A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 1,131
- 试验地点
- 306
- 主要终点
- Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS)
研究概览
简要总结
Primary Objective:
To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS
Secondary Objective:
To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites in NRSPMS and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168
详细描述
This was an event-driven (6-month CDP) trial with a variable treatment duration (end-of-study [EOS] duration: up to approximately 47months).
Participants with 6-month confirmed disability progression (CDP) had an option to receive tolebrutinib in the open-label (OL).
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 60 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 of oral SAR442168 once daily
干预措施: Tolebrutinib (Drug)
Placebo
Placebo tablet to match SAR442168 once daily
干预措施: Placebo to match Tolebrutinib (Drug)
结局指标
主要结局
Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS)
时间窗: Baseline (Day 1) up to approximately 47 months
The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal \[motor\], cerebellar \[coordination\], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 6-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score of \>=1.0 point from the baseline EDSS score when the baseline score was \<=5.0 or of \>=0.5 points when the baseline EDSS score was \>5.0 confirmed after a minimum 6-month interval.
次要结局
- Time to Onset of 3-month Confirmed Disability Progression as Assessed by Expanded Disability Status Scale(Baseline (Day 1) up to approximately 47 months)
- Mean Number of New and/or Enlarging T2-hyperintense Lesions Per Year(Baseline (Day 1) up to approximately 47 months)
- Time to Onset of Sustained 20% Increase in the 9-hole Peg Test (HPT) for at Least 3 Months(Baseline (Day 1) up to approximately 47 months)
- 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 47 months))
- Time to Onset of Sustained 20% Increase in the Timed 25-foot Walk (T25-FW) for at Least 3 Months(Baseline (Day 1) up to approximately 47 months)
- Time to Onset of 6-month Confirmed Disability Improvement (CDI) as Assessed by Expanded Disability Status Scale(Baseline (Day 1) up to approximately 47 months)
- Percent Change in Brain Volume at EOS Compared to Month 6(Month 6 to EOS (up to approximately 47 months))
- Change From Baseline in Cognitive Function as Assessed by Symbol Digit Modalities Test (SDMT) at EOS(Baseline (Day 1) to EOS (up to approximately 47 months))
- Change From Baseline in Cognitive Function as Assessed by California Verbal Learning Test Second Edition (CVLT-II) at EOS(Baseline (Day 1) to EOS (up to approximately 47 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 47 months))
- Number of Participants With Treatment-emergent Adverse Events (AEs), Treatment-emergent Serious AEs, Treatment-emergent AEs 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 end of follow-up, up to approximately 47 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 Cluster of Differentiation (CD)19+ B Cells at EOS(Baseline (Day 1) to EOS (up to approximately 47 months))
- Change From Baseline in Serum Immunoglobulin (Ig) Levels at EOS(Baseline (Day 1) to EOS (up to approximately 47 months))