Multiple Sclerosis
Conditions
Brief summary
The purpose of each study is to independently measure the annualized relapse rate (ARR) with administration of frexalimab compared to a daily oral dose of teriflunomide in male and female participants with relapsing forms of multiple sclerosis (aged 18 to 55 years at the time of enrollment). People diagnosed with relapsing forms of multiple sclerosis are eligible for enrollment as long as they meet all the inclusion criteria and none of the exclusion criteria. Study details include: * This event-driven study will have variable duration depending on the recruitment rate, the event rate, the study discontinuation rate and the 12-month minimum treatment duration. Different participants will have different study durations. The last participant randomized will have at least 12 months of study duration, and assuming a 28-month recruitment period, the first participant randomized will have 40 months or longer of study duration. * The study intervention duration will vary similarly as the study duration. * The assessment of scheduled visits will include 1 common end of study \[EOS\] visit and 3 follow-up visits) with a visit frequency of every 4 weeks for the first 6 months and then every 3 months.
Interventions
DRUGFrexalimab
SAR441344 Solution for IV infusion
DRUGTeriflunomide
Aubagio oral tablet
DRUGPlacebo infusion
Solution for IV infusion
DRUGPlacebo tablet
Oral tablet
IV, as per respective label
DRUGCholestyramine
oral, 8 g 3 times daily for 11 days for accelerated elimination procedure (4 g 3 times daily for 11 days in case of intolerance). The teriflunomide local label should be followed.
oral, 50 g every 12 hours for 11 days for accelerated elimination procedure. The teriflunomide local label should be followed.
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-dummy
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria. * The participant has an EDSS score ≤5.5 at the first visit (Screening Visit) * The participant must have 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 lesion on an MRI scan within the previous year. * Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Exclusion criteria
* The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria * The participant has a history of infection or may be at risk for infection: * The presence of psychiatric disturbance or substance abuse. * History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphosholipid syndrome and any participants requiring antithrombotic treatment. * Current hypogammaglobulinemia defined by Ig levels below the LLN at Screening or a history of primary hypogammaglobulinemia. * A history or presence of disease that can mimic MS symptoms, such as, but not limited to neuromyelitis optica spectrum disorder, systemic lupus erythematosus, Sjogren's syndrome, acute disseminated encephalomyelitis, and myasthenia gravis. * The participant has had a relapse in the 30 days prior to randomization. * The participant has contraindication for MRI, ie, presence of pacemaker, metallic implants in high risk areas (ie, artificial heart valves, aneurysm/vessel clips), presence of metallic material (eg, shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol scheduled MRI scans. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses | Until Week 156 | ARR during the study period assessed by protocol-defined adjudicated relapses. This endpoint will be analyzed in the ITT population of each study using a negative binomial model with the total number of adjudicated relapses per participant occurring during the observation period as the response variable and with terms for treatment group, Gd-enhancing T1 lesions at baseline (presence, absence), EDSS strata (\<4, ≥4), and geographical region (US, non-US). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to onset of composite confirmed disability worsening (cCDW) | Until Week 156 | confirmed over 6 months as assessed by the composite of: * increase from the baseline expanded disability status scale (EDSS) score of ≥1.5 points when the baseline is 0, or ≥1.0 point when the baseline is 0.5 to 5.0, or ≥0.5 point when the baseline is ≥5.5, OR * increase of ≥20% from the baseline time in the 9-hole peg test (9HPT), OR * increase of ≥20% from the baseline time in the Timed 25-foot walk (T25FW) test |
| Time to onset of cCDW, confirmed over 3 months | Until Week 156 | — |
| Time to onset of individual components of the composite, confirmed over 3-months or 6-months | Until Week 156 | — |
| Time to onset of confirmed disability improvement (CDI) | Until Week 156 | defined as decrease from baseline EDSS score of ≥1.0 or ≥ 0.5 points when the baseline is ≥2 to ≤5.5 or \>5.5 points, respectively, confirmed over 6 months. No improvement possible for 0 to 1.5 points |
| Progression independent of relapse activity defined as the time to onset of 6-month cCDW | Until Week 156 | defined by either no prior relapse or an onset more than 90 days after the start date of the last investigatorreported relapse |
| Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI | Until Week 156 | defined as the sum of the individual number of new and/or enlarging T2 lesions at all scheduled visits starting after baseline up to and including the EOS visit |
| Total number of new Gd-enhancing T1hyperintense lesions per scan as detected by MRI | Until Week 156 | defined as the sum of the individual number of new Gd enhancing T1-hyperintense lesions at all scheduled visits starting after baseline up to and including the EOS visit divided by the number of scans |
| Percent change in brain volume loss as detected by brain MRI scans at the EOS compared to Month 6 | From Week 24 to Week 156 | — |
| Change in cognitive function at the EOS compared to baseline as assessed by the symbol digit modalities test (SDMT) | From baseline to Week 156 | — |
| Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time | From baseline to Week 156 | — |
| Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time | Until Week 156 | — |
| Number of participants with adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs and safety scales during the study period | Until Week 168 | — |
| Number of participants with potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG and vital signs during the study period | Until Week 168 | 12-lead ECG (electrocardiogram) will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. |
| Number of participants with antidrug (ADAs) over time | Until Week 156 | — |
| Change from baseline in plasma neurofilament light chain (NfL) levels over time | Until Week 144 | — |
| Frexalimab plasma concentration over time | Until Week 144 | — |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Croatia, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Lithuania, Malaysia, Mexico, Poland, Portugal, Puerto Rico, Romania, Saudi Arabia, Singapore, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Arab Emirates, United Kingdom, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free number for US & Canada)
Outcome results
None listed