Efficacy and Safety Study of Frexalimab (SAR441344) in Adults With Nonrelapsing Secondary Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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The purpose of this randomized, double-blind, placebo-controlled, parallel group study is to determine the efficacy of frexalimab in delaying the disability progression and the safety up to approximately 51 months administration of study intervention compared to placebo in male and female participants with nrSPMS (aged 18 to 60 years at the time of enrollment). People diagnosed with nrSPMS 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 ranging from approximately 27 to 51 months. The study intervention duration will vary ranging from approximately 27 to 51 months. The number of scheduled visits will be up to 27 (including 3 follow-up visits) with a visit frequency of every month for the first 6 months and then every 3 months.

Official Title
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A Randomized, Double-blind, Phase 3 Study Comparing Efficacy and Safety of Frexalimab (SAR441344) to Placebo in Adult Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Frexalimab
* Drug: Placebo
* Drug: MRI contrast-enhancing agents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have a previous diagnosis of RRMS in accordance with the 2017 revised McDonald criteria. Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013 endorsed by an Adjudication Committee. Participant must have documented evidence of disability progression observed during the 12 months before screening. Eligibility will be analyzed by an Adjudication Committee. Absence of clinical relapses for at least 24 months. The participant must have an EDSS score at screening from 3.0 to 6.5 points, inclusive. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Exclusion 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. 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 sensitivity to any of the study interventions, or components thereof, or has a drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. The participant was previously exposed to frexalimab. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Frexalimab<br>Frexalimab IV administration | Drug: Frexalimab<br>* SAR441344 Solution for IV infusion<br>Drug: MRI contrast-enhancing agents<br>* IV, as per respective label<br>|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br>* Solution for IV infusion<br>Drug: MRI contrast-enhancing agents<br>* IV, as per respective label<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of composite confirmed disability progression (cCDP) confirmed over 6 months | Defined as Increase from the baseline expanded disability status scale (EDSS) score of ≥1.0 point when the baseline is <5.5, or ≥0.5 point when the baseline is ≥5.5, OR Increase of ≥20% from the baseline time in the 9 hole peg test (9HPT),OR Increase of ≥20% from the baseline time in the timed 25 foot walk (T25FW) test | Until Week 204 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of composite cCDP confirmed over 3 months |  | Until Week 204 | 
| Time to onset of individual components of the composite, confirmed over 3-months or 6-months |  | Until Week 204 | 
| Time to onset of confirmed disability improvement (CDI) | defined as decrease from the baseline EDSS score of ≥1.0 or ≥ 0.5 points when baseline is ≤5.5 or >5.5 points, respectively, confirmed over 6 months. | Until Week 204 | 
| Number of new and/or enlarging T2hyperintense lesions per scan as detected by MRI, and number of new and/or enlarging T2-hyperintense lesions per month |  | Until Week 204 | 
| Percent change in brain volume loss as detected by MRI scans at the end of study (EOS) compared to Month 6 |  | From Week 24 to Week 204 | 
| Change in cognitive function at the EOS compared to baseline as assessed by symbol digit modalities test (SDMT) |  | Baseline, Until Week 204 | 
| Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time |  | Baseline, Until Week 204 | 
| Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue multiple sclerosis (MS)-8a over time |  | Baseline, Until Week 204 | 
| Annualized relapse rate during the study period assessed by protocol defined adjudicated relapses |  | Until Week 204 | 
| Number of participants with adverse events, SAEs, AEs leading to permanent study intervention discontinuation and AE of special interests (AESIs) |  | Until Week 204 | 
| Number of participants with potentially clinically significant abnormalities (PCSAs) in laboratory tests, ECG, and vital signs during the study period | 12-lead ECG (electrocardiogram) will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. | Until Week 204 | 
| Number of participants with antibody over time |  | Until Week 204 | 
| Change from baseline in serum Ig levels over time |  | Until Week 204 | 
| Change from baseline in plasma neurofilament light chain (NfL) levels over time |  | Until Week 204 | 
| Frexalimab plasma concentration over time |  | Until Week 204 |