A Phase 3, Randomized, Double-blind Efficacy and Safety Study Comparing SAR442168 to Teriflunomide (Aubagio®) in Participants With Relapsing Forms of Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 900
- 试验地点
- 179
- 主要终点
- Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses
研究概览
简要总结
Primary Objective:
To assess efficacy of daily SAR442168 compared to a daily dose of 14 mg teriflunomide (Aubagio) measured by annualized adjudicated relapse rate (ARR) in participants with relapsing forms of MS
Secondary Objective:
To assess efficacy of SAR442168 compared to teriflunomide (Aubagio) on disability progression, MRI lesions, cognitive performance and quality of life To evaluate the safety and tolerability of daily SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168
详细描述
This was an event-driven (6-month confirmed disability worsening [CDW]) trial with a variable treatment duration (end-of-study [EOS] duration: up to approximately 48 months).
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
SAR442168
60 mg oral SAR442168 + placebo to match the teriflunomide tablet once daily
干预措施: Tolebrutinib (Drug)
SAR442168
60 mg oral SAR442168 + placebo to match the teriflunomide tablet once daily
干预措施: Placebo to match Teriflunomide (Drug)
Teriflunomide
14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily
干预措施: Teriflunomide (Drug)
Teriflunomide
14 mg oral teriflunomide + placebo to match the SAR442168 tablet once daily
干预措施: Placebo to match Tolebrutinib (Drug)
结局指标
主要结局
Annualized Relapse Rate (ARR) as Assessed by Confirmed Protocol-defined Adjudicated Relapses
时间窗: Baseline (Day 1) to approximately 48 months
Multiple sclerosis (MS) relapse was defined as a monophasic, acute or subacute onset of new neurological symptoms or worsening of previous neurological symptoms with an objective change on neurological examination. Symptoms were attributable to MS, lasted for \>=24 hours with or without recovery, present at normal body temperature, and preceded by \>=30 days of clinical stability.
次要结局
- Time to Onset of 6-Month Confirmed Disability Worsening as Assessed by Expanded Disability Status Scale(Baseline (Day 1) to approximately 48 months)
- Time to Onset of 3-Month Confirmed Disability Worsening as Assessed by Expanded Disability Status Scale(Baseline (Day 1) to approximately 48 months)
- Mean Number of New and/or Enlarging T2-Hyperintense Lesions Per Year(Baseline (Day 1) to approximately 48 months)
- Mean Number of New Gadolinium-Enhancing T1-Hyperintense Lesions Per Scan(Baseline (Day 1) to approximately 48 months)
- Change From Baseline in Cognitive Function as Assessed by the Symbol Digit Modalities Test (SDMT) at EOS(Baseline (Day 1) to EOS (up to approximately 48 months))
- Change From Baseline in Cognitive Function as Assessed by the California Verbal Learning Test Second Edition (CVLT-II) at EOS(Baseline (Day 1) to EOS (up to approximately 48 months))
- Time to Onset of 6-Month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale(Baseline (Day 1) to approximately 48 months)
- Percent Change in Brain Volume Loss at EOS Compared to Month 6(Month 6 to EOS (up to approximately 48 months))
- Change From Baseline in Multiple Sclerosis Quality of Life 54 (MSQoL-54) Questionnaire Score at EOS(Baseline (Day 1) to EOS (up to approximately 48 months))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), TEAEs Leading to Permanent Study Intervention Discontinuation and Treatment-emergent Adverse Events of Special Interest (AESIs)(From first dose of study intervention (Day 1) up to the earliest of either 10 days post last dose, death or last contact; up to approximately 48 months)
- Maximum Observed Plasma Concentration (Cmax) of Tolebrutinib and M2 Metabolite(30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12)
- Time to Maximum Observed Plasma Concentration (Tmax) of Tolebrutinib and M2 Metabolite(30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12)
- Area Under the Plasma Concentration-time Curve Over the Last 24-hours Dosing Interval (AUC0-24) of Tolebrutinib and M2 Metabolite(30-90 minutes post-dose at Months 6, 9, and 12 and 2.5-5 hours post-dose at Months 6 and 12)
- Change From Baseline in Plasma Neurofilament Light Chain (NfL) and Serum Chitinase-3 Like Protein-1 (Chi3L1) Levels at EOS(Baseline (Day 1) to EOS (up to approximately 48 months))
- Change From Baseline in Cluster of Differentiation (CD)19+ B Cells at EOS(Baseline (Day 1) to EOS (up to approximately 48 months))
- Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS(Baseline (Day 1) to EOS (up to approximately 48 months))