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

Sanofi1,131 enrolled

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

1,131

Conditions

Non-relapsing Secondary Progressive Multiple Sclerosis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

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 * 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. * 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.

Locations (306)

University of Alabama MS Center-Site Number:8400013

Birmingham, Alabama, United States

Center for Neurology and Spine-Site Number:8400089

Phoenix, Arizona, United States

Arcadia Neurology Center-Site Number:8400070

Arcadia, California, United States

UC San Diego ACTRI-Site Number:8400101

La Jolla, California, United States

Collaborative Neuroscience Research-Site Number:8400045

Long Beach, California, United States

Outcomes

Primary Outcomes

Time to Onset of 6-Month Confirmed Disability Progression (CDP) as Assessed by Expanded Disability Status Scale (EDSS)

The EDSS is a disability scale that assesses the following 7 functional domains: visual, brainstem, pyramidal \[motor\], cerebellar \[coordination\], sensory, cerebral, and bowel/bladder. The total EDSS ranges from 0 (normal) to 10 (death due to multiple sclerosis \[MS\]) (0.5 increments from 1-10; next increase after 0 is 1). Higher scores indicated increased disability. Time to onset of 6-month CDP was defined as the time from randomization to the onset of a sustained increase from baseline in EDSS score of \>=1.0 point from the baseline EDSS score when the baseline score was \<=5.0 or of \>=0.5 points when the baseline EDSS score was \>5.0 confirmed after a minimum 6-month interval.