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

Study on the Effectiveness of an Investigational Medication for a Type of Multiple Sclerosis

Not Recruiting
18 years - 60 years
All
Phase 3
1131 participants needed

Study 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

Study Details

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).

Eligibility Criteria

You may be eligible for this study if you meet the following criteria:

  • Conditions: Non-relapsing Secondary Progressive Multiple Sclerosis
  • Age: 18 years - 60 years
  • Gender: All

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.

This study investigates the effectiveness of an investigational medication in individuals with Nonrelapsing Secondary Progressive Multiple Sclerosis (NRSPMS). The purpose of the study is to compare the investigational medication to a placebo to see if it can delay the progression of disability in people with NRSPMS.

Participants will be randomly assigned to receive either the investigational medication or a placebo. The study will involve assessments of clinical endpoints, MRI scans, cognitive performance, physical function, and quality of life to evaluate the medication's effectiveness and safety.

  • Who can participate: Adults aged 18 to 60 with a diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the 2017 McDonald criteria are eligible. Participants must have an Expanded Disability Status Scale (EDSS) score between 3.0 and 6.5 and documented disability progression in the past year.
  • Study details: Participants will be required to take either the investigational medication or a placebo. They will undergo regular assessments, including MRI scans and tests of cognitive and physical function, to monitor the effects of the treatment.
  • Study timelines: The study will last up to approximately 47 months.
Updated on 10 Jul 2025. Study ID: NCT04411641