale | Standard Error 2.78 |
| Teriflunomide 14 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Effectivness score | 63.13 units on a scale | Standard Error 2.75 |
| Teriflunomide 14 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Convenience score | 89.85 units on a scale | Standard Error 1.98 |
| Teriflunomide 14 mg | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Side effects score | 93.15 units on a scale | Standard Error 2.34 |
| IFN-β-1a | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Global satisfaction score | 60.98 units on a scale | Standard Error 2.94 |
| IFN-β-1a | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Side effects score | 71.38 units on a scale | Standard Error 2.5 |
| IFN-β-1a | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Convenience score | 61.90 units on a scale | Standard Error 2.11 |
| IFN-β-1a | Core Treatment Period: Treatment Satisfaction Questionnaire for Medication [TSQM] Scores | Effectivness score | 59.30 units on a scale | Standard Error 2.97 |
Secondary
Extension Treatment Period: ARR Poisson Regression Estimates
ARR was obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of the standardized treatment durations.To account for the different treatment durations among participants, a Poisson Regression Model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as offset variable; treatment group, region of enrolment and baseline EDSS stratum as covariates).
Time frame: Extension treatment period (Maximum: 197 weeks)
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teriflunomide 7 mg | Extension Treatment Period: ARR Poisson Regression Estimates | 0.236 relapses per year |
| Teriflunomide 14 mg | Extension Treatment Period: ARR Poisson Regression Estimates | 0.193 relapses per year |
| IFN-β-1a | Extension Treatment Period: ARR Poisson Regression Estimates | 0.252 relapses per year |
Secondary
Extension Treatment Period: Overview of AEs
AEs were any unfavourable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time frame: From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period
Population: Safety population. Participants were considered in the treatment group to which they were randomized regardless of the drug they actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Teriflunomide 7 mg | Extension Treatment Period: Overview of AEs | Any serious AE | 9 participants |
| Teriflunomide 7 mg | Extension Treatment Period: Overview of AEs | Any AE leading to treatment discontinuation | 8 participants |
| Teriflunomide 7 mg | Extension Treatment Period: Overview of AEs | Any AE leading to death | 0 participants |
| Teriflunomide 7 mg | Extension Treatment Period: Overview of AEs | Any AE | 83 participants |
| Teriflunomide 14 mg | Extension Treatment Period: Overview of AEs | Any AE leading to death | 0 participants |
| Teriflunomide 14 mg | Extension Treatment Period: Overview of AEs | Any AE leading to treatment discontinuation | 6 participants |
| Teriflunomide 14 mg | Extension Treatment Period: Overview of AEs | Any serious AE | 13 participants |
| Teriflunomide 14 mg | Extension Treatment Period: Overview of AEs | Any AE | 76 participants |
| IFN-β-1a | Extension Treatment Period: Overview of AEs | Any AE leading to treatment discontinuation | 5 participants |
| IFN-β-1a | Extension Treatment Period: Overview of AEs | Any AE | 48 participants |
| IFN-β-1a | Extension Treatment Period: Overview of AEs | Any AE leading to death | 0 participants |
| IFN-β-1a | Extension Treatment Period: Overview of AEs | Any serious AE | 12 participants |