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)

NCT05798520 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 257MS2012022-502552-31
• Study Type: interventional
• Target: 127
• Locations: 10 countries
• Sites: 77

Brief Summary

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.

Conditions

Relapsing Forms of Multiple Sclerosis

Keywords

Multiple Sclerosis; Diroximel fumarate; BIIB091

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• 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

Study Arms (6)

Part 1: BIIB091 High Dose + Matching Placebo for DRF

EXPERIMENTAL

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

Drug: BIIB091; Drug: Placebo

Part 1: BIIB091 Low Dose + Matching Placebo for DRF

EXPERIMENTAL

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

Drug: BIIB091; Drug: Placebo

Part 1: DRF + Matching Placebo for BIIB091

ACTIVE COMPARATOR

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

Drug: DRF; Drug: Placebo

Part 2: BIIB091 + DRF Standard Dose

EXPERIMENTAL

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

Drug: BIIB091; Drug: DRF

Part 2: BIIB091 + DRF Low Dose

EXPERIMENTAL

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

Drug: BIIB091; Drug: DRF

Part 2: DRF + Matching Placebo for BIIB091

ACTIVE COMPARATOR

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

Drug: DRF; Drug: Placebo

Interventions

BIIB091 DRUG

Administered as specified in the treatment arm.

Part 1: BIIB091 High Dose + Matching Placebo for DRF; Part 1: BIIB091 Low Dose + Matching Placebo for DRF; Part 2: BIIB091 + DRF Low Dose; Part 2: BIIB091 + DRF Standard Dose

DRF DRUG

Administered as specified in the treatment arm.

Part 1: DRF + Matching Placebo for BIIB091; Part 2: BIIB091 + DRF Low Dose; Part 2: BIIB091 + DRF Standard Dose; Part 2: DRF + Matching Placebo for BIIB091

Placebo DRUG

Administered as specified in the treatment arm.

Part 1: BIIB091 High Dose + Matching Placebo for DRF; Part 1: BIIB091 Low Dose + Matching Placebo for DRF; Part 1: DRF + Matching Placebo for BIIB091; Part 2: DRF + Matching Placebo for BIIB091

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of RMS \[relapsing-remitting multiple sclerosis (RRMS) or active secondary progressive multiple sclerosis (SPMS)\] in accordance with the 2017 Revised McDonald criteria.
• Time since MS symptom onset is \<20 years.
• Must have expanded disability status scale (EDSS) score of 0 through 5.0 at screening and baseline.
• 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 GdE lesion on brain MRI within 6 months prior to randomization.

You may not qualify if:

• Diagnosis of primary progressive multiple sclerosis (PPMS) in accordance with the 2017 Revised McDonald criteria.
• 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.
• 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
• Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within the past 4 weeks prior to Baseline.
• History of human immunodeficiency virus (HIV) infection or a positive or indeterminate test result at screening for HIV.
• Current or history of hepatitis C infection regardless of viral load.
• Current or history of hepatitis B infection.
• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (77)

HonorHealth Neurology

Scottsdale, Arizona, 85251, United States

Location

Alta Bates Summit Medical Center

Berkeley, California, 94705, United States

Location

University of California at Irvine Medical Center

Orange, California, 92868, United States

Location

University of Colorado School of Medic

Aurora, Colorado, 80045, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Vero Beach Neurology and Research Institute

Vero Beach, Florida, 32960, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46804, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

International Neurorehabilitation Institute

Lutherville, Maryland, 21093, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Holy Name

Teaneck, New Jersey, 07666, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131-0001, United States

Location

South Shore Neurologic Associates, P.C.

Patchogue, New York, 11772, United States

Location

Wake Forest University - School of Medicine - Central

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati Physicians Company

Cincinnati, Ohio, 45267, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Boster Center for Multiple Sclerosis

Columbus, Ohio, 43235, United States

Location

Neurology Clinic, PC

Cordova, Tennessee, 38018, United States

Location

Vanderbilt MS Center

Nashville, Tennessee, 37215, United States

Location

The University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229-3900, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

'MHAT Avis - Medica' OOD

Pleven, 5800, Bulgaria

Location

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, 5800, Bulgaria

Location

UMHAT 'Sv. Georgi', EAD

Plovdiv, 4002, Bulgaria

Location

MHATNP 'Sv.Naum', EAD

Sofia, 1113, Bulgaria

Location

University First MHAT-Sofia, 'St. Joan Krastitel' EAD

Sofia, 1142, Bulgaria

Location

Acibadem City Clinic Tokuda University Hospital Ead

Sofia, 1407, Bulgaria

Location

DCC Neoclinic EAD

Sofia, 1408, Bulgaria

Location

UