demyelinating disease Multiple sclerosis
Conditions
Interventions
Participants will be randomly assigned at a 1:1 ratio to receive the 60 mg 
selected dose
(established from dose-finding Study DRI15928) of oral SAR442168 daily as well 
as a placebo to
match the teriflunomide tablet, or 14 mg oral teriflunomide as well as a 
placebo to match the
SAR442168 tablet daily. Randomization will be stratified by EDSS score at 
screening (<
4 versus >
=4) and geographic region (US versus non-US).
Sponsors
Sanofi B.V.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: *18 to 55 year old male or female with RMS *EDSS score of <= 5.5 points at screening *At least 1 of the following prior to screening: - >=1 documented relapse within the previous year OR - >=2 documented relapses within the previous 2 years, OR - >=1 documented Gd-enhancing brain lesion on an MRI scan within the previous year. *Without: -PPMS diagnosis -Significant infection/at increased infection risk -Significant psychiatric disease or substance abuse -Excess bleeding risk or use of antiplatelets/anticoagulants -Recent use of MS treatments -Significant other concomitant illness/short life expectancy *If female of childbearing potential: --not pregnant or breastfeeding, and agrees to use acceptable contraceptive method during the intervention period (at a minimum until after the last IMP dose) Note. The initial clinical demyelinating episode of MS should be counted as a relapse for the first 2 criteria.
Exclusion criteria
Exclusion criteria: -Diagnose of PPMS -History of infection or at risk for infection -Presence of psychiatric disturbance or substance abuse -Confirmed laboratory or ECG abnormalities, during the screening visit, deemed by the investigator to be clinically significant. -Conditions that may predispose the participant to excessive bleeding -Conditions that would adversely affect participation in study or make primary efficacy endpoint non-evaluable -Receiving strong inducers or inhibitors of cytochrome P450 3A (CYP3A) or CYP2C8 hepatic enzymes -Receiving anticoagulant/antiplatelet therapies -Sensitivity to study interventions, or drug or other allergy that, per Investigator, contraindicates participation in the study. -Previously exposed to any BTK inhibitor, including SAR442168. -Taken other investigational drugs within 3 months or 5 half-lives, whichever is longer, before SCR. -A relapse in the 30 days prior to randomization -Contraindication for MRI (People with contraindication to gadolinium (Gd) can be enrolled but cannot receive Gd during MRI scan.) -Institutionalized because of regulatory or legal order; prisoners or participants who are legally institutionalized. -Any country-related regulation that would prevent entering the study, if applicable. -Not suitable for participation, whatever the reason, as judged by Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures or not able to follow protocol assessments -Dependent on Sponsor or Investigator -Employees of study site or directly involved in conduct of study, or immediate family members of such individuals. -Any other situation during study course that may raise ethics considerations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint is the time to onset of CDP (confirmed for at least 6 months) assessed by the annualized adjudicated relapse rate(AARR). | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints from time to event will be analysed in a similar manner to the primary efficacy endpoint. • Time to start of composite CDP • Time to start of 3 months CDP • Time to CDI • Total number of new and / or growing hyperintense T2 lesions using MRI • Percentage change in brain volume loss using MRI • Change in cognitive function using the SDMT • Change in the score on the *quality of life* questionnaire • Adverse reactions (Aes), serious adverse events (SAEs), safety results on MRI, and possible clinically significant abnormalities in laboratory results, on electrocardiogram (ECG) or in vital signs during the study period. | — |
Countries
Netherlands
Outcome results
None listed