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

• ClinicalTrials.gov Identifier: NCT04879628
• Recruitment Status: Active, not recruiting
• First Posted: May 10, 2021
• Last Update Posted: February 21, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: May 6, 2021
• First Posted Date: May 10, 2021
• Last Update Posted Date: February 21, 2024
• Actual Study Start Date: June 7, 2021
• Actual Primary Completion Date: September 21, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 6, 2021)

Number of new Gadolinium (Gd)-enhancing T1-hyperintense (GdE T1) lesions [ Time Frame: At Week 12 ]

measured by brain magnetic resonance imaging (MRI)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 18, 2024)

• Number of new or enlarging T2 lesions [ Time Frame: At Week 12 ]
  measured by brain magnetic resonance imaging (MRI)
• Total number of GdE T1 lesions [ Time Frame: At Week 12 ]
  Total number of GdE T1 lesions at Week 12
• Adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Until Week 316 ]
  Number of participants with AEs and SAEs
• Antidrug antibodies (ADA) [ Time Frame: Until Week 316 ]
  Number of participants with ADA
• Pharmacokinetic (PK) parameters: Cmax [ Time Frame: Until Week 316 ]
  maximum concentration
• PK parameter: tmax [ Time Frame: Until Week 316 ]
  time to Cmax
• PK parameter: AUC0-tau [ Time Frame: Until Week 316 ]
  area under the curve over the dosing interval
• PK parameter: t1/2z [ Time Frame: Until Week 316 ]
  elimination half-life

Original Secondary Outcome Measures (submitted: May 6, 2021)

• Number of new or enlarging T2 lesions [ Time Frame: At Week 12 ]
  measured by brain magnetic resonance imaging (MRI)
• Total number of GdE T1 lesions [ Time Frame: At Week 12 ]
  Total number of GdE T1 lesions at Week 12
• Adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Until Week 88 ]
  Number of participants with AEs and SAEs
• Antidrug antibodies (ADA) [ Time Frame: Until Week 88 ]
  Number of participants with ADA
• Pharmacokinetic (PK) parameters: Cmax [ Time Frame: Until Week 88 ]
  maximum concentration
• PK parameter: tmax [ Time Frame: Until Week 88 ]
  time to Cmax
• PK parameter: AUC0-tau [ Time Frame: Until Week 88 ]
  area under the curve over the dosing interval
• PK parameter: t1/2z [ Time Frame: Until Week 88 ]
  elimination half-life

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

Descriptive Information

• Brief Title: Proof-of-concept Study for SAR441344 (Frexalimab) in Relapsing Multiple Sclerosis
• Official Title: 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

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

• 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
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Multiple Sclerosis

Intervention

• Drug: SAR441344 IV
  Pharmaceutical form: Solution Route of administration: IV infusion
• Drug: placebo IV
  Pharmaceutical form: Solution Route of administration: IV infusion
• Drug: SAR441344 SC
  Pharmaceutical form: Solution Route of administration: SC injection
• 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

Study Arms

• Experimental: Intravenous (IV) SAR441344
  SAR441344 IV
  Interventions:

  • Drug: SAR441344 IV
  • Drug: MRI contrast-enhancing preparations
• Placebo Comparator: IV Placebo
  Placebo IV
  Interventions:

  • Drug: placebo IV
  • Drug: MRI contrast-enhancing preparations
• Experimental: Subcutaneous (SC) SAR441344
  SAR441344 SC
  Interventions:

  • Drug: SAR441344 SC
  • Drug: MRI contrast-enhancing preparations
• Placebo Comparator: SC Placebo
  Placebo SC
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 6, 2022): 129
• Original Estimated Enrollment (submitted: May 6, 2021): 120
• Estimated Study Completion Date: August 23, 2027
• Actual Primary Completion Date: September 21, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria or with non-relapsing SPMS.
• The participant has conditions or situations that would adversely affect participation in this study.
• The participant has 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 has received any of the forbidden medications/treatments within the specified time frame before any baseline assessment.
• The participant has taken other investigational drug within 3 months or 5-half-live, whichever is longer, before the screening visit.
• The participant has an EDSS score >5.5 at the first screening visit.
• The participant has 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Bulgaria, Canada, Czechia, France, Germany, Russian Federation, Spain, Turkey, Ukraine, United States

Administrative Information

• NCT Number: NCT04879628
• Other Study ID Numbers: ACT16877; U1111-1260-3962 ( Registry Identifier: ICTRP ); 2020-004785-19 ( EudraCT Number )
• Has Data Monitoring Committee: No

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

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: February 2024