Primary Progressive Multiple Sclerosis (PPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (PERSEUS)

Inclusion Criteria:

• 18 to 55 years of age inclusive

• Diagnosis of PPMS according to the 2017 McDonald criteria

• Expanded disability status scale (EDSS) score between 2.0 to 6.5 points, atscreening inclusive

• Positive cerebrospinal fluid oligoclonal bands and/or elevated Immunoglobulin G (IgG) index either during screening or documented previous history.

• Contraceptive use consistent with local regulations for individuals participating inclinical studies

• Participant is eligible to participate if she is not pregnant or breastfeeding, andat least one of the following conditions applies:

• Is not a woman of childbearing potential (WOCBP) or is a WOCBP and agrees to use anacceptable contraceptive method

• the participant must not have access to ocrelizumab (eg, ocrelizumab not availableon the national market or not reimbursed for the approved indication).

• the participant must have access to and be eligible to be treated with ocrelizumabbut: 1) does not tolerate it due to side effects or safety reasons; and/or 2) hasfailed ocrelizumab treatment due to perceived lack of efficacy

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Participant has conditions that would adversely affect study participation such asshort life expectancy.

• Evidence of infection with human immunodeficiency virus (HIV), transplantation,progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active orlatent tuberculosis or other active infection that would adversely affect studyparticipation.

• Persistent chronic or active or recurring system infection that may adversely affectparticipation or IMP administration in this study as judged by the investigator

• History of malignancy within 5 years prior to screening.

• History of alcohol or drug abuse within 1 year prior to Screening.

• Hospitalized for psychiatric disease within 2 years prior to Screening.

• Clinically significant laboratory abnormalities (including evidence of liver injury)or electrocardiogram abnormalities at Screening.

• A bleeding disorder or known platelet dysfunction at any time prior to the screeningvisit.

• A platelet count <150 000/μL at the screening visit.

• A history of significant bleeding event within 6 months prior to screening,according to the Investigator's judgment such as, but not limited to cerebral orgastrointestinal

• Lymphocyte count below the lower limit of normal at Screening.

• Recent live (attenuated) vaccine within 2 months before the first treatment visit.

• Recent major surgery (within 4 weeks of Screening) or planned major surgery duringthe study.

• The participant has received medications/treatments for MS within a specified timeframe.

• Receiving potent and moderate inducers of cytochrome P450 3A (CYP3A) or potentinhibitors of CYP2C8 hepatic enzymes.

• Receiving anticoagulant or antiplatelet therapy (such as aspirin >81mg/day,clopidogrel, warfarin).

• Contraindications to magnetic resonance imaging (MRI).

NOTE: Other Inclusion/Exclusion criteria may apply. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial