Proof-of-concept Study for SAR441344 (Frexalimab) in Relapsing Multiple Sclerosis

Study Overview
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Brief Summary
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Primary Objective: To determine the efficacy of SAR441344 as measured by reduction of the number of new active brain lesions Secondary Objective: To evaluate efficacy of SAR441344 on disease activity as assessed by other MRI measures To evaluate the safety and tolerability of SAR441344 To evaluate pharmacokinetics of SAR441344

Detailed Description
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The duration of each participant will be no longer than 176 weeks in both parts of the study, including 4 weeks of screening, at maximum 148 weeks of treatment and 24 weeks of follow-up.

Official Title
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A Phase 2, Double-blind, Randomized, Placebo-controlled Study Assessing Efficacy and Safety of SAR441344, a CD40L-antagonist Monoclonal Antibody, in Participants With Relapsing Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: SAR441344 IV
* Drug: placebo IV
* Drug: SAR441344 SC
* Drug: placebo SC
* Drug: MRI contrast-enhancing preparations


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent. The participant must have been diagnosed with RMS (relapsing-remitting MS and secondary progressive MS participants with relapses) according to the 2017 revision of the McDonald diagnostic criteria. The participant must have at least 1 documented relapse within the previous year, or ≥2 documented relapses within the previous 2 years, or ≥1 active Gd-enhancing brain lesion on an MRI scan in the past 6 months and prior to screening. Body weight within 45 to 120 kg (inclusive) and body mass index (BMI) within the range 18.0 to 35.0 kg/m2 (inclusive) at Screening. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Capable of giving signed informed consent. Exclusion criteria: The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria or with non-relapsing SPMS. The participant has conditions or situations that would adversely affect participation in this study. The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study. 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. Allergies to humanized monoclonal antibodies or severe post-treatment hypersensitivity reactions other than localized injection site reaction, to any biological molecule. The participant has received any of the forbidden medications/treatments within the specified time frame before any baseline assessment. The participant has taken other investigational drug within 3 months or 5-half-live, whichever is longer, before the screening visit. The participant has an EDSS score >5.5 at the first screening visit. The participant has had a relapse in the 30 days prior to randomization. Positive human immunodeficiency virus (HIV) serology (anti HIV1 and anti HIV2 antibodies) or a known history of HIV infection, active or in remission. Abnormal laboratory test(s) at Screening. Presence of Hepatitis B surface antigen (HBsAg) or anti-Hepatitis B core antibodies (anti-HBc Ab) at screening or within 3 months prior to first dose of study intervention. Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. 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: 55 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
Interventional Model Description: Part A is a 12-week, double-blind, placebo-controlled part; Part B is an open-label SAR441344 treatment part.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV SAR441344<br>SAR441344 IV | Drug: SAR441344 IV<br>* Pharmaceutical form: Solution Route of administration: IV infusion<br>Drug: MRI contrast-enhancing preparations<br>* Pharmaceutical form: Solution Route of administration: IV injection<br>|
| Placebo Comparator: IV Placebo<br>Placebo IV | Drug: placebo IV<br>* Pharmaceutical form: Solution Route of administration: IV infusion<br>Drug: MRI contrast-enhancing preparations<br>* Pharmaceutical form: Solution Route of administration: IV injection<br>|
| Experimental: SC SAR441344<br>SAR441344 SC | Drug: SAR441344 SC<br>* Pharmaceutical form: Solution Route of administration: SC injection<br>Drug: MRI contrast-enhancing preparations<br>* Pharmaceutical form: Solution Route of administration: IV injection<br>|
| Placebo Comparator: SC Placebo<br>Placebo SC | Drug: placebo SC<br>* Pharmaceutical form: Solution Route of administration: SC injection<br>Drug: MRI contrast-enhancing preparations<br>* Pharmaceutical form: Solution Route of administration: IV injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new Gadolinium (Gd)-enhancing T1-hyperintense (GdE T1) lesions | measured by brain magnetic resonance imaging (MRI) | At Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new or enlarging T2 lesions | measured by brain magnetic resonance imaging (MRI) | At Week 12 | 
| Total number of GdE T1 lesions | Total number of GdE T1 lesions at Week 12 | At Week 12 | 
| Adverse events (AEs) and serious adverse events (SAEs) | Number of participants with AEs and SAEs | Until Week 172 | 
| Antidrug antibodies (ADA) | Number of participants with ADA | Until Week 172 | 
| Pharmacokinetic (PK) parameters: Cmax | maximum concentration | Until Week 172 | 
| PK parameter: tmax | time to Cmax | Until Week 172 | 
| PK parameter: AUC0-tau | area under the curve over the dosing interval | Until Week 172 | 
| PK parameter: t1/2z | elimination half-life | Until Week 172 |