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

• ClinicalTrials.gov Identifier: NCT06141473
• Recruitment Status: Recruiting
• First Posted: November 21, 2023
• Last Update Posted: May 16, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: November 9, 2023
• First Posted Date: November 21, 2023
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: December 13, 2023
• Estimated Primary Completion Date: May 6, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2023)

Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses [ Time Frame: 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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 2, 2024)

• Time to onset of composite confirmed disability worsening (cCDW) [ Time Frame: 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 [ Time Frame: Until Week 156 ]
• Time to onset of individual components of the composite, confirmed over 3-months or 6-months [ Time Frame: Until Week 156 ]
• Time to onset of confirmed disability improvement (CDI) [ Time Frame: 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 [ Time Frame: 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
• 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 [ Time Frame: Until Week 156 ]
• Total number of new Gd-enhancing T1hyperintense lesions per scan as detected by MRI [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: From baseline to Week 156 ]
• Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time [ Time Frame: From baseline to Week 156 ]
• Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time [ Time Frame: 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 [ Time Frame: Until Week 168 ]
• Number of participants with potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG and vital signs during the study period [ Time Frame: 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 [ Time Frame: Until Week 156 ]
• Change from baseline in plasma neurofilament light chain (NfL) levels over time [ Time Frame: Until Week 144 ]
• Frexalimab plasma concentration over time [ Time Frame: Until Week 144 ]

Original Secondary Outcome Measures (submitted: November 15, 2023)

• Time to onset of composite confirmed disability worsening (cCDW) [ Time Frame: 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 ≤5.5, 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
• Time to onset of cCDW, confirmed over 3 months [ Time Frame: Until Week 156 ]
• Time to onset of individual components of the composite, confirmed over 3-months or 6-months [ Time Frame: Until Week 156 ]
• Time to onset of confirmed disability improvement (CDI) [ Time Frame: Until Week 156 ]
  defined as 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 pointsa
• Progression independent of relapse activity defined as the time to onset of 6-month cCDW [ Time Frame: 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
• 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 [ Time Frame: Until Week 156 ]
• Total number of new Gd-enhancing T1hyperintense lesions per scan as detected by MRI [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: From baseline to Week 156 ]
• Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time [ Time Frame: From baseline to Week 156 ]
• Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time [ Time Frame: 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 [ Time Frame: Until Week 168 ]
• Number of participants with potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG and vital signs during the study period [ Time Frame: 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 [ Time Frame: Until Week 156 ]
• Change from baseline in plasma neurofilament light chain (NfL) levels over time [ Time Frame: Until Week 144 ]
• Frexalimab plasma concentration over time [ Time Frame: Until Week 144 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-dummy

Primary Purpose: Treatment

• Condition: Multiple Sclerosis

Intervention

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

Study Arms

• Experimental: Frexalimab
  Participants will receive Frexalimab infusion and placebo tablet.
  Interventions:

  • Drug: Frexalimab
  • Drug: Placebo tablet
  • Drug: MRI contrast-enhancing agents
  • Drug: Cholestyramine
  • Drug: Activated charcoal
• Active Comparator: Teriflunomide
  Participants will receive teriflunomide tablet and placebo infusion.
  Interventions:

  • Drug: Teriflunomide
  • Drug: Placebo infusion
  • Drug: MRI contrast-enhancing agents
  • Drug: Cholestyramine
  • Drug: Activated charcoal

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 15, 2023): 1400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 6, 2027
• Estimated Primary Completion Date: May 6, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; contact-us@sanofi.com

• Listed Location Countries: Canada, Chile, Israel, Puerto Rico, United Kingdom, United States

Administrative Information

• NCT Number: NCT06141473
• Other Study ID Numbers: EFC17919; 2023-504358-36 ( Registry Identifier: CTIS ); U1111-1290-9326 ( Registry Identifier: ICTRP )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Sanofi
• Verification Date: May 2024