Primary progressive multiple sclerosis (PPMS) Study of Bruton's tyrosine kinase (BTK) inhibitor tolebrutinib SAR442168 (PERSEUS)
- Conditions
- Primary Progressive Multiple SclerosisMedDRA version: 21.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2020-000645-14-CZ
- Lead Sponsor
- Genzyme Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1320
- 18 to 55 years of age inklusive
- Diagnosis of PPMS according to the 2017 McDonald criteria
- Expanded disability status scale (EDSS) score between 2.0 to 6.5 points, at screening inclusive
- Positive cerebrospinal fluid oligoclonal bands and/or elevated Immunoglobulin G (IgG) index either during screening or documented previous history.
- Contraceptive use consistent with local regulations for individuals participating in clinical studies
Participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the
following conditions applies:
- Is not a woman of child bearing potential (WOCBP)
OR
- Is a WOCBP and agrees to use an acceptable contraceptive method
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1320
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- Participant has conditions that would adversely affect study participation such as short life expectancy.
- History of organ transplant.
- Evidence of infection with human immunodeficiency virus (HIV), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infection 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 alchohol 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.
- A bleeding disorder or known platelet dysfunction at 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.
- 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 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).
NOTE: Other Inclusion/Exclusion criteria may apply
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in Primary Progressive Multiple Sclerosis (PPMS);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<br>To evaluate safety and tolerability of SAR442168<br>To evaluate population pharmacokinetics (PK) of SAR442168 in PPMS and its relationship to efficacy and safety<br>To evaluate pharmacodynamics of SAR442168 <br>;Primary end point(s): 6 month Confirmed Disability Progression (CDP) ; Time to onset of 6 month CDP defined as follows:<br>Increase of =1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is =5.5, or Increase of =0.5 points when the baseline EDSS score is >5.5<br>;Timepoint(s) of evaluation of this end point: Up to approximately 48 months
- Secondary Outcome Measures
Name Time Method