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

JRCT ID: jRCT2021240004

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: 1400
• 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: Teriflunomide (Aubagio)
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: Frexalimab-matching placebo
Pharmaceutical form: Solution for infusion, Route of administration: IV infusion
Drug: Teriflunomide-matching placebo
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: MRI contrast-enhancing agents
Route of administration: IV, as per respective label.
Drug: Cholestyramine
Route of administration: oral, 8 g 3 times daily for 11 days for accelerated elimination procedure (4 g 3 times daily for 11 days in case of intolerance). The teriflunomide local label should be followed.
Drug: Activated charcoal
Route of administration: oral, 50 g every 12 hours for 11 days for accelerated elimination procedure. The teriflunomide local label should be followed.

Study arms:
- Frexalimab group
Participants will receive Frexalimab infusion and Teriflunomide-matching placebo tablet.
Drug: Frexalimab, Teriflunomide-matching placebo tablet, MRI contrast-enhancing agents, Cholestyramine, Activated charcoal
- Teriflunomide group
Participants will receive teriflunomide tablet and Frexalimab-matching placebo infusion.
Drug: Teriflunomide, Frexalimab-matching placebo infusion, MRI contrast-enhancing agents, Cholestyramine, Activated charcoal

Outcome(s)

Primary Outcome

1. Annualized relapse rate (ARR) during the study period assessed by protocol defined adjudicated relapses
[Time Frame: Until Week 156]
ARR during the study period assessed by protocol-defined adjudicated relapses. This endpoint will be analyzed in the intent to treat population of each study using a negative binomial model with the total number of adjudicated relapses per participant occurring during the observation period as the response variable and with terms for treatment group, Gadolinium (Gd)-enhancing T1 lesions at baseline (presence, absence), expanded disability status scale (EDSS) strata (<4, >=4), and geographical region (US, non-US).

Secondary Outcome

1. Time to onset of composite confirmed disability worsening (cCDW)
[Time Frame: Until Week 156]
confirmed over 6 months as assessed by the composite of:
- increase from the baseline EDSS score of >=1.5 points when the baseline is 0, or >=1.0 point when the baseline is 0.5 to <=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
2. Time to onset of cCDW, confirmed over 3 months
[Time Frame: Until Week 156]
3. Time to onset of individual components of the composite, confirmed over 3-months or 6-months
[Time Frame: Until Week 156]
4. Time to onset of confirmed disability improvement
[Time Frame: Until Week 156]
defined as EDSS score of >=1.0 or >=0.5 points when the baseline is >=2 to <=5.5 or >5.5 points, respectively, confirmed over 6 months. No improvement possible for 0 to 1.5 points
5. Progression independent of relapse activity defined as the time to onset of 6-month cCDW
[Time Frame: Until Week 156]
defined by either no prior relapse or an onset more than 90 days after the start date of the last investigator-reported relapse
6. Total number of new and/or enlarging T2-hyperintense lesions as detected by MRI
[Time Frame: Until Week 156]
defined as the sum of the individual number of new and/or enlarging T2 lesions at all scheduled visits starting after baseline up to and including the end of study (EOS) visit
7. Total number of new Gd-enhancing T1-hyperintense lesions per scan as detected by MRI
[Time Frame: Until Week 156]
defined as the sum of the individual number of new Gd enhancing T1-hyperintense lesions at all scheduled visits starting after baseline up to and including the EOS visit divided by the number of scans
8. Percent change in brain volume loss as detected by brain MRI scans at the EOS compared to Month 6
[Time Frame: From Week 24 to Week 156]
9. Change in cognitive function at the EOS compared to baseline as assessed by the symbol digit modalities test
[Time Frame: From baseline to Week 156]
10. Change from baseline in multiple sclerosis impact scale 29 version 2 questionnaire scores over time
[Time Frame: From baseline to Week 156]
11. Change from baseline in patient reported outcome measurement information system Fatigue MS-8 over time
[Time Frame: Until Week 156]
12. Adverse events (AEs), serious adverse events (SAEs), AEs leading to permanent study intervention discontinuation, AEs of special interest (AESIs), safety scales, and potentially clinically significant abnormality in laboratory tests, electrocardiogram (ECG), and vital signs during the study period
[Time Frame: Until Week 168]
13. Antidrug antibodies over time
[Time Frame: Until Week 156]
14. Change from baseline in plasma neurofilament light chain levels over time
[Time Frame: Until Week 144]
15. Frexalimab plasma concentration over time
[Time Frame: Until Week 144]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 55age old
• Gender: Both

Include criteria

- The participant must have been diagnosed with relapsing multiple sclerosis (RMS) according to the 2017 revision of the McDonald diagnostic criteria.
- The participant has an expanded disability status scale (EDSS) score <=5.5 at the first visit (Screening Visit).
- 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 Gadolinium (Gd) enhancing lesion on a magnetic resonance imaging (MRI) scan within the previous year.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclude criteria

- The participant has been diagnosed with primary progressive multiple sclerosis (MS) according to the 2017 revision of the McDonald diagnostic 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 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 had a relapse in the 30 days prior to randomization.
- 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.

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT06141473,2023-504358-36