Resumen

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

Descripción detallada

This was an event-driven (6-month CDP) trial with a variable treatment duration (end-of-study \[EOS\] duration: up to approximately 47months). Participants with 6-month confirmed disability progression (CDP) had an option to receive tolebrutinib in the open-label (OL).

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 60 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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.
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 dysfunctionat any time prior to the screening visit
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 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 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).
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.

Ubicaciones

Investigational Site Number :0320002

Capital Federal, Buenos Aires, Argentina

Investigational Site Number :0320001

CABA, Buenos Aires F.D., Argentina

Investigational Site Number :0320007

Buenos Aires, Argentina

Investigational Site Number :0320006

Córdoba, Argentina

Investigational Site Number :0320005

San Miguel de Tucumán, Argentina

A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing SAR442168 to Placebo in Participants With Nonrelapsing Secondary Progressive Multiple Sclerosis