A Study to Evaluate Safety and Efficacy of BIIB091 in Participants With Relapsing Forms of Multiple Sclerosis (FUSION)

Biogen

Status and phase: Enrolling; Phase 2

Conditions: Relapsing Forms of Multiple Sclerosis

Treatments: Drug: BIIB091; Drug: DRF; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05798520

2022-502552-31 (Other Identifier)

257MS201

Details and patient eligibility

About

The primary objectives are to investigate the safety and tolerability of BIIB091 monotherapy in participants with relapsing multiple sclerosis (RMS) (Part 1), and to evaluate the effects of BIIB091 combination therapy with Diroximel Fumarate (DRF) compared with the DRF monotherapy arm, on the key Magnetic Resonance Imaging (MRI) measure of active Central Nervous System (CNS) inflammation (Part 2). The secondary objectives are to evaluate the effects of BIIB091 monotherapy on the MRI measures of active CNS inflammation, to evaluate the effects of BIIB091 combination therapy with DRF compared with the DRF monotherapy arm on additional MRI measures of active CNS inflammation, to investigate the safety and tolerability of BIIB091 combination therapy with DRF in participants with RMS.

Enrollment: 275 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Diagnosis of RMS [relapsing-remitting multiple sclerosis (RRMS) or active secondary progressive multiple sclerosis (SPMS)] in accordance with the 2017 Revised McDonald criteria.

2. Time since MS symptom onset is <20 years.

3. Must have expanded disability status scale (EDSS) score of 0 through 5.0 at screening and baseline.

4. Must have at least 1 of the following occurring prior to Baseline (Day 1):

   • ≥2 clinical relapses in the last 24 months (but not within 30 days prior to Baseline [Day 1]) with at least 1 relapse during the last 12 months prior to randomization.
   • ≥1 clinical relapse within the past 24 months (but not within 30 days prior to Baseline [Day 1]) and ≥1 new brain MRI lesion (Gd-positive and/or new or enlarging T2 hyperintense lesion) within the past 12 months prior to randomization. The screening MRI could be used to satisfy this criterion (if needed for inclusion, local reading is required). For new or enlarging T2 hyperintense lesions, the reference scan cannot be >12 months prior to randomization.
   • ≥1 GdE lesion on brain MRI within 6 months prior to randomization.

Key Exclusion Criteria:

1. Diagnosis of primary progressive multiple sclerosis (PPMS) in accordance with the 2017 Revised McDonald criteria.

2. An MS relapse that has occurred within 30 days prior to Baseline (Day 1) or the participant has not stabilized from a previous relapse at the time of screening.

3. History of severe allergic, anaphylactic reactions or hypersensitivity reaction to BIIB091 or DRF, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study, including the following:

   • Known hypersensitivity to any components of the study treatment
   • Known hypersensitivity to previous fumarate or bruton's tyrosine kinase (BTK) inhibitor treatments
   • History of hypersensitivity to parenteral administration of Gd-based contrast agents

4. Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within the past 4 weeks prior to Baseline.

5. History or positive test result at screening for human immunodeficiency virus (HIV).

6. Current or history of hepatitis C infection regardless of viral load.

7. Current or possible hepatitis B.

8. Current enrollment or plan to enroll in any other drug, biological, device, clinical study, or treatment with an investigational drug or approved therapy for investigational use within 90 days prior to randomization or 5 half-lives of the drug or therapy, whichever is longer.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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275 participants in 6 patient groups

Part 1: BIIB091 High Dose + Matching Placebo for DRF

Experimental group

Description:

Participants will receive BIIB091 high dose and matching placebo for DRF, orally, for up to 48 weeks.

Treatment:

Drug: Placebo

Drug: BIIB091

Part 1: BIIB091 Low Dose + Matching Placebo for DRF

Experimental group

Description:

Participants will receive BIIB091 low dose and matching placebo for DRF, orally, for up to 48 weeks.

Treatment:

Drug: Placebo

Drug: BIIB091

Part 1: DRF + Matching Placebo for BIIB091

Active Comparator group

Description:

Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.

Treatment:

Drug: Placebo

Drug: DRF

Part 2: BIIB091 + DRF Standard Dose

Experimental group

Description:

Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF standard dose, orally, for up to 48 weeks.

Treatment:

Drug: DRF

Drug: BIIB091

Part 2: BIIB091 + DRF Low Dose

Experimental group

Description:

Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF low dose, orally, for up to 48 weeks.

Treatment:

Drug: DRF

Drug: BIIB091

Part 2: DRF + Matching Placebo for BIIB091

Active Comparator group

Description:

Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.

Treatment:

Drug: Placebo

Drug: DRF