A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Fenebrutinib in Relapsing Multiple Sclerosis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 109
- 试验地点
- 30
- 主要终点
- DBT Phase: New Gadolinium (Gd) - Enhancing T1 Lesion Rate Observed on Magnetic Resonance Imaging (MRI) Scans of the Brain Over 12 Weeks
研究概览
简要总结
This is a study evaluating the effect of fenebrutinib on brain magnetic resonance imaging (MRI) in participants with RMS. The safety and pharmacokinetics of fenebrutinib will also be evaluated. Participants will be randomized to receive either fenebrutinib or placebo. This study consists of two parts: Double-blind treatment (DBT) phase and an optional Open-label extension (OLE) phase.
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)
盲法说明
Sponsor will also be blinded.
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
- •A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria.
- •Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening.
- •For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
- •For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.
排除标准
- •Disease duration of > 10 years from the onset of symptoms and an EDSS score at screening < 2.
- •Female participants who are pregnant or breastfeeding, or intending to become pregnant.
- •Male participants who intend to father a child during the study.
- •A diagnosis of Primary Progressive Multiple Sclerosis (PPMS) or non-active Secondary Progressive Multiple Sclerosis (SPMS).
- •Any known or suspected active infection at screening, including but not limited to a positive screening tests for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML).
- •History of cancer including hematologic malignancy and solid tumors within 10 years of screening.
- •Presence of other neurological disorders that could interfere with the diagnosis of MS or with the assessments of safety or efficacy during the study.
- •Clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
- •Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
- •History of alcohol or other drug abuse within 12 months prior to screening.
- •History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection.
- •Inability to complete an MRI scan.
- •Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening.
- •Receipt of a live-attenuated vaccine within 6 weeks prior to randomization.
- •Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.
研究组 & 干预措施
Placebo
Participants will receive oral placebo.
干预措施: Placebo (Drug)
Fenebrutinib
Participants will receive oral fenebrutinib.
干预措施: Fenebrutinib (Drug)
结局指标
主要结局
DBT Phase: New Gadolinium (Gd) - Enhancing T1 Lesion Rate Observed on Magnetic Resonance Imaging (MRI) Scans of the Brain Over 12 Weeks
时间窗: MRI scans performed at Weeks 4, 8 and 12
Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Weeks 4, 8, and 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The total number of new Gd-enhancing T1 lesions were calculated as the sum of the individual number of new lesions observed at Weeks 4, 8 and 12. The lesion rate (new lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.
次要结局
- DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain Over 12 Weeks(MRI scans performed at Weeks 4, 8 and 12)
- DBT Phase: Proportion of Participants Free From Any New Gd - Enhancing T1 Lesions and New or Enlarging T2 - Weighted Lesions Observed on MRI Scans of the Brain Over 12 Weeks(MRI scans performed at Weeks 4, 8 and 12)
- DBT Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to Week 12)
- OLE Phase: Number of Participants With AEs and SAEs(OLE Baseline (DBT Week 12) up to Week 192)
- Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)(Up to Week 192)
- Plasma Concentrations of Fenebrutinib at Specified Timepoints(Up to Week 192)