A randomized, double-blind, double-dummy, parallel-groupstudy, comparing the efficacy and safety of remibrutinibversus teriflunomide in participants with relapsing multiplesclerosis, followed by extended treatment with open-labelremibrutinib
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 800
- 试验地点
- 9
- 主要终点
- To demonstrate that remibrutinib (100 mg b.i.d. p.o.) is superior to teriflunomide (14 mg q.d. p.o.) in reducing the frequency of confirmed relapses
研究概览
简要总结
The purpose of the study is to provide efficacy,safety and tolerability data for remibrutinib, to support regulatory approvalworldwide as a treatment for relapsing multiple sclerosis (RMS). Two identicalPhase III trials (CLOU064C12301 and CLOU064C12302) will be conductedsimultaneously. The primary objective of this study is todemonstrate that remibrutinib issuperior to teriflunomide in reducingthe frequency of confirmed relapses.Remibrutinib has a favorable pharmacological profile in terms ofpotency, selectivity for BTK and safety (as observed in available Phase IIdata) in different indications at relevant doses and may offer a noveltherapeutic option for participants with RMS. This study consists of an initial Core Part (CP)(maximum duration per participant of up to 30 months), followed by an ExtensionPart (of up to 5 years duration) for eligible participants. The Core Part is a randomized, double-blind, double-dummy, activecomparator-controlled, fixed-dose, parallel-group, multi-center study inapproximately 800 participants with RMS. The treatment duration of the CorePart for individual participants will be variable based on when the Core PartEnd of Study (EOS) criteria are met. The maximal duration of the Core Part foran individual participant will be 30 months (~2.5 years).
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 18.00 Year(s) 至 55.00 Year(s)（—）
- 性别
- All
入选标准
- •â€¢18 to 55 years of age •Diagnosis of RMS according to the 2017 McDonald diagnostic criteria •At least: 1 documented relapse within the previous year.
- •OR 2 documented relapses within the previous 2 years, OR 1 active Gadolinium (Gd)-enhancing lesion in the 12 months.
- •â€¢EDSS score of 0 to 5.5 (inclusive) •Neurologically stable within 1 month.
排除标准
- •1-Diagnosis of primary progressive multiple sclerosis (PPMS) 2-Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening 3-History of clinically significant CNS disease other than MS 4-Ongoing substance abuse (drug or alcohol) 5-History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer), 6-Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML 7-suicidal ideation or behavior 8-Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary , renal, hepatic, endocrine, metabolic, hematological disorders or gastrointestinal disease that can interfere with interpretation of the study results or protocol adherence 9-Participants who have had a splenectomy 10-Active clinically significant systemic bacterial, viral, parasitic or fungal infections 11-Positive results for syphilis or tuberculosis testing 12-Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids 13-Active, chronic disease of the immune system (including stable disease treated with immune therapy (e.g. Leflunomide, Methotrexate)) other than MS (e.g. rheumatoid arthritis, systemic lupus erythematosus, etc.) with the exception of well-controlled diabetes or thyroid disorder.
- •14-Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody 15-History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or participants with moderate or severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease.
- •16-History of severe renal disease or creatinine level 17-Participants at risk of developing or having reactivation of hepatitis Hematology parameters at screening: 1-Hemoglobin: < 10 g/dl (<100g/L) 2-Platelets: < 100000/mm3 (<100 x 109/L) 3-Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L) 4-White blood cells: <3 000/mm3 (<3.0 x 109/L) 5-Neutrophils: < 1 500/mm3 (<1.5 x 109/L) 6-B-cell count < 50% lower limit of normal (LLN) or total IgG & total IgM < LLN (only required for participants who had a history of receiving B-cell therapies, such as rituximab, ocrelizumab or ofatumumab, prior to screening) History or current diagnosis of significant ECG abnormalities Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment (prior to randomization) Use of other investigational drugs Requirement for anticoagulant medication or use of dual anti-platelet therapy Significant bleeding risk or coagulation disorders, History of gastrointestinal bleeding Major surgery within 8 weeks prior to screening History of hypersensitivity to any of the study drugs or excipients Pregnant or nursing (lactating) female participants, prior to randomization Women of childbearing potential not using highly effective contraception Sexually active males not agreeing to use condom Have received any live or live-attenuated vaccines within 6 weeks of randomization or requirement to receive these vaccinations during study Use of strong CYP3A4 inhibitors or strong CYP3A4 inducers within two weeks prior to randomization Inclusion to Extension part: patient who complete the Core Part of the study on double-blind study treatment and conduct the Accelerated Elimination Procedure (AEP).
结局指标
主要结局
To demonstrate that remibrutinib (100 mg b.i.d. p.o.) is superior to teriflunomide (14 mg q.d. p.o.) in reducing the frequency of confirmed relapses
时间窗: Annualized relapse rate (ARR) of confirmed relapses( the number of confirmed relapses per year). Symptoms will be reported by participants at at a scheduled visit or at any other time and confirmation of relapses will be assessed by EDSS Rater
次要结局
- Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in(â— Disease-Activity-free status based on pooled data from both identical pivotal studies (MRI Cohort))
- Other secondary objectives (Core Part):(To assess the pharmacokinetics (PK) of remibrutinib)
- 1. Key secondary objectives (Core Part): To assess whether remibrutinib is superior to teriflunomide in(Reducing new inflammatory activity on MRI, based on MRI cohort data)