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

NCT04879628 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: ACT16877U1111-1260-39622024-513527-17-002020-004785-19
• Study Type: interventional
• Target: 129
• Locations: 10 countries
• Sites: 37

Brief Summary

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

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Mean 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

  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)

  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

  From first dose of study drug (Day 1) up to 12 weeks (DB TE period)

• Maximum Plasma Concentration (Cmax) of SAR441344

  After dose on Day 1 (first dose) and Weeks 8 (IV arm) and 10 (SC arm) (last dose)

Study Arms (4)

Intravenous (IV) SAR441344

EXPERIMENTAL

SAR441344 IV

Drug: SAR441344 IV; Drug: MRI contrast-enhancing preparations

IV Placebo

PLACEBO COMPARATOR

Placebo IV

Drug: placebo IV; Drug: MRI contrast-enhancing preparations

Subcutaneous (SC) SAR441344

EXPERIMENTAL

SAR441344 SC

Drug: SAR441344 SC; Drug: MRI contrast-enhancing preparations

SC Placebo

PLACEBO COMPARATOR

Placebo SC

Drug: placebo SC; Drug: MRI contrast-enhancing preparations

Interventions

SAR441344 IV DRUG

Pharmaceutical form: Solution Route of administration: IV infusion

Intravenous (IV) SAR441344

placebo IV DRUG

Pharmaceutical form: Solution Route of administration: IV infusion

IV Placebo

SAR441344 SC DRUG

Pharmaceutical form: Solution Route of administration: SC injection

Subcutaneous (SC) SAR441344

placebo SC DRUG

Pharmaceutical form: Solution Route of administration: SC injection

SC Placebo

MRI contrast-enhancing preparations DRUG

gadolinium compound, including but not limited to Magnevist, Multihance, Prohance, or Elucirem

IV Placebo; Intravenous (IV) SAR441344; SC Placebo; Subcutaneous (SC) SAR441344

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (37)

Center for Neurology and Spine- Site Number : 8400007

Phoenix, Arizona, 85032, United States

Location

University of South Florida Site Number : 8400001

Tampa, Florida, 33612, United States

Location

The Neurological Institute Site Number : 8400004

Charlotte, North Carolina, 28204, United States

Location

Medical College of Wisconsin- Site Number : 8400006

Milwaukee, Wisconsin, 53226, United States

Location

Investigational Site Number : 1000002

Pleven, 5809, Bulgaria

Location

Investigational Site Number : 1000003

Sofia, 1113, Bulgaria

Location

Investigational Site Number : 1000001

Sofia, 1407, Bulgaria

Location

Investigational Site Number : 1240001

Gatineau, Quebec, J8Y 1W2, Canada

Location

Investigational Site Number : 2030003

Brno, 65691, Czechia

Location

Investigational Site Number : 2030002

Hradec Králové, 50005, Czechia

Location

Investigational Site Number : 2030001

Jihlava, 58633, Czechia

Location

Investigational Site Number : 2030005

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number : 2030004

Teplice, 415 29, Czechia

Location

Investigational Site Number : 2500006

Calais, 62107, France

Location

Investigational Site Number : 2760012

Leipzig, 04103, Germany

Location

Investigational Site Number : 2760004

Münster, 48149, Germany

Location

Investigational Site Number : 6430002

Kazan', 420032, Russia

Location

Investigational Site Number : 6430007

Moscow, 117556, Russia

Location

Investigational Site Number : 6430006

Moscow, 117997, Russia

Location

Investigational Site Number : 6430001

Moscow, 127015, Russia

Location

Investigational Site Number : 6430003

Saint Petersburg, 194044, Russia

Location

Investigational Site Number : 6430005

Saint Petersburg, 197022, Russia

Location

Investigational Site Number : 6430004

Saint Petersburg, 197110, Russia

Location

Investigational Site Number : 6430008

Tyumen, 625000, Russia

Location

Investigational Site Number : 7240004

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240002

Vigo, 36312, Spain

Location

Investigational Site Number : 7920004

Eskişehir, 26040, Turkey (Türkiye)

Location

Investigational Site Number : 7920003

Istanbul, 34265, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

İzmit, 41380, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Mersin, 33070, Turkey (Türkiye)

Location

Investigational Site Number : 8040010

Dnipro, 49005, Ukraine

Location

Investigational Site Number : 8040006

Dnipro, 49089, Ukraine

Location

Investigational Site Number : 8040008

Ivano-Frankivsk, 76493, Ukraine

Location

Investigational Site Number : 8040002

Kyiv, 01135, Ukraine

Location

Investigational Site Number : 8040004

Lviv, 79013, Ukraine

Location

Investigational Site Number : 8040003

Odesa, 65025, Ukraine

Location

Investigational Site Number : 8040005

Vinnytsia, 21001, Ukraine

Location

Related Publications (1)

• 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.

  PMID: 38354138 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610 ext 6#

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A is a 12-week, double-blind, placebo-controlled part; Part B is an open-label SAR441344 treatment part.

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 10, 2021
• Study Start: June 7, 2021
• Primary Completion: September 21, 2022
• Study Completion (Estimated): August 23, 2027
• Last Updated: September 30, 2025
• Results First Posted: September 30, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

FR (1); CA (1); DE (2); CZ (5); TU (4); RU (8); ES (2); BU (3); US (4); UA (7)