A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis Followed by Extended Treatment With Open-label BAF312.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,651
- 试验地点
- 1
- 主要终点
- Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)
研究概览
简要总结
Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with secondary progressive multiple sclerosis (Core Part) followed by extended treatment with open-label BAF312 to obtain data on long-term safety, tolerability and efficacy (Extension Part).
详细描述
This study had two parts, a Core Part and an Extension Part. The Core Part of the study was a randomized, multicenter, double-blind, placebo-controlled parallel-group study in patients with secondary progressive multiple sclerosis (SPMS). Eligible patients were randomized (2:1) to receive either siponimod or placebo. The duration of the Core Part of the study was variable for each patient, given that this was an event-driven study and terminated when a pre-defined number of confirmed disability progression (CDP) events had occurred irrespective of duration of individual patient participation. Patients who had 6-month CDP during the Treatment Epoch of the Core Part were provided with options that included starting treatment with open label siponimod as rescue medication.
Patients who were eligible to enter the Extension Part received open label siponimod.
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
- Double (Participant, Investigator)
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
- •Prior history of relapsing remitting MS
- •SPMS defined as progressive increase of disability over at least 6 months
- •EDSS score of 3.0 to 6.5
- •No relapse of corticosteroid treatment within 3 months
排除标准
- •Women of child bearing potential must use reliable forms of contraception.
- •Diagnosis of Macular edema during screening period
- •Any medically unstable condition determined by investigator.
- •Unable to undergo MRI scans
- •Hypersensitivity to any study drugs or drugs of similar class
研究组 & 干预措施
Siponimod (BAF312)
Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on the treatment epoch for 3 months. During the Core Part of the study, participants participated in a maximum of 3 epochs. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312.
干预措施: BAF312 (Drug)
Placebo
Matching placebo to BAF312 was administered orally during the Core Part of the trial. Following the Core Part, eligible participants enter the Extension Part during which all receive open-label BAF312.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)
时间窗: Baseline, every 3 month up to the maximum of approximately 3 years
The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). 3-month confirmed disability progression is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5 sustained for at least 3 months.
次要结局
- Percentage of Participants With 3-month Confirmed Worsening in T25W of at Least 20% From Baseline(Baseline, every 3 months up to the maximum of approximately 3 years)
- Percentage of Patients With Relapse (Confirmed Relapse and Any Relapse)(Up to maximum approximately 3 years)
- Change From Baseline in T2 Lesion Volume(Baseline, Month 12 and Month 24)
- Number of T1 Gd-enhancing Lesions Per Patient Per Scan(Baseline, Month 12 and Month 24)
- Percentage of Participants With 6-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)(Baseline, every 3 months up to the maximum of approximately 3 years)
- Annualized Relapse Rate (ARR) for Confirmed Relapses(Up to maximum approximately 3 years)
- Number of New or Enlarging T2 Lesions Per Patient Per Year(Baseline, Month 12 and Month 24)
- Percentage of Participants With First Relapse Events as Measured by Time to First Confirmed Relapse(Up to maximum approximately 3 years)
- Change From Baseline in MSWS-12 Converted Score(Baseline, Month 12 and Month 24)
- Percent Brain Volume Change (PBVC) Relative to Baseline(Baseline, Month 12 and Month 24)
- Number of Participants With 3-month CDP Events as Measured by EDSS in the Subgroup of SPMS Patients With/Without Superimposed Relapses(Baseline, every 3 months up to the maximum of approximately 3 years)
- Number of Participants With 3-month CDP Events as Measured by EDSS in the Subgroup of Rapidly and Not Rapidly Evolving Patients(Baseline, every 3 months up to the maximum of approximately 3 years)
- Number of Participants With 3-month CDP Events as Measured by EDSS in the Subgroup of Patients With and Without Moderate/Severe Disease Course(Baseline, every 3 months up to the maximum of approximately 3 years)