A Multi-center Double-blind Parallel-group Placebo-controlled Study of the Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis Who Are Treated With Interferon-beta
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Sanofi
- 入组人数
- 534
- 试验地点
- 185
- 主要终点
- Annualized Relapse Rate (ARR) (Poisson Regression Estimates)
研究概览
简要总结
The primary objective was to demonstrate the effect of teriflunomide, in comparison to placebo, on frequency of Multiple Sclerosis (MS) relapses in patients with relapsing forms of MS who are treated with Interferon-beta (IFN-beta).
The secondary objectives were:
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Assess the effect of teriflunomide, in comparison to placebo, when added to IFN-beta on:
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Disease activity as measured by brain Magnetic Resonance Imaging (MRI)
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Disability progression
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Burden of disease and disease progression as measured by brain MRI
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Evaluate the safety and tolerability of teriflunomide when added to IFN-beta therapy
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Assess the pharmacokinetics of teriflunomide in use in addition to baseline IFN-beta therapy
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Assess associations between variations in genes and clinical outcomes (safety and efficacy)
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Assess other measures of efficacy of teriflunomide such as fatigue and health-related quality of life
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Assess measures of health economics (hospitalization due to relapse, including the length of stay and any admission to intensive care unit)
详细描述
The study period per patient was expected to be between 56 and 160 weeks depending on when the patient was randomized and this included the following:
- a screening period up to 4 weeks,
- a treatment period expected to be between 48 and 152 weeks,
- 4-week post rapid elimination follow-up period.
Patients were to continue on treatment until a fixed common end date which was approximately 48 weeks after randomization of the last patient.
For those patients who completed the treatment period, a long term extension study of approximately 1 year (including teriflunomide alone) was initially planned to be proposed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Teriflunomide 7 mg + IFN-beta
Teriflunomide 7 milligram (mg) once a day concomitantly with IFN-beta therapy.
干预措施: Teriflunomide (Drug)
Teriflunomide 7 mg + IFN-beta
Teriflunomide 7 milligram (mg) once a day concomitantly with IFN-beta therapy.
干预措施: Interferon-beta (IFN-beta) (Drug)
Teriflunomide 14 mg + IFN-beta
Teriflunomide 14 mg once a day concomitantly with IFN-beta therapy.
干预措施: Teriflunomide (Drug)
Teriflunomide 14 mg + IFN-beta
Teriflunomide 14 mg once a day concomitantly with IFN-beta therapy.
干预措施: Interferon-beta (IFN-beta) (Drug)
Placebo + IFN-beta
Placebo (for teriflunomide) once a day concomitantly with IFN-beta therapy.
干预措施: Placebo (for teriflunomide) (Drug)
Placebo + IFN-beta
Placebo (for teriflunomide) once a day concomitantly with IFN-beta therapy.
干预措施: Interferon-beta (IFN-beta) (Drug)
结局指标
主要结局
Annualized Relapse Rate (ARR) (Poisson Regression Estimates)
时间窗: Up to a maximum of 108 weeks depending on time of enrollment
ARR is the total number of confirmed relapses that occurred during the treatment period divided by the total number of patient-years treated. 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. 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 IFN-beta dose stratum, and number of relapses in the year prior to randomization as covariates).
次要结局
- Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per Scan (Poisson Regression Estimates)(Up to a maximum of 108 weeks depending on time of enrollment)
- Time to 12-Week Sustained Disability Progression(Up to a maximum of 108 weeks depending on time of enrollment)
- Brain MRI Assessment: Volume of Gd-enhancing T1-lesions Per MRI Scan(Up to a maximum of 108 weeks depending on time of enrollment)
- Brain MRI Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) at Week 24(Baseline, Week 24)
- Time to Relapse: Kaplan-Meier Estimates of the Probability of no Relapse at Week 24, 48, and 72(Up to a maximum of 108 weeks depending on time of enrollment)
- Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 24(Baseline, Week 24)
- Change From Baseline in Short Form Generic Health Survey - 36 Items, Version 2 (SF-36v2) Summary Scores at Week 24(Baseline, Week 24)
- Resource Utilization When Relapse(Up to a maximum of 108 weeks depending on time of enrollment)
- Overview of Adverse Events (AEs)(First study drug intake up to 28 days after last study drug intake, for up to 112 weeks)