NCT05156281进行中（未招募）3 期
A Randomized, Double-blind, Double-dummy, Parallel-group Study, Comparing the Efficacy and Safety of Remibrutinib Versus Teriflunomide in Participants With Relapsing Multiple Sclerosis, Followed by Extended Treatment With Open-label Remibrutinib
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,007
- 试验地点
- 284
- 主要终点
- Annualized relapse rate (ARR) of confirmed relapses [Core Part]
研究概览
简要总结
To compare the efficacy and safety of remibrutinib versus teriflunomide in patients with relapsing multiple sclerosis (RMS)
详细描述
The study CLOU064C12302 consists of an initial Core Part (CP) (maximum duration per participant of up to 30 months), followed by an Extension Part (EP, of up to 5 years duration) for eligible participants.
The Core Part is a randomized, double-blind, double-dummy, active comparator-controlled, fixed-dose, parallel-group, multi-center study in approximately 800 participants with relapsing multiple sclerosis (RMS).
The Extension Part is an open-label, single-arm, fixed-dose design in which eligible participants are treated with remibrutinib for up to 5 years.
A second study of identical design (CLOU064C12301) will be conducted simultaneously. Both studies will be conducted globally and data from the two studies will be pooled for some of the endpoints.
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
In order to maintain blinding, a double-dummy design will be used
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
- •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.
- •EDSS score of 0 to 5.5 (inclusive)
- •Neurologically stable within 1 month
排除标准
- •Diagnosis of primary progressive multiple sclerosis (PPMS)
- •Disease duration of more than 10 years in participants with EDSS score of 2 or less at screening
- •History of clinically significant CNS disease other than MS
- •Ongoing substance abuse (drug or alcohol)
- •History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer),
- •Participants with history of confirmed Progressive Multifocal Leukoencephalopathy (PML) or Neurological symptoms consistent with PML
- •suicidal ideation or behavior
- •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
- •Participants who have had a splenectomy
- •Active clinically significant systemic bacterial, viral, parasitic or fungal infections
- •Positive results for syphilis or tuberculosis testing
- •Uncontrolled disease states, such as asthma, or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
- •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.
- •Participants with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug induced immune deficiency), or tested positive for HIV antibody
- •History or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis (including all Child-Pugh classes) or hepatic failure or any chronic liver or biliary disease.
- •History of severe renal disease or creatinine level
- •Participants at risk of developing or having reactivation of hepatitis
- •Hematology parameters at screening:
- •Hemoglobin: < 10 g/dl (<100g/L)
- •Platelets: < 100000/mm3 (<100 x 109/L)
- •Absolute lymphocyte count < 800/mm3 (<0.8 x 109/L)
- •White blood cells: <3 000/mm3 (<3.0 x 109/L)
- •Neutrophils: < 1 500/mm3 (<1.5 x 109/L)
- •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 as per central ECG reading at screening visit
- •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 use of moderate or strong CYP3A4 inducers within two weeks prior to randomization
- •Inclusion to Extension part:
- •Participants who complete the Core Part of the study on double-blind study treatment and conduct the Accelerated Elimination Procedure (AEP)
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
Remibrutinib - Extension
Experimental
Participants on remibrutinib in Core will continue on remibrutinib tablet
干预措施: Remibrutinib (Drug)
Remibrutinib - Extension (on teriflunomide in Core)
Experimental
Participants on teriflunomide in Core will switch to remibrutinib tablet
干预措施: Remibrutinib (Drug)
Teriflunomide - Core
Active Comparator
Teriflunomide capsule and matching placebo remibrutinib tablet
干预措施: Teriflunomide (Drug)
Remibrutinib - Core
Experimental
Remibrutinib tablet and matching placebo of teriflunomide capsule
干预措施: Remibrutinib (Drug)
结局指标
主要结局
Annualized relapse rate (ARR) of confirmed relapses [Core Part]
时间窗: From Baseline, up to 30 months
ARR is the average number of confirmed MS relapses in a year
次要结局
- Annualized rate of new or enlarging T2 lesion [Core Part](Baseline up to 30 months)
- Number of Gd-enhancing T1 lesions per MRI scan [Core Part](Baseline up to 30 months)
- Time to 6-month confirmed worsening by at least 20% in the Timed 25-foot walk test (T25FW) [Core Part] (pooled data)(Baseline, up to 30 months)
- Number of participants with Adverse events and Serious adverse events (SAE) [Extension Part](Day 1 Extension up to 5 years)
- Annualized rate of new or enlarging T2 lesion [Extension Part](Day 1 Extension up to 5 years)
- Time to 3-month confirmed disability progression (3mCDP) on Expanded Disability Status Scale (EDSS) [Core Part] (pooled data)(Baseline up to 30 months)
- Time to 6-month confirmed disability progression (6mCDP) on EDSS [Core Part] (pooled data)(Baseline up to 30 months)
- Neurofilament light chain (Nfl) [Core Part](Baseline up to 30 months)
- Percentage of participants with No Evidence of Disease Activity-3 (NEDA-3) [Core Part] (pooled data)(Baseline up to 30 months)
- Time to 3-months confirmed disability progression (3mCDP) and 6-month confirmed disability progression (6mCDP) independent of relapse activity (PIRA) [Core Part] (pooled data)(Baseline up to 30 months)
- Annualized relapse rate (ARR) of confirmed relapses [Extension Part](Day 1 Extension up to 5 years)
- Time to first confirmed relapse [Core Part](Baseline up to 30 months)
- Time to 6-month confirmed disability improvement (6mCDI) on EDSS [Core Part] (pooled data)(Baseline up to 30 months)
- Change from Baseline in T2 lesion volume [Core Part](Baseline up to 30 months)
- Pharmacokinetics of remibrutinib [Core Part](Month 1, Month 6)
- Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29) [Extension Part](Day 1 Extension up to 5 years)
- Time to 6-month confirmed worsening by at least 20% in the Timed 9-hole peg test (9HPT) (pooled data) [Core Part] (pooled data)(Baseline up to 30 months)
- Time to composite 6-month confirmed disability Progression (CDP) [Core Part] (pooled data)(Baseline up to 30 months)
- Change from baseline in the Symbol Digit Modalities Test (SDMT) [Extension Part](Day 1 Extension up to 5 years)
- Change from baseline in the Symbol Digit Modalities Test (SDMT) [Core Part] (pooled data)(Baseline up to 30 months)
- Change from baseline in Multiple Sclerosis Impact Scale (MSIS-29) [Core Part](Baseline up to 30 months)
- Number of participants with Adverse events and Serious adverse events(SAE) [Core Part](Baseline up to 30 months)
- Time to 6-month confirmed disability progression (6mCDP) on EDSS [Extension Part](Day 1 Extension up to 5 years)
- Neurofilament light chain (NfL) [Extension Part](Day 1 Extension up to 5 years)
研究者
研究点 (284)
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