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
Study of an Investigational Medication in Relapsing Multiple Sclerosis
Ajay Gupta
Primary Investigator
Brief description of study
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.
Detailed description of study
Participants will be randomly assigned with a 1:1 ratio to frexalimab IV q4w 1200 mg as well as a placebo to match the teriflunomide tablet daily or to 14 mg oral teriflunomide daily as well as
a placebo administered IV q4w to match frexalimab IV q4w. Randomization will be stratified by the EDSS score at screening (non-US) within each study.
Study details include:
- This event-driven study will have variable duration of approximately 40 months for the first participant being randomized and approximately 20 months for the last participant randomized.
- The study intervention duration will vary ranging from approximately 12 to 40 months.
- The assessment of scheduled visits will include 1 common end of study [EOS] visit and 3 follow-up visits) with a visit frequency of every 4 weeks for the first 6 months and then every 3 months.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Relapsing Multiple Sclerosis, RMS
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Age: 18 years - 55 years
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Gender: All
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- History or current hypogammaglobulinemia defined by values below the lower limit of normal (LLN).
- 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 purpose of this study is to compare the effectiveness and safety of an investigational medication to an existing treatment in adults with relapsing forms of multiple sclerosis (MS). Multiple sclerosis is a condition where the immune system mistakenly attacks the protective covering of nerves, leading to communication problems between the brain and the rest of the body. This study involves participants aged 18 to 55 years who have been diagnosed with relapsing forms of MS.
Participants will be randomly assigned to receive either the investigational medication through an intravenous (IV) infusion every four weeks or a daily oral dose of the existing treatment, with a placebo to match the alternate treatment. This double-blind study means neither the participants nor the researchers will know who receives which treatment. The study includes regular visits for assessments, beginning with more frequent visits every four weeks for the first six months, then every three months thereafter.
- Who can participate: Adults aged 18 to 55 with relapsing multiple sclerosis, as per the 2017 McDonald diagnostic criteria, and an EDSS score of 5.5 or less can participate. Key criteria include having had at least one relapse in the past year or specific MRI findings.
- Study details: Participants will be randomly assigned to receive either the investigational medication or a placebo, which is an inactive substance that looks like the investigational medicine but does not contain any medicine. They will also receive the existing treatment or a matching placebo.
