Efficacy and safety study of frexalimab (SAR441344) in adults with relapsing forms of multiple sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

17 Oct 2024 → ongoing

Decision date (initial)

2024-04-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sanofi-Aventis Recherche & Développement

External identifiers

EU CT number

2023-504358-36-00

WHO UTN

U1111-1290-9326

ClinicalTrials.gov

NCT06141473

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacodynamic, Therapy, Safety

To assess the efficacy of frexalimab compared to a daily dose of 14 mg teriflunomide measured by ARR in participants with relapsing forms of MS

Secondary objectives 4

1. To assess the efficacy of frexalimab compared to teriflunomide on disability worsening, MRI lesions, cognitive performance, physical function, and quality of life
2. To evaluate the safety and tolerability of frexalimab in participants with relapsing forms of MS
3. To evaluate pharmacodynamics of frexalimab in participants with relapsing forms of MS
4. To evaluate pharmacokinetics of frexalimab in participants with relapsing forms of MS

Conditions and MedDRA coding

multiple sclerosis

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share 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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria.
2. The participant has an EDSS score ≤5.5 at the first visit (Screening Visit)
3. 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.
4. 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 8

1. The participant has been diagnosed with PPMS according to the 2017 revision of the McDonald diagnostic criteria
2. The participant has a history of infection or may be at risk for infection.
3. The presence of psychiatric disturbance or substance abuse.
4. 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.
5. Current hypogammaglobulinemia defined by Ig levels below the LLN at Screening or a history of primary hypogammaglobulinemia
6. 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.
7. The participant has had a relapse in the 30 days prior to randomization.
8. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses

Secondary endpoints 15

1. Time to onset of composite confirmed disability worsening (cCDW)
2. Time to onset of cCDW, confirmed over 3 months
3. Time to onset of individual components of the composite, confirmed over 3-months or 6- months
4. Time to onset of confirmed disability improvement (CDI)
5. Progression independent of relapse activity defined as the time to onset of 6-month cCDW
6. Total number of new and/or enlarging T2-hyperintense lesions as detected by MRI
7. Total number of new Gd-enhancing T1-hyperintense lesions per scan as detected by MRI
8. Percent change in brain volume loss as detected by brain MRI scans at the EOS compared to Month 6
9. Change in cognitive function at the EOS compared to baseline as assessed by the symbol digit modalities test (SDMT)
10. Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time
11. Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue MS-8 over time
12. Adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs, safety scales, and potentially clinically significant abnormality (PCSAs) in laboratory tests, ECG, and vital signs during the study period
13. Antidrug antibodies (ADAs) over time
14. Change from baseline in plasma neurofilament light chain (NfL) levels over time
15. Frexalimab plasma concentration over time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 5

Placebo 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 19

Locations

18 EU/EEA countries · 68 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 276 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

12 submissions — initial application plus substantial / non-substantial modifications