Proof-of-concept Study for SAR441344 (Frexalimab) in Relapsing Multiple Sclerosis

A Phase 2, Double-blind, Randomized, Placebo-controlled Study Assessing Efficacy and Safety of SAR441344, a CD40L-antagonist Monoclonal Antibody, in Participants With Relapsing Multiple Sclerosis

Primary Objective:

To determine the efficacy of SAR441344 as measured by reduction of the number of new active brain lesions

Secondary Objective:

• To evaluate efficacy of SAR441344 on disease activity as assessed by other MRI measures
• To evaluate the safety and tolerability of SAR441344
• To evaluate pharmacokinetics of SAR441344

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: SAR441344 IV; Drug: placebo IV; Drug: SAR441344 SC; Drug: placebo SC; Drug: MRI contrast-enhancing preparations

Detailed Description

The duration of each participant will be no longer than 320weeks in both parts of the study, including 4 weeks of screening, at maximum 292 weeks of treatment and 24 weeks of follow-up.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5809
    • Investigational Site Number : 1000002
  • Sofia, Bulgaria, 1407
    • Investigational Site Number : 1000001
  • Sofia, Bulgaria, 1113
    • Investigational Site Number : 1000003
• Canada
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 1W2
      • Investigational Site Number : 1240001
• Czechia
  • Brno, Czechia, 65691
    • Investigational Site Number : 2030003
  • Hradec Králové, Czechia, 50005
    • Investigational Site Number : 2030002
  • Jihlava, Czechia, 58633
    • Investigational Site Number : 2030001
  • Ostrava - Poruba, Czechia, 70852
    • Investigational Site Number : 2030005
  • Teplice, Czechia, 415 29
    • Investigational Site Number : 2030004
• France
  • Calais, France, 62107
    • Investigational Site Number : 2500006
• Germany
  • Leipzig, Germany, 04103
    • Investigational Site Number : 2760012
  • Münster, Germany, 48149
    • Investigational Site Number : 2760004
• Russia
  • Kazan', Russia, 420032
    • Investigational Site Number : 6430002
  • Moscow, Russia, 117556
    • Investigational Site Number : 6430007
  • Moscow, Russia, 117997
    • Investigational Site Number : 6430006
  • Moscow, Russia, 127015
    • Investigational Site Number : 6430001
  • Saint Petersburg, Russia, 194044
    • Investigational Site Number : 6430003
  • Saint Petersburg, Russia, 197022
    • Investigational Site Number : 6430005
  • Saint Petersburg, Russia, 197110
    • Investigational Site Number : 6430004
  • Tyumen, Russia, 625000
    • Investigational Site Number : 6430008
• Spain
  • Vigo, Spain, 36312
    • Investigational Site Number : 7240002
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240004
• Turkey (Türkiye)
  • Eskişehir, Turkey (Türkiye), 26040
    • Investigational Site Number : 7920004
  • Istanbul, Turkey (Türkiye), 34265
    • Investigational Site Number : 7920003
  • Mersin, Turkey (Türkiye), 33070
    • Investigational Site Number : 7920002
  • İzmit, Turkey (Türkiye), 41380
    • Investigational Site Number : 7920001
• Ukraine
  • Dnipro, Ukraine, 49005
    • Investigational Site Number : 8040010
  • Dnipro, Ukraine, 49089
    • Investigational Site Number : 8040006
  • Ivano-Frankivsk, Ukraine, 76493
    • Investigational Site Number : 8040008
  • Kyiv, Ukraine, 01135
    • Investigational Site Number : 8040002
  • Lviv, Ukraine, 79013
    • Investigational Site Number : 8040004
  • Odesa, Ukraine, 65025
    • Investigational Site Number : 8040003
  • Vinnytsia, Ukraine, 21001
    • Investigational Site Number : 8040005
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Center for Neurology and Spine- Site Number : 8400007
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida Site Number : 8400001
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • The Neurological Institute Site Number : 8400004
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin- Site Number : 8400006

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• The participant must have been diagnosed with RMS (relapsing-remitting MS and secondary progressive MS participants with relapses) according to the 2017 revision of the McDonald diagnostic criteria.
• The participant must have at least 1 documented relapse within the previous year, or ≥2 documented relapses within the previous 2 years, or ≥1 active Gd-enhancing brain lesion on an MRI scan in the past 6 months and prior to screening.
• Body weight within 45 to 120 kg (inclusive) and body mass index (BMI) within the range 18.0 to 35.0 kg/m2 (inclusive) at Screening.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Capable of giving signed informed consent.

