Summary:
Brief Summary:
Primary Objective:
To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS
Secondary Objective:
To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance imaging (MRI) lesions, cognitive performance, physical function, and quality of life To evaluate safety and tolerability of SAR442168 To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites in NRSPMS and its relationship to efficacy and safety To evaluate pharmacodynamics (PD) of SAR442168
Detailed Description:
Study duration will vary per participant in this event driven trial with a treatment duration of approximately 24 to 48 months. Participants completing the treatment period will be proposed to enroll in a separate Long term safety study.
Inclusion criteria :
- 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
The participant must have, at screening, disease duration from the onset of MS symptoms of:
- <20 years in participants with EDSS scores at screening >5.0; OR
- <10 years in participants with EDSS scores at screening ≤5.0
- 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
Exclusion criteria:
- The participant has conditions that would adversely affect study participation such as short life expectancy.
- History of organ transplant.
- Evidence of infection with human immuodeficiency virus (HIV), progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infections that would adversely affect study participation.
- 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
- Bleeding disorder, known platelet dysfunction or platelet count <150 000/μL at 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.
- 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 during the study.
- The participant has received medications/treatments for MS within a specified time frame.
- Receiving strong inducers or inhibitors of cytochrome P450 3A (CYP3A) or CYP2C8 hepatic enzymes.
- Receiving anticoagulant or antiplatelet therapy (such as aspirin, clopidogrel, warfarin).
- Contraindications to magnetic resonance imaging (MRI).
Qualified Participants May Receive:
Study-related care and treatments at no cost, compensation for time and travel.