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

JRCT ID: jRCT2021240003

Registered date:12/04/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Multiple sclerosis
• Date of first enrollment: 22/04/2024
• Target sample size: 858
• Countries of recruitment: United States,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

Drug: Frexalimab (SAR441344)
Pharmaceutical form: Solution for infusion, Route of administration: Intravenous (IV) infusion
Drug: Placebo
Pharmaceutical form: Solution for infusion, Route of administration: IV infusion
Drug: magnetic resonance imaging (MRI) contrast-enhancing agents
Route of administration: IV, as per respective label

Study Arm:
- Frexalimab group: Frexalimab IV administration
Drug: Frexalimab, MRI contrast-enhancing agents
- Placebo group: Frexalimab-matching placebo
Drug: Placebo, MRI contrast-enhancing agents

Outcome(s)

Primary Outcome

1. Time to onset of composite confirmed disability progression (cCDP) confirmed over 6 months
[Time Frame: Until Week 204]
Defined as Increase from the baseline expanded disability status scale (EDSS) score of >=1.0 point when the baseline is <5.5, or >=0.5 point when the baseline is >=5.5, OR Increase of >=20% from the baseline time in the 9 hole peg test (9HPT), OR Increase of >=20% from the baseline time in the timed 25 foot walk (T25FW) test

Secondary Outcome

1. Time to onset of composite cCDP confirmed over 3 months
[Time Frame: Until Week 204]
2. Time to onset of individual components of the composite, confirmed over 3-months or 6-months
[Time Frame: Until Week 204]
3. Time to onset of confirmed disability improvement
[Time Frame: Until Week 204]
defined as decrease from the baseline EDSS score of >=1.0 or >= 0.5 points when baseline is <=5.5 or >5.5 points, respectively, confirmed over 6 months.
4. Number of new and/or enlarging T2-hyperintense lesions per scan as detected by MRI
[Time Frame: Until Week 204]
defined as the sum of the individual number of new and/or enlarging T2-hyperintense lesions at all scheduled visits starting after baseline up to and including the end of study (EOS) visit
5. Percent change in brain volume loss as detected by MRI scans at the EOS compared to Month 6
[Time Frame: From Week 24 to Week 204]
6. Change in cognitive function at the EOS compared to baseline as assessed by symbol digit modalities test
[Time Frame: Baseline, Until Week 204]
7. Change from baseline in multiple sclerosis impact scale 29 version 2 questionnaire scores over time
[Time Frame: Baseline, Until Week 204]
8. Change from baseline in patient reported outcome measurement information system Fatigue multiple sclerosis (MS)-8a over time
[Time Frame: Baseline, Until Week 204]
9. Annualized relapse rate during the study period assessed by protocol defined adjudicated relapses
[Time Frame: Until Week 204]
10. Adverse events (AEs), serious adverse events (SAEs), AEs leading to permanent study intervention discontinuation, AEs of special interest (AESIs), and potentially clinically significant abnormalities in laboratory tests, electrocardiogram (ECG), and vital signs during the study period
[Time Frame: Until Week 204]
11. Antidrug antibody over time
[Time Frame: Until Week 204]
12. Change from baseline in serum immunoglobulin levels over time
[Time Frame: Until Week 204]
13. Change from baseline in plasma neurofilament light chain levels over time
[Time Frame: Until Week 204]
14. Frexalimab plasma concentration over time
[Time Frame: Until Week 204]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 60age old
• Gender: Both

Include criteria

- Participant must have a previous diagnosis of relapsing remitting multiple sclerosis (RRMS) in accordance with the 2017 revised McDonald criteria.
- Participant must have a current diagnosis of secondary progressive multiple sclerosis (SPMS) in accordance with the clinical course criteria revised in 2013 endorsed by an Adjudication Committee.
- Participant must have documented evidence of disability progression observed during the 12 months before screening. Eligibility will be analyzed by an Adjudication Committee.
- Absence of clinical relapses for at least 24 months.
- The participant must have an expanded disability status scale (EDSS) score at screening from 3.0 to 6.5 points, inclusive.
- Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclude criteria

- The participant has a history of infection or may be at risk for infection.
- The presence of psychiatric disturbance or substance abuse.
- History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, and/or antiphospholipid syndrome and any participants requiring antithrombotic treatment.
- History or current hypogammaglobulinemia defined by values below the lower limit of normal (LLN).
- A history or presence of disease that can mimic multiple sclerosis (MS) symptoms, such as, but not limited to neuromyelitis optica spectrum disorder, systemic lupus erythematosus, Sjogren's syndrome, acute disseminated encephalomyelitis, and myasthenia gravis.
- 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.
- The participant was previously exposed to frexalimab.

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

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT06141486,2023-504359-29