A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Orelabrutinib in Patients With Relapsing-Remitting Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 160
- 试验地点
- 42
- 主要终点
- The cumulative number of new GdE T1 MRI brain lesions
研究概览
简要总结
This is a randomized, double-Blind, placebo-controlled Phase 2 Study of Orelabrutinib in Patients with Relapsing-Remitting Multiple Sclerosis.
详细描述
The study contains 2 parts: Core Part and an Open-label Extension (OLE) Part.
The Core Part is a randomized, double-blind, placebo-controlled, phase 2 study. Patients with RRMS will be randomly assigned to 1 of 4 treatment groups. placebo, orelabrutinib (low dose), orelabrutinib (medium dose) and orelabrutinib (high dose) at a 1:1:1:1 ratio.
The OLE part is an open-label, single treatment arm study to enroll patients who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data.All patients will receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.
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)
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
- •Are 18 to 55 years of age at the time of signing the informed consent.
- •Are diagnosed with Relapsing Remitting Multiple Sclerosis (RRMS).
- •Are neurologically stable for ≥ 30 days prior to both Screening and Baseline.
- •One or more documented relapses within the 2 years before Screening
- •Have an EDSS score of 0 to 5.5 at Screening and Baseline (Day 1)
- •Women of childbearing potential must use effective method of contraception
- •Signed and dated informed consent
- •Patient currently participating in the Core Part who has completed the end of treatment visit and will be benefit from continued treatment per investigator's assessment. (OLE Part only)
排除标准
- •Diagnosed with progressive MS.
- •Disease duration > 10 years in participants with an EDSS ≤ 2.0 at Screening and Baseline (Day 1).
- •Immunologic disorder other than MS.
- •History or current diagnosis of other neurological disorders that may mimic MS.
- •History or current diagnosis of progressive multifocal leukoencephalopathy (PML).
- •History of myocardial infarction or cerebrovascular event within 6 months prior to Screening,
- •A history of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening.
- •An episode of major depression within the last 6 months prior to Screening (clinically stable minor depression is not exclusionary).
- •History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin
- •Breastfeeding/lactating or pregnant women
- •Participants are excluded from participation in the study if taken prohibited medications/treatments.
- •Participation in any investigational drug study within 6 months or 5 half-lives of the investigational drug, whichever is longest, prior to Screening.
- •Permanent discontinuation from the Core Part due to AE/ SAE or abnormal abnormalities or conditions leading to permanent study drug discontinuation. (OLE Part only)
- •Patient who has new abnormality appeared in the Core Part. (OLE Part only)
- •Any significant change in the subject's medical history that would preclude administration of the study drug. (OLE Part only)
- •Clinically significant laboratory abnormalities from the most recently available test in the Core Part that would preclude administration of the study drug. (OLE Part only)
研究组 & 干预措施
orelabrutinib(low dose)
The Core Part：Participants receive low dose orelabrutinib
The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.
干预措施: orelabrutinib (Drug)
placebo
The Core Part：Participants receive placebo
The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.
干预措施: placebo (Other)
placebo
The Core Part：Participants receive placebo
The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.
干预措施: orelabrutinib (Drug)
orelabrutinib(medium dose)
The Core Part ：Participants receive medium dose orelabrutinib
The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.
干预措施: orelabrutinib (Drug)
orelabrutinib (high dose)
The Core Part：Participants receive high dose orelabrutinib
The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.
干预措施: orelabrutinib (Drug)
结局指标
主要结局
The cumulative number of new GdE T1 MRI brain lesions
时间窗: up to 120 weeks
To evaluate the efficacy of orelabrutinib on the cumulative number of new gadolinium-enhancing (GdE) T1 magnetic resonance (MRI) brain lesions versus placebo over 12 weeks of treatment.
次要结局
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability ](up to 120 weeks)
- ARR[efficacy](up to 120 weeks)