Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis

NCT06141473
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
1,655
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Lead sponsor
Sanofi
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Start date
2023-12-13
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Number of sites
382
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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 scheduled visits will include monthly visits for the first 6 months and quarterly visits thereafter until the common end of study (EOS), or premature end of treatment (pEOT) after which 3 follow-up visits will be performed
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Acronym
FREXALT
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Short title
Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis
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Official title
Master Protocol of Two Independent, Randomized, Double-blind, Phase 3 Studies Comparing Efficacy and Safety of Frexalimab (SAR441344) to Teriflunomide in Adult Participants With Relapsing Forms of Multiple Sclerosis
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2027-05-06
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First posted
2023-11-21
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Registry last updated
2026-07-20
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Primary completion date
2027-05-06
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Start date
2023-12-13
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Actual participants
1,655
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Participants
1,655
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Participant count basis
Actual
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Protocol amendments
5
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Number of sites
382
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Sanofi
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06141473
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ClinicalTrials.gov ID
NCT06141473
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masking description
Double-dummy
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses

    Timeframe: 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).

  1. Time to onset of composite confirmed disability worsening (cCDW)

    Timeframe: 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

  2. Time to onset of cCDW, confirmed over 3 months

    Timeframe: Until Week 156

  3. Time to onset of individual components of the composite, confirmed over 3-months or 6-months

    Timeframe: Until Week 156

  4. Time to onset of confirmed disability improvement (CDI)

    Timeframe: 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

  5. Progression independent of relapse activity defined as the time to onset of 6-month cCDW

    Timeframe: Until Week 156

    defined by either no prior relapse or an onset more than 90 days after the start date of the last adjudicated relapse

  6. Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI

    Timeframe: 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

  7. Total number of new Gd-enhancing T1hyperintense lesions per scan as detected by MRI

    Timeframe: 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

  8. Percent change in brain volume loss as detected by brain MRI scans at the EOS compared to Month 6

    Timeframe: From Week 24 to Week 156

  9. Change in cognitive function at the EOS compared to baseline as assessed by the symbol digit modalities test (SDMT)

    Timeframe: From baseline to Week 156

  10. Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time

    Timeframe: From baseline to Week 156

  11. Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time

    Timeframe: Until Week 156

  12. Number of participants with adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs and safety scales during the study period

    Timeframe: Until Week 168

  13. Number of participants with potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG and vital signs during the study period

    Timeframe: 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.

  14. Number of participants with antidrug (ADAs) over time

    Timeframe: Until Week 156

  15. Change from baseline in plasma neurofilament light chain (NfL) levels over time

    Timeframe: Until Week 144

  16. Frexalimab plasma concentration over time

    Timeframe: Until Week 144

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults
Minimum age
18 Years
Maximum age
55 Years
Healthy volunteers
No

  • 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.

  • 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.

Sources for eligibility
clinicaltrials.gov

  • University of Alabama at Birmingham- Site Number : 8401135Birmingham, United States
  • North Central Neurology Associates- Site Number : 8401100Cullman, United States
  • Alabama Neurology Associates- Site Number : 8400115Homewood, United States
  • St. Joseph's Hospital and Medical Center- Site Number : 8401139Phoenix, United States
  • Perseverance Research Center- Site Number : 8401138Scottsdale, United States
  • Clinical Endpoints- Site Number : 8400050Scottsdale, United States
  • The Neurology Center of Southern California - Carlsbad- Site Number : 8400023Carlsbad, United States
  • University of California Irvine - School of Medicine- Site Number : 8401143Irvine, United States
  • Multiple Sclerosis Center of California - Laguna Hills- Site Number : 8401122Laguna Hills, United States
  • Chemidox Clinical Trials- Site Number : 8401157Lancaster, United States
  • Hoag Memorial Hospital Presbyterian- Site Number : 8401031Newport Beach, United States
  • West Hollywood, United States
  • University of Colorado - Anschutz Medical Campus- Site Number : 8401001Aurora, United States
  • Advanced Neurology of Colorado- Site Number : 8401148Fort Collins, United States
  • Hartford Healthcare Medical Group- Site Number : 8401069Norwich, United States
  • New England Institute for Clinical Research- Site Number : 8400114Stamford, United States
  • MedStar Georgetown University Hospital- Site Number : 8400044Washington D.C., United States
  • Neurology of Central Florida- Site Number : 8401147Altamonte Springs, United States
  • Neurology Offices of South Florida - Boca Raton- Site Number : 8401169Boca Raton, United States
  • First Choice Neurology - Espinosa Neuroscience Institute- Site Number : 8401071Boca Raton, United States
  • Nova Clinical Research - Bradenton- Site Number : 8400189Bradenton, United States
  • Mayo Clinic in Florida- Site Number : 8401093Jacksonville, United States
  • Neurology Associates - Maitland- Site Number : 8400010Maitland, United States
  • University of Miami Hospital- Site Number : 8401177Miami, United States
  • Design Neuroscience Center- Site Number : 8401191Miami Lakes, United States

And 357 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-504358-36
  • U1111-1290-9326
Sources for references
clinicaltrials.gov

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