Efficacy and safety study of frexalimab (SAR441344) in adults with nonrelapsing secondary progressive 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

11 Dec 2024 → ongoing

Decision date (initial)

2024-11-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-504359-29-01

WHO UTN

U1111-1280-7114

ClinicalTrials.gov

NCT06141486

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic, Efficacy, Therapy

To assess the efficacy of frexalimab compared to placebo in delaying disability progression in nrSPMS

Secondary objectives 4

1. To assess the efficacy of frexalimab compared to placebo on clinical endpoints, MRI lesions, cognitive performance, physical function, and quality of life
2. To evaluate safety and tolerability of frexalimab
3. To evaluate pharmacodynamics of frexalimab in participants with nrSPMS
4. To evaluate pharmacokinetics of frexalimab in nrSPMS

Conditions and MedDRA coding

Multiple sclerosis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002945-PIP02-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Participant must have a previous diagnosis of RRMS in accordance with the 2017 revised McDonald criteria.
2. Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013 endorsed by an Adjudication Committee.
3. Participant must have documented evidence of disability progression observed during the 12 months before screening. Eligibility will be analyzed by an Adjudication Committee.
4. Absence of clinical relapses for at least 24 months.
5. The participant must have an EDSS score at screening from 3.0 to 6.5 points, inclusive.
6. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
7. For patients eligible to be treated with siponimod: 1) does not tolerate it due to side effects or safety reasons, or 2) has failed siponimod treatment due to perceived lack of efficacy, or 3) has declined siponimod treatment.

Exclusion criteria 7

1. The participant has a history of infection or may be at risk for infection.
2. The presence of psychiatric disturbance or substance abuse.
3. 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.
4. History or current hypogammaglobulinemia defined by values below the lower limit of normal (LLN).
5. 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.
6. The participant has sensitivity to any of the study interventions, or components thereof, or has a drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
7. The participant was previously exposed to frexalimab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to onset of composite confirmed disability progression (cCDP) confirmed over 6 months

Secondary endpoints 14

1. Time to onset of composite cCDP confirmed over 3 months in the double-blind treatment period
2. Time to onset of CDP confirmed over 3-months or 6 months in the double-blind treatment period
3. Time to onset of confirmed disability improvement (CDI) in the double-blind treatment period
4. Number of new and/or enlarging T2 hyperintense lesions per scan as detected by MRI
5. Percent change in brain volume loss as detected by MRI scans at the end of double-blind treatment period compared to Month 6
6. Change in cognitive function at the end of double-blind treatment period compared to baseline as assessed by symbol digit modalities test (SDMT)
7. Change from baseline in multiple sclerosis impact scale 29 version 2 (MSIS-29v2) questionnaire scores over time in the double-blind treatment period
8. Change from baseline in patient reported outcome measurement information system (PROMIS) Fatigue multiple sclerosis (MS)-8a over time in the double-blind treatment period
9. Annualized relapse rate during the double-blind treatment period assessed by protocol defined adjudicated relapses
10. Adverse events, SAEs, AEs leading to permanent study intervention discontinuation, AESIs, and PCSAs in laboratory tests, ECG, and vital signs during the study period
11. Antidrug antibody over time
12. Change from baseline in serum Ig levels over time
13. Change from baseline in plasma neurofilament light chain (NfL) levels over time in the double-blind treatment period
14. Frexalimab plasma concentration over time in the double-blind treatment period

Investigational products

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

Test 1

Placebo 1

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 20

Locations

13 EU/EEA countries · 128 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 217 files

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

Application history

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