Primary Progressive Multiple Sclerosis
Conditions
Interventions
Drug: SAR442168 (Tolebrutininb)
Pharmaceutical form: Film-coated Tablet, Route of administration: Oral, Dose 1 of oral SAR442168 daily
Drug: Placebo
Pharmaceutical form: Film-coated Tablet, Route of
Sponsors
Tanaka Tomoyuki
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18 to 55 years of age inclusive - 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 - The participant must not have access to ocrelizumab (eg, ocrelizumab not available on the national market or not reimbursed for the approved indication) - The participant must have access to and be eligible to be treated with ocrelizumab but: 1) does not tolerate it due to side effects or safety reasons; and/or 2) has failed ocrelizumab treatment due to perceived lack of efficacy
Exclusion criteria
Exclusion criteria: - Participant has conditions that would adversely affect study participation such as short life expectancy. - 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 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. - A bleeding disorder or known platelet dysfunction at any time prior to the screening visit. - A platelet count 81mg/day, clopidogrel, warfarin). - Contraindications to magnetic resonance imaging (MRI). NOTE: Other Inclusion/Exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. 3 month composite Confirmed Disability Progression (cCDP) [ Time Frame: Up to approximately 60 months ] Time to onset of 3 month cCDP defined as follows: Increase over at least 3 months of >=1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is =0.5 points when the baseline EDSS score is >5.5, or >=20% from the baseline T25-FW, or >=20% from the baseline 9-HPT | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. 6-month Confirmed Disability Progression (CDP) [ Time Frame: Up to approximately 60 months ] Time to onset of 6-month CDP as assessed by EDSS score 2. 6-month composite Confirmed Disability Progression (cCDP) [ Time Frame: Up to approximately 60 months ] Time to onset of 6-month cCDP 3. Change in T2 hyperintense lesions by MRI [ Time Frame: From screening MRI to approximately 60 months ] Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI after baseline up to and including the end of study (EOS) 4. Time to onset of confirmed disability improvement (CDI) [ Time Frame: Up to approximately 60 months ] Time to onset of CDI defined as >=1.0-point decrease on the EDSS score from baseline confirmed over at least 6 months 5. Percent change in Brain volume (BV) [ Time Frame: From 6 months up to approximately 60 months ] Percent change in brain volume (BV) as detected by brain MRI at the EOS compared to month 6 6. Change in cognitive function as assessed by SDMT [ Time Frame: From Baseline up to approximately 60 months ] Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT) 7. Change in cognitive function as assessed by the CVLT-II [ Time Frame: From Baseline up to approximately 60 months ] Change in cognitive function at the EOS compared to baseline as assessed by the California Verbal Learning Test II(CVLT-II) where available 8. Change in Multiple Sclerosis Quality of Life [ Time Frame: From Baseline up to approximately 60 months ] Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) at the EOS compared to baseline 9. Safety and Tolerability [ Time Frame: From screening up to approximately 60 months ] Number of participants with adverse events (AEs), Serious AEs, AEs leading to permanent study intervention discontinuation, and adverse events of special interest (AESI) 10. Population pharmacokinetics [ Time Frame: Months 6, 9 and 12 ] Plasma concentration of SAR442168 (populati | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Denmark, Estonia, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Latvia, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, South Africa, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed