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

Sanofi

Status and phase: Completed; Phase 3

Conditions: Secondary Progressive Multiple Sclerosis

Treatments: Drug: Placebo to match Tolebrutinib; Drug: Tolebrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04411641

2020-000647-30 (EudraCT Number)

EFC16645

U1111-1246-7768 (Other Identifier)

Details and patient eligibility

About

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

Full 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.

Enrollment: 1,131 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.
• History of organ transplant.
• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,131 participants in 2 patient groups, including a placebo group

SAR442168

Experimental group

Description:

Dose 1 of oral SAR442168 once daily

Treatment:

Drug: Tolebrutinib

Placebo

Placebo Comparator group

Description:

Placebo tablet to match SAR442168 once daily

Treatment:

Drug: Placebo to match Tolebrutinib