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

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06141473
• Other study ID #: EFC17919
• Secondary ID: 2023-504358-36U1
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2023
• Est. completion date: May 6, 2027

Study information

• Verified date: May 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free number for US &
• Phone: 800-633-1610
• Email: contact-us[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 of approximately 40 months for the first participant being randomized and approximately 20 months for the last participant randomized. - The study intervention duration will vary ranging from approximately 20 to 40 months. - 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1400
• Est. completion date: May 6, 2027
• Est. primary completion date: May 6, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.
• History or current 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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Frexalimab
SAR441344 Solution for IV infusion
• Teriflunomide
Aubagio oral tablet
• Placebo infusion
Solution for IV infusion
• Placebo tablet
Oral tablet
• MRI contrast-enhancing agents
IV, as per respective label
• Cholestyramine
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.
• Activated charcoal
oral, 50 g every 12 hours for 11 days for accelerated elimination procedure. The teriflunomide local label should be followed.

Locations

Country	Name	City	State
Canada	Investigational Site Number : 1240001	Gatineau	Quebec
Canada	Investigational Site Number : 1240004	Granby	Quebec
Canada	Investigational Site Number : 1240008	Levis	Quebec
Chile	Investigational Site Number : 1520004	Santiago de Chile
Israel	Investigational Site Number : 3760001	Haifa
Puerto Rico	San Juan MS Center Site Number : 8401106	Guaynabo
United Kingdom	Investigational Site Number : 8261003	Canterbury	Kent
United States	Abington Neurological Associates Site Number : 8401065	Abington	Pennsylvania
United States	University of New Mexico Site Number : 8401090	Albuquerque	New Mexico
United States	Neurology of Central Florida Research Center, LLC Site Number : 8401147	Altamonte Springs	Florida
United States	Alabama Neurology Associates Site Number : 8400115	Birmingham	Alabama
United States	The Research Center of Southern California, LLC Site Number : 8400023	Carlsbad	California
United States	Dayton Center for Neurological Disorders Site Number : 8400079	Centerville	Ohio
United States	Piedmont Healthcare/Research Site Number : 8400002	Charlotte	North Carolina
United States	The Boster Center for Multiple Sclerosis Site Number : 8400006	Columbus	Ohio
United States	NorthShore University Healthsystem Site Number : 8401111	Evanston	Illinois
United States	Michigan Institute For Neurological Disorders Site Number : 8400004	Farmington Hills	Michigan
United States	HOPE Neurology Site Number : 8400019	Knoxville	Tennessee
United States	International Neurorehabilitation Institute Site Number : 8400089	Lutherville	Maryland
United States	Neurology Associates, PA Site Number : 8400010	Maitland	Florida
United States	Neuroscience Institute Center Site Number : 8400053	Merrillville	Indiana
United States	Consultants In Neurology Site Number : 8401020	Northbrook	Illinois
United States	Oklahoma Medical Research Foundation Site Number : 8400039	Oklahoma City	Oklahoma
United States	College Park Family Care Center Site Number : 8400032	Overland Park	Kansas
United States	Memorial Healthcare Institute for Neuroscience Site Number : 8400123	Owosso	Michigan
United States	Sharlin Health & Neurology Site Number : 8400016	Ozark	Missouri
United States	North Texas Institute of Neurology - Plano Site Number : 8401083	Plano	Texas
United States	Velocity Clinical Research, Inc Site Number : 8400014	Raleigh	North Carolina
United States	Neurology Center of San Antonio Site Number : 8400099	San Antonio	Texas
United States	Perseverance Research Center, LLC Site Number : 8401138	Scottsdale	Arizona
United States	Texas Institute for Neuroogical Disorders-Sherman Site Number : 8400018	Sherman	Texas
United States	Axiom Clinical Research of Florida Site Number : 8400049	Tampa	Florida
United States	Regina Berkovich, MD, PhD Site Number : 8400005	West Hollywood	California
United States	Premiere Research Institute at Palm Beach Neurology Site Number : 8401105	West Palm Beach	Florida
United States	Atrium Health Wake Forest Baptist Site Number : 8400040	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Canada,  Chile,  Israel,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses	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).	Until Week 156
Secondary	Time to onset of composite confirmed disability worsening (cCDW)	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	Until Week 156
Secondary	Time to onset of cCDW, confirmed over 3 months		Until Week 156
Secondary	Time to onset of individual components of the composite, confirmed over 3-months or 6-months		Until Week 156
Secondary	Time to onset of confirmed disability improvement (CDI)	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	Until Week 156
Secondary	Progression independent of relapse activity defined as the time to onset of 6-month cCDW	defined by either no prior relapse or an onset more than 90 days after the start date of the last investigatorreported relapse	Until Week 156
Secondary	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 month		Until Week 156
Secondary	Total number of new Gd-enhancing T1hyperintense lesions per scan as detected by MRI	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	Until Week 156
Secondary	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
Secondary	Change in cognitive function at the EOS compared to baseline as assessed by the symbol digit modalities test (SDMT)		From baseline to Week 156
Secondary	Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time		From baseline to Week 156
Secondary	Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time		Until Week 156
Secondary	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
Secondary	Number of participants with potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG and vital signs during the study period	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.	Until Week 168
Secondary	Number of participants with antidrug (ADAs) over time		Until Week 156
Secondary	Change from baseline in plasma neurofilament light chain (NfL) levels over time		Until Week 144
Secondary	Frexalimab plasma concentration over time		Until Week 144