Exclusion criteria:

• The participant was diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria or with non-relapsing SPMS.
• The participant had conditions or situations that would adversely affect participation in this study.
• The participant had a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study.
• 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.
• Allergies to humanized monoclonal antibodies or severe post-treatment hypersensitivity reactions other than localized injection site reaction, to any biological molecule.
• The participant had received any of the forbidden medications/treatments within the specified time frame before any baseline assessment.
• The participant had taken other investigational drug within 3 months or 5-half-live, whichever is longer, before the screening visit.
• The participant had an EDSS score >5.5 at the first screening visit.
• The participant had a relapse in the 30 days prior to randomization.
• Positive human immunodeficiency virus (HIV) serology (anti HIV1 and anti HIV2 antibodies) or a known history of HIV infection, active or in remission.
• Abnormal laboratory test(s) at Screening.
• Presence of Hepatitis B surface antigen (HBsAg) or anti-Hepatitis B core antibodies (anti-HBc Ab) at screening or within 3 months prior to first dose of study intervention.
• Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: IV Placebo; Placebo IV	Drug: placebo IV; Pharmaceutical form: Solution Route of administration: IV infusion; Drug: MRI contrast-enhancing preparations; gadolinium compound, including but not limited to Magnevist, Multihance, Prohance, or Elucirem
Placebo Comparator: SC Placebo; Placebo SC	Drug: placebo SC; Pharmaceutical form: Solution Route of administration: SC injection; Drug: MRI contrast-enhancing preparations; gadolinium compound, including but not limited to Magnevist, Multihance, Prohance, or Elucirem
Experimental: Intravenous (IV) SAR441344; SAR441344 IV	Drug: SAR441344 IV; Pharmaceutical form: Solution Route of administration: IV infusion; Drug: MRI contrast-enhancing preparations; gadolinium compound, including but not limited to Magnevist, Multihance, Prohance, or Elucirem
Experimental: Subcutaneous (SC) SAR441344; SAR441344 SC	Drug: SAR441344 SC; Pharmaceutical form: Solution Route of administration: SC injection; Drug: MRI contrast-enhancing preparations; gadolinium compound, including but not limited to Magnevist, Multihance, Prohance, or Elucirem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of New Gadolinium (Gd)-Enhancing T1--Hyperintense (GdE T1) Lesions at Week 12 Relative to Week 8 as Measured by Brain Magnetic Resonance Imaging (MRI)	Cranial (brain) MRI was performed to identify number of new GdE T1-hyperintense lesions at Week 12 relative to Week 8 MRI. Central review was used to identify new GdE T1 lesions not present at the previous MRI scans.	Week 8 and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of New or Enlarging T2 Lesions at Week 12 Relative to Week 8	Cranial (brain) MRI was performed to identify number of new or enlarging T2 lesions at Week 12 relative to Week 8.	Week 8 and Week 12
Mean Total Number of GdE T1 Lesions at Week 12	Cranial (brain) MRI was performed to identify total number of GdE T1 lesions at Week 12.	Baseline (Day 1) and Week 12
Double-Blind Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.	From first dose of study drug (Day 1) up to 12 weeks (DB TE period)
Double-Blind Period: Number of Participant With Anti-Drug Antibodies (ADAs) Against SAR441344	Blood samples were collected at specified timepoints to assess the presence of ADAs against SAR441344. Treatment-emergent ADA was defined as at least 1 treatment-induced/boosted ADA. Treatment-induced ADA was defined as ADA that developed during the TE period and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that was boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA are presented.	From first dose of study drug (Day 1) up to 12 weeks (DB TE period)
Maximum Plasma Concentration (Cmax) of SAR441344	Blood samples were collected at the specified timepoints for the assessment of Cmax. Cmax was assessed by a Bayesian approach using the population pharmacokinetic (PK) model.	After dose on Day 1 (first dose) and Weeks 8 (IV arm) and 10 (SC arm) (last dose)
Time to Maximum Plasma Concentration (Tmax) of SAR441344	Blood samples were collected at the specified timepoints for the assessment of tmax. tmax was assessed by a Bayesian approach using the population PK model.	After dose on Day 1 (first dose) and Weeks 8 (IV arm) and 10 (SC arm) (last dose)
Area Under the Curve Over the Dosing Interval (AUC0-tau) of SAR441344	Blood samples were collected at the specified timepoints for the assessment of AUC0-tau. AUC0-tau was assessed by a Bayesian approach using the population PK model.	After dose on Day 1 (first dose) and Weeks 8 (IV arm) and 10 (SC arm) (last dose)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Vermersch P, Granziera C, Mao-Draayer Y, Cutter G, Kalbus O, Staikov I, Dufek M, Saubadu S, Bejuit R, Truffinet P, Djukic B, Wallstroem E, Giovannoni G; Frexalimab Phase 2 Trial Group. Inhibition of CD40L with Frexalimab in Multiple Sclerosis. N Engl J Med. 2024 Feb 15;390(7):589-600. doi: 10.1056/NEJMoa2309439.

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2021
• Primary Completion (Actual): September 21, 2022
• Study Completion (Estimated): August 23, 2027

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Estimated): September 30, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis
• Other Study ID Numbers: ACT16877; 2020-004785-19 (EudraCT Number); U1111-1260-3962 (Registry Identifier: ICTRP); 2024-513527-17-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No