Master Protocol of Two Independent, Randomized, Double-blind, Phase 3 Studies Comparing Efficacy and Safety of Frexalimab (SAR441344) to Teriflunomide in Adult Participants With Relapsing Forms of Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 1,655
- 试验地点
- 763
- 主要终点
- Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses
研究概览
简要总结
The purpose of each study is to independently measure the annualized relapse rate (ARR) with administration of frexalimab compared to a daily oral dose of teriflunomide in male and female participants with relapsing forms of multiple sclerosis (aged 18 to 55 years at the time of enrollment). People diagnosed with relapsing forms of multiple sclerosis are eligible for enrollment as long as they meet all the inclusion criteria and none of the exclusion criteria.
Study details include:
- This event-driven study will have variable duration depending on the recruitment rate, the event rate, the study discontinuation rate and the 12-month minimum treatment duration. Different participants will have different study durations. The last participant randomized will have at least 12 months of study duration, and assuming a 28-month recruitment period, the first participant randomized will have 40 months or longer of study duration.
- The study intervention duration will vary similarly as the study duration.
- The scheduled visits will include monthly visits for the first 6 months and quarterly visits thereafter until the common end of study (EOS), or premature end of treatment (pEOT) after which 3 follow-up visits will be performed
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-dummy
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
- •The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria.
- •The participant has an EDSS score ≤5.5 at the first visit (Screening Visit)
- •The participant must have at least 1 of the following prior to screening:
- •≥1 documented relapse within the previous year OR
- •≥2 documented relapses within the previous 2 years, OR
- •≥1 documented Gd enhancing lesion on an MRI scan within the previous year.
- •Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria
- •The participant has a history of infection or may be at risk for infection:
- •The presence of psychiatric disturbance or substance abuse.
- •History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment.
- •Current hypogammaglobulinemia defined by Ig levels below the LLN at Screening or a history of primary hypogammaglobulinemia.
- •A history or presence of disease that can mimic MS symptoms, such as, but not limited to neuromyelitis optica spectrum disorder, systemic lupus erythematosus, Sjogren's syndrome, acute disseminated encephalomyelitis, and myasthenia gravis.
- •The participant has had a relapse in the 30 days prior to randomization.
- •The participant has contraindication for MRI, ie, presence of pacemaker, metallic implants in high risk areas (ie, artificial heart valves, aneurysm/vessel clips), presence of metallic material (eg, shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol scheduled MRI scans.
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Frexalimab
Participants will receive Frexalimab infusion and placebo tablet.
干预措施: Activated charcoal (Drug)
Frexalimab
Participants will receive Frexalimab infusion and placebo tablet.
干预措施: Cholestyramine (Drug)
Teriflunomide
Participants will receive teriflunomide tablet and placebo infusion.
干预措施: Cholestyramine (Drug)
Frexalimab
Participants will receive Frexalimab infusion and placebo tablet.
干预措施: MRI contrast-enhancing agents (Drug)
Frexalimab
Participants will receive Frexalimab infusion and placebo tablet.
干预措施: Placebo tablet (Drug)
Frexalimab
Participants will receive Frexalimab infusion and placebo tablet.
干预措施: Frexalimab (Drug)
Teriflunomide
Participants will receive teriflunomide tablet and placebo infusion.
干预措施: Placebo infusion (Drug)
Teriflunomide
Participants will receive teriflunomide tablet and placebo infusion.
干预措施: MRI contrast-enhancing agents (Drug)
Teriflunomide
Participants will receive teriflunomide tablet and placebo infusion.
干预措施: Teriflunomide (Drug)
Teriflunomide
Participants will receive teriflunomide tablet and placebo infusion.
干预措施: Activated charcoal (Drug)
结局指标
主要结局
Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses
时间窗: Until Week 156
ARR during the study period assessed by protocol-defined adjudicated relapses. This endpoint will be analyzed in the ITT population of each study using a negative binomial model with the total number of adjudicated relapses per participant occurring during the observation period as the response variable and with terms for treatment group, Gd-enhancing T1 lesions at baseline (presence, absence), EDSS strata (\<4, ≥4), and geographical region (US, non-US).
次要结局
- Time to onset of composite confirmed disability worsening (cCDW)(Until Week 156)
- Time to onset of cCDW, confirmed over 3 months(Until Week 156)
- Time to onset of individual components of the composite, confirmed over 3-months or 6-months(Until Week 156)
- Time to onset of confirmed disability improvement (CDI)(Until Week 156)
- Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI(Until Week 156)
- Total number of new Gd-enhancing T1hyperintense lesions per scan as detected by MRI(Until Week 156)
- Percent change in brain volume loss as detected by brain MRI scans at the EOS compared to Month 6(From Week 24 to Week 156)
- Change in cognitive function at the EOS compared to baseline as assessed by the symbol digit modalities test (SDMT)(From baseline to Week 156)
- Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time(From baseline to Week 156)
- Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time(Until Week 156)
- Number of participants with adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs and safety scales during the study period(Until Week 168)
- Number of participants with potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG and vital signs during the study period(Until Week 168)
- Number of participants with antidrug (ADAs) over time(Until Week 156)
- Change from baseline in plasma neurofilament light chain (NfL) levels over time(Until Week 144)
- Frexalimab plasma concentration over time(Until Week 144)
- Progression independent of relapse activity defined as the time to onset of 6-month cCDW(Until Week 156)