A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Remibrutinib in Patients With Secondary Progressive Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,275
- 试验地点
- 266
- 主要终点
- Time to 6-month confirmed disability progression (6mCDP) on Expanded Disability Status Scale (EDSS)
研究概览
简要总结
The purpose of this study is to provide efficacy and safety data for remibrutinib in patients with secondary progressive multiple sclerosis (SPMS)
详细描述
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, parallel-group, event-driven study to evaluate the efficacy, safety and tolerability of remibrutinib in SPMS patients. Approximately 1275 eligible participants will be randomized to receive either remibrutinib or matching placebo.
The study consists of an event-driven Core Part with double-blind treatment, followed by an Extension Part with open-label remibrutinib treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind on Core part and Open label on Extension part
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to any assessment performed.
- •Male or female participants aged 18-65 (inclusive) at Screening.
- •Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al 2018), with current SPMS in accordance with the revised clinical course (Lublin et al 2014) at Screening
- •Absence of documented clinical relapses in the 24 months before Screening and randomization.
- •EDSS score of 3.0 to 6.0 (inclusive) at Screening.
- •Documented evidence of disability progression in the 12 months before Screening.
排除标准
- •Unwilling or unable to undergo MRI scans as per protocol (for example, claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator)).
- •History of clinically significant central nervous system (CNS) disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic multiple sclerosis (MS).
- •Ongoing substance abuse (drug or alcohol) or any other factor (e.g. serious psychiatric condition) that may interfere with the participant's ability to cooperate and comply with the study procedures.
- •Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or neurological symptoms consistent with PML.
- •Women of childbearing potential (WOCBP), unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for at least 1 week after stopping study treatment.
- •Significant bleeding risk or coagulation disorders, at Screening.
- •Use of exclusionary medication prior to Screening/randomization as listed in the protocol.
- •Other protocol-defined inclusion/exclusion critria may apply
研究组 & 干预措施
Placebo
Core Part: Matching placebo film-coated tablet taken orally
[Extension Part: Open-label remibrutinib film-coated tablet taken orally]
干预措施: Placebo (Drug)
Remibrutinib (LOU064)
Core Part: Remibrutinib film-coated tablet taken orally
[Extension Part: Open-label remibrutinib film-coated tablet taken orally]
干预措施: Remibrutinib (Open label) (Drug)
Placebo
Core Part: Matching placebo film-coated tablet taken orally
[Extension Part: Open-label remibrutinib film-coated tablet taken orally]
干预措施: Remibrutinib (Open label) (Drug)
Remibrutinib (LOU064)
Core Part: Remibrutinib film-coated tablet taken orally
[Extension Part: Open-label remibrutinib film-coated tablet taken orally]
干预措施: Remibrutinib (blinded) (Drug)
结局指标
主要结局
Time to 6-month confirmed disability progression (6mCDP) on Expanded Disability Status Scale (EDSS)
时间窗: From baseline up to approximately 5 years
The EDSS is an ordinal scale used for assessing neurologic impairment in MS based on a neurological examination. It consists of scores in each of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). 6mCDP is defined as an increase from baseline in EDSS sustained for at least 6 months.
次要结局
- Time to 3-month confirmed disability progression (3mCDP) on EDSS(From baseline up to approximately 5 years)
- Time to 6-month confirmed disability improvement (6mCDI) on EDSS(From baseline up to approximately 5 years)
- Time to 3-month worsening by at least 20% in Timed 25-Foot Walk (T25FW)(From baseline up to approximately 5 years)
- Time to 3-month worsening by at least 20% in 9-Hole Peg Test (9-HPT)(From baseline up to approximately 5 years)
- Annualized rate of new or enlarging T2 lesions(From baseline up to approximately 5 years)
- Annualized rate of brain atrophy(From baseline up to approximately 5 years)
- Time to 6-month worsening by at least 4 points in Symbol Digit Modalities Test (SDMT)(From baseline up to approximately 5 years)
- Number of participants with Adverse events and Serious adverse events (SAE)(From baseline up to approximately 5 years)