A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (FUSION)

A 2-Part, Multicenter, Randomized, Blinded, Active-Controlled Phase 2 Study to Sequentially Evaluate the Safety and Efficacy of BIIB091 Monotherapy and BIIB091 Combination Therapy With Diroximel Fumarate in Participants With Relapsing Forms of Multiple Sclerosis

In this study, researchers will learn more about a study drug called BIIB091 in participants with MS who may be experiencing relapses. It is a 2-part study.

In Part 1, one set of participants will take either BIIB091 or diroximel fumarate (DRF). In Part 2, a different set of participants will take either a combination of BIIB091 and DRF or DRF alone.

The goal of the study is to learn more about the safety of BIIB091 and to compare the effects of the study drug when taken alone or together with DRF.

The main question researchers are trying to answer are:

• How many participants have new or worsening medical problems (adverse events) after taking BIIB091 or DRF?
• How many new areas of inflammation occur in the brain after treatment with BIIB091 and DRF?

Researchers will use magnetic resonance imaging (MRI) scans to compare images of the brain before and after treatment. They will also explore the effect of BIIB091 and DRF on the heart using electrocardiograms (ECGs).

The study will be done as follows:

• After screening, participants who joined Part 1 will be randomly assigned to receive either a high or low dose of BIIB091, or the standard dose of DRF.
• The results of Part 1 will be used to choose the best dose of BIIB091 to use in Part 2.
• Participants who join Part 2 will be randomly assigned to receive either a standard dose of DRF, a combo of BIIB091 and the standard dose of DRF, or a combo of BIIB91 with a low dose of DRF.
• Neither the researchers nor the participants will know which drug or dose the participants will receive in either part of the study.
• The treatment period will last 48 weeks in each part of the study. Participants will take the drugs by mouth 2 times a day.
• Each part will also have a follow-up safety period that lasts up to 2 weeks.
• In total, participants in each part will have 20 study visits, or more if they have a relapse. The total study duration for participants will be up to 54 weeks.

Study Overview

• Status: Completed
• Conditions: Relapsing Forms of Multiple Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: BIIB091; Drug: DRF

Detailed Description

The primary objectives of this study are to investigate the safety and tolerability of BIIB091 monotherapy in participants with relapsing multiple sclerosis (RMS) in Part 1 and to evaluate the effects of BIIB091 combination therapy with DRF compared with the DRF monotherapy arm on the key MRI measure of active central nervous system (CNS) inflammation in Part 2.

The secondary objectives of Part 1 of the study are to evaluate the effects of BIIB091 monotherapy on the MRI measures of active CNS inflammation and to assess the effect of BIIB091 monotherapy on QTc and other ECG parameters. The secondary objectives of Part 2 are to evaluate the effects of BIIB091 combination therapy with DRF compared with the DRF monotherapy arm on additional MRI measures of active CNS inflammation, the safety and tolerability of BIIB091 combination therapy with DRF in participants with RMS, and the effect of BIIB091 combination therapy with DRF on QTc and other ECG parameters.

Part 1 of the study was concluded normally. Sponsor decision was to not conduct part 2.

• Study Type: Interventional
• Enrollment (Actual): 127
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT 'Dr. Georgi Stranski', EAD
  • Pleven, Bulgaria, 5800
    • 'MHAT Avis - Medica' OOD
  • Plovdiv, Bulgaria, 4002
    • Umhat 'Sv. Georgi', Ead
  • Sofia, Bulgaria, 1431
    • UMHAT "Sv. Ivan Rilski", EAD
  • Sofia, Bulgaria, 1680
    • Diagnostic Consultation Center CONVEX EOOD
  • Sofia, Bulgaria, 1113
    • MHATNP 'Sv.Naum', EAD
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda University Hospital EAD
  • Sofia, Bulgaria, 1142
    • University First MHAT-Sofia, 'St. Joan Krastitel' EAD
  • Sofia, Bulgaria, 1408
    • DCC Neoclinic EAD
• Czechia
  • Brno, Czechia, 65691
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Králové, Czechia, 50005
    • Fakultni Nemocnice Hradec Kralove
  • Jihlava, Czechia, 58633
    • Nemocnice Jihlava p.o.
  • Praha 4-Krc, Czechia, 14059
    • Fakultni Thomayerova nemocnice
  • Teplice, Czechia, 41529
    • Krajska zdravotni a.s. - Nemocnice Teplice o.z.
• Germany
  • Dresden, Germany, 01307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Baden-Wurttemberg
    • Böblingen, Baden-Wurttemberg, Germany, 71034
      • Studienzentrum für Neurologie und Psychiatrie
  • Bavaria
    • Bayreuth, Bavaria, Germany, 95445
      • Klinikum Bayreuth GmbH- Hohe Warte
    • Unterhaching, Bavaria, Germany, 82008
      • Neuropraxis Muenchen Sued
  • North Rhine-Westphalia
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Universitaetsklinikum Duesseldorf AoeR
    • Siegen, North Rhine-Westphalia, Germany, 57076
      • ZNS - Zentrum fuer Neurologisch-Psychiatrische Studien
• Italy
  • Genova, Italy, 16132
    • IRCCS Ospedale Policlinico San Martino
  • Napoli, Italy, 80138
    • Azienda Ospedaliera Universitaria- Università Degli Studi Della Campania "Luigi Vanvitelli"
  • Pavia, Italy, 27100
    • Fondazione Istituto Neurologico Casimiro Mondino
  • Roma, Italy, 00133
    • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  • Roma, Italy, 00161
    • Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
  • Isernia
    • Pozzilli, Isernia, Italy, 86077
      • I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
  • Palermo
    • Cefalù, Palermo, Italy, 90015
      • Fondazione Istituto G.Giglio di Cefalù
• Poland
  • Gdansk, Poland, 80-803
    • COPERNICUS Podmiot Leczniczy Sp. z o. o.,
  • Grodzisk Mazowiecki, Poland, 05-825
    • Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. Jana Pawla II
  • Katowice, Poland, 40-081
    • Centrum Medyczne Pratia Katowice
  • Katowice, Poland, 40-571
    • M.A. - LEK A.M.Maciejowscy SC.
  • Katowice, Poland, 40-650
    • Nzoz Novo-Med
  • Kielce, Poland, 25-726
    • Resmedica Sp.z o.o
  • Krakow, Poland, 31-503
    • Szpital Uniwersytecki w Krakowie
  • Lodz, Poland, 90-324
    • Centrum Neurologii K. Selmaj
  • Oświęcim, Poland, 32-600
    • Instytut Zdrowia dr Boczarska-Jedynak sp.z.o.o, Sp.K
  • Poznan, Poland, 60-693
    • Med-Polonia Sp. z o.o.
  • Poznan, Poland, 61-853
    • NZOZ 'NEURO-KARD', 'Ilkowski i Partnerzy' Sp. Partn. Lek.
  • Rzeszów, Poland, 35-323
    • Nzoz Palomed
  • Warsaw, Poland, 01-684
    • NeuroProtect Sp. z o.o.
  • Zabrze, Poland, 41-800
    • Wielospecjalistyczne Centrum Medyczne Ibismed
• Puerto Rico
  • San Juan
    • Guaynabo, San Juan, Puerto Rico, 00968
      • Caribbean Center for Clinical Research
• Romania
  • Bucharest, Romania, 11461
    • Spitalul Universitar de Urgenta Elias
  • Bucharest, Romania, 11302
    • S.C Neurocity S.R.L
  • Campulung Muscel, Romania, 115100
    • S.C Clubul Sanatatii SRL
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Córdoba, Spain, 14011
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quirónsalud Madrid
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Universitario Virgen de La Arrixaca
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital - Universitaetsspital Bern
  • Zurich, Switzerland, 8091
    • Universitaetsspital Zuerich
  • Canton Ticino
    • Lugano, Canton Ticino, Switzerland, 6903
      • Ospedale Regionale di Lugano
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Neurology
  • California
    • Berkeley, California, United States, 94705
      • Alta Bates Summit Medical Center
    • Orange, California, United States, 92868
      • University of California at Irvine Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medic
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
    • Tampa, Florida, United States, 33612
      • University of South Florida
    • Vero Beach, Florida, United States, 32960
      • Vero Beach Neurology and Research Institute
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Neurological Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute, Inc.
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • International Neurorehabilitation Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • University of New Mexico
  • New York
    • Patchogue, New York, United States, 11772
      • South Shore Neurologic Associates, P.C.
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University - School of Medicine - Central
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Physicians Company
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43235
      • The Boster Center for Multiple Sclerosis
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, PC
    • Nashville, Tennessee, United States, 37215
      • Vanderbilt MS Center
  • Texas
    • San Antonio, Texas, United States, 78229-3900
      • The University of Texas Health Science Center San Antonio
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 of human immunodeficiency virus (HIV) infection or a positive or indeterminate test result at screening for HIV.
6. Current or history of hepatitis C infection regardless of viral load.
7. Current or history of hepatitis B infection.
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: BIIB091 High Dose + Matching Placebo for DRF; Participants will receive BIIB091 high dose and matching placebo for DRF, orally, for up to 48 weeks.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB091; Administered as specified in the treatment arm.
Experimental: Part 1: BIIB091 Low Dose + Matching Placebo for DRF; Participants will receive BIIB091 low dose and matching placebo for DRF, orally, for up to 48 weeks.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: BIIB091; Administered as specified in the treatment arm.
Active Comparator: Part 1: DRF + Matching Placebo for BIIB091; Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: DRF; Administered as specified in the treatment arm.
Experimental: Part 2: BIIB091 + DRF Standard Dose; Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF standard dose, orally, for up to 48 weeks.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: DRF; Administered as specified in the treatment arm.
Experimental: Part 2: BIIB091 + DRF Low Dose; Participants will receive selected dose of BIIB091 (based on Part 1 data) and DRF low dose, orally, for up to 48 weeks.	Drug: BIIB091; Administered as specified in the treatment arm.; Drug: DRF; Administered as specified in the treatment arm.
Active Comparator: Part 2: DRF + Matching Placebo for BIIB091; Participants will receive DRF standard dose and matching placebo for BIIB091, orally, for up to 48 weeks.	Drug: Placebo; Administered as specified in the treatment arm.; Drug: DRF; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product or auxiliary medicinal product, whether or not related to the medicinal (investigational) product or auxiliary medicinal product.	Day 1 up to Week 50
Part 1: Number of Participants With Serious Adverse Events (SAEs)	SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.	From signing the informed consent form (ICF) to Week 50
Part 2: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions		Week 8 to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions		Week 8 to Week 16
Part 1: Cumulative Number of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Part 1: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Part 1: Mean Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF), RR, PR, QRS, and QT Intervals		Up to Week 50
Part 1: Number of Participants With Change From Baseline in Heart Rate		Up to Week 50
Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities		Up to Week 50
Part 2: Cumulative Number of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Part 2: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Part 2: Number of Participants With AEs	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product or auxiliary medicinal product, whether or not related to the medicinal (investigational) product or auxiliary medicinal product.	Day 1 up to Week 50
Part 2: Number of Participants With SAEs	SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.	From signing of ICF up to Week 50
Part 2: Number of Participants With Change From Baseline in QTcF, RR, PR, QRS, and QT intervals		Up to Week 50
Part 2: Number of Participants With Change From Baseline in Heart Rate		Up to Week 50
Part 2: Number of Participants With ECG Abnormalities as Assessed by 12-Lead ECG Measurements		Up to Week 50

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2023
• Primary Completion (Actual): February 10, 2026
• Study Completion (Actual): February 10, 2026

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): April 4, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Diroximel fumarate; BIIB091
• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; BIIB091
• Other Study ID Numbers: 257MS201; 2022-502552-31 (Other Identifier: EU CT NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No