Multiple Sclerosis
Conditions
Brief summary
The purpose of this randomized, double-blind, placebo-controlled, parallel group study is to determine the efficacy of frexalimab in delaying the disability progression and the safety up to 36 months double-blind administration of study intervention compared to placebo in male and female participants with nrSPMS (aged 18 to 60 years at the time of enrollment). People diagnosed with nrSPMS 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 end when the target number of 6-month cCDP events is achieved, and the study is expected to last 43 months from randomization of the first participant to the common study end. * The number of scheduled visits will be up to 25 (including 3 follow-up visits) with a visit frequency of every month for the first 6 months and then every 3 months. * If the prespecified number of events for 6-month cCDP is not reached by V21/W180, scheduled visits will continue every 3 months.
Interventions
DRUGFrexalimab
SAR441344 Solution for IV infusion
DRUGPlacebo
Solution for IV infusion
IV, as per respective label
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Participant must have a previous diagnosis of RRMS in accordance with the 2017 revised McDonald criteria. * Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013 endorsed by an Adjudication Committee. * Participant must have documented evidence of disability progression observed during the 12 months before screening. Eligibility will be analyzed by an Adjudication Committee. * Absence of clinical relapses for at least 24 months. * The participant must have an EDSS score at screening from 3.0 to 6.5 points, inclusive. * Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * For patients eligible to be treated with siponimod: 1) does not tolerate it due to side effects or safety reasons, or 2) has failed siponimod treatment due to perceived lack of efficacy, or 3) has declined siponimod treatment.
Exclusion 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 immunoglobulin levels (IgG and/or IgM) below the lower limits of normal (LLN) at Screening or a history of primary hypogammaglobulinemia. Patients with a history of secondary hypogammaglobulinemia induced by anti-C20 monoclonal antibodies (eg, ocrelizumab, ofatumumab, ublituximab, rituximab) may be considered for study inclusion provided their immunoglobulin levels are within the normal limits (WNL) at time of Screening. * 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 sensitivity to any of the study interventions, or components thereof, or has a drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. * The participant was previously exposed to frexalimab. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to onset of composite confirmed disability progression (cCDP) confirmed over 6 months in the double-blind treatment period | Up to 36 months | Defined as Increase from the baseline expanded disability status scale (EDSS) score of ≥1.0 point when the baseline is \<5.5, 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time in the double-blind treatment period | Baseline, Up to 36 months | — |
| Time to onset of composite cCDP confirmed over 3 months in the double-blind treatment period | Up to 36 months | — |
| Time to onset of individual components of the composite, confirmed over 3-months or 6 months in the double-blind treatment period | Up to 36 months | increase from the baseline EDSS score of ≥1.0 point when the baseline is \<5.5, or ≥0.5 point when the baseline is ≥5.5 |
| Time to onset of confirmed disability improvement (CDI) in the double-blind treatment period | Up to 36 months | defined as decrease from the baseline EDSS score of ≥1.0 or ≥ 0.5 points when baseline is ≤5.5 or \>5.5 points, respectively, confirmed over 6 months. |
| Number of new and/or enlarging T2hyperintense lesions per scan as detected by MRI, and number of new and/or enlarging T2-hyperintense lesions per scan as detected by MRI | Up to 36 months | defined as the sum of the individual number of new and/or enlarging T2-hyperintense lesions at all scheduled visits starting after baseline up to the end of double-blind treatment period |
| Percent change in brain volume loss as detected by MRI scans at the end of double-blind treatment period compared to Month 6 | Up to 36 months | — |
| Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue multiple sclerosis (MS)-8a over time in the double-blind treatment period | Baseline, Up to 36 months | — |
| Annualized relapse rate during the double-blind treatment period assessed by protocol defined adjudicated relapses | Up to 36 months | — |
| Number of participants with adverse events, SAEs, AEs leading to permanent study intervention discontinuation and AE of special interests (AESIs) | Up to 36 months | — |
| Number of participants with potentially clinically significant abnormalities (PCSAs) in laboratory tests, ECG, and vital signs during the study period | Up to 36 months | 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 antibody over time | Up to 36 months | — |
| Change from baseline in serum Ig levels over time | Up to 36 months | — |
| Change from baseline in plasma neurofilament light chain (NfL) levels over time in the double-blind treatment period | Up to 36 months | — |
| Change in cognitive function at the end of double-blind treatment period compared to baseline as assessed by symbol digit modalities test (SDMT) | Baseline, Up to 36 months | — |
| Frexalimab plasma concentration over time in the double-blind treatment period | Up to 36 months | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Greece, Hungary, India, Italy, Japan, Netherlands, Poland, Portugal, Saudi Arabia, South Korea, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
CONTACTTrial Transparency email recommended (Toll free number for US & Canada)
Outcome results
None listed