Long Term Safety and Efficacy Study of Tolebrutinib (SAR442168) in Participants With Relapsing Multiple Sclerosis

Study Overview
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Brief Summary
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Primary Objective: To determine the long-term safety and tolerability of SAR442168 in RMS participants Secondary Objective: To evaluate efficacy of SAR442168 on disease activity, assessed by clinical and imaging methods

Detailed Description
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Approximately 62 months including the 8 weeks post-treatment visit

Official Title
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Long-term Extension Safety and Efficacy Study of SAR442168 in Participants With Relapsing Multiple Sclerosis

Conditions
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Relapsing Multiple Sclerosis

Intervention / Treatment
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* Drug: Tolebrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants must have completed treatment in the DRI15928 study Female participants must continue to use an acceptable effective contraception method of birth control from inclusion and until the last dose of study drug, except if she has undergone sterilization at least 3 months earlier or is postmenopausal. Menopause is defined as being amenorrheic for ≥12 months with plasma follicle stimulating hormone (FSH) level >30 UI/L. The participant must have given written informed consent prior to undertaking any study related procedure. Exclusion criteria: The participant has a confirmed concomitant laboratory or ECG abnormality or medical condition deemed by the investigator incompatible with continuation of SAR442168 treatment. The participant has received any live (attenuated) vaccine (including but not limited to varicella zoster, oral polio, and nasal influenza) between the last DRI15928 visit and the first treatment visit in the LTS16004 study. The participant has received a non-study MS disease modifying treatment between the last IMP treatment in Study DRI15928 and inclusion in Study LTS16004, which by judgement of the Investigator may add unjustified risk to switching back and continuing treatment with SAR442168. Washout periods after treatment with non-study DMTs should be respected except for interferons or glatiramer acetate treatment. The participant is receiving strong inducers or inhibitors of CYP3A or CYP2C8 hepatic enzymes. The participant is receiving anticoagulant/antiplatelet therapies, including: Acetylsalicylic acid (aspirin) Antiplatelet drugs (eg, clopidogrel) Warfarin (vitamin K antagonist) Heparin, including low molecular weight heparin (antithrombin agents) Dabigatran (direct thrombin inhibitor) Apixaban, edoxaban, rivaroxaban (direct factor Xa inhibitors) Note: All above drugs need to be stopped at least 5 half-lives before study drug administration except for aspirin, which needs to be stopped at least 8 days beforehand. Prior/concurrent clinical study experience. The participant is taking part in another interventional clinical trial of another drug substance. Uncooperative behavior or any condition that could make the participant potentially non-adherent with the study procedures The participant is pregnant or is a breastfeeding woman. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAR442168<br>SAR442168 : Experimental - Part A: Double-blind period of continued treatment with the respective SAR442168 dose administered in the DRI15928 study until selection of Phase 3 dose. Part B: Open-label period of a single-group treatment with SAR442168 selected Phase 3 dose of 60 mg. All participants will be switched to this 60 mg dose. | Drug: Tolebrutinib<br>* Pharmaceutical form: Film coated tablet Route of administration: Oral<br>* Other names: SAR442168;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline to final follow-up visit ( Month 60 plus 8 weeks) | 
| Number of Participants with Potentially Clinically Significant Abnormalities | Potentially clinically significant abnormalities (PCSAs) determined by laboratory tests, electrocardiogram (ECG), or vital signs during the study period. | Baseline to final follow-up visit ( Month 60 plus 8 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of new gadolinium (Gd)-enhancing T1 hyperintense lesions | New gadolinium (Gd)-enhancing T1 hyperintense lesions determined by brain Magnetic Resonance Imaging (MRI) | Baseline to final follow-up visit ( Month 60 plus 8 weeks) | 
| Number of new or enlarging T2 lesions | T2 lesions, a marker of inflammatory activity and brain tissue destruction in RMS will be evaluated by MRI | Baseline to final follow-up visit ( Month 60 plus 8 weeks) | 
| Total number of Gd-enhancing T1-hyperintense lesions | Total number of Gd-enhancing T1-hyperintense lesions | Baseline to final follow-up visit ( Month 60 plus 8 weeks) | 
| Number of participants wih relapse (Annualized Relapse rate) | Annualized Relapse rate is defined as the number of participants with relapse during the study period. | Baseline to Month 60 | 
| Change in Expanded Disability Status Scale (EDSS) from baseline over time | Standard EDSS assessments of neurological symptoms in each of 7 functional domains (visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral and bowel/bladder) will be performed. Ambulation will also be scored as part of the evaluation. | Baseline to final follow-up visit ( Month 60 plus 8 weeks) |