Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS) Study of Bruton's Tyrosine Kinase (BTK) Inhibitor Tolebrutinib (SAR442168) (HERCULES)

Prior treatment

• History of alcohol or drug abuse within 1 year prior to screening.
• Hospitalized for psychiatric disease within 2 years prior to screening.
• 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 or gastrointestinal bleeding.
• Recent live (attenuated) vaccine within 2 months before the first treatment visit.
• Recent major surgery (within 4 weeks of screening) or planned major surgery during the study.
• The participant has received medications/treatments for MS within a specified time frame.
• Receiving potent and moderate inducers or inhibitors of cytochrome P450 3A (CYP3A) or potent inhibitors of CYP2C8 hepatic enzymes.
• Receiving anticoagulant or antiplatelet therapy (such as aspirin\>81mg/day, clopidogrel, warfarin).

Other illness

• The participant has conditions that would adversely affect study participation such as short life expectancy.
• Evidence of infection with human immuodeficiency virus (HIV), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infections that would adversely affect study participation.
• Persistent chronic or active or recurring system infection, that may adversely affect participation or IMP administration in this study, as judged by the Investigator.
• History of malignancy within 5 years prior to screening.

Lab values

• Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at screening
• Bleeding disorder, known platelet dysfunctionat any time prior to the screening visit
• A platelet count \<150 000/μL at the screening visit
• Lymphocyte count below the lower limit of normal at screening.

Other

• Contraindications to magnetic resonance imaging (MRI).
  • The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• 18 to 60 years of age inclusive
• Diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the 2017 McDonald criteria
• Expanded disability status scale (EDSS) between 3.0 to 6.5 points inclusive, at screening
• The participant must have documented evidence of disability progression observed during the 12 months before screening
• Absence of clinical relapses for at least 24 months
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
• Is not a WOCBP OR
• Is a WOCBP and agrees to use an acceptable contraceptive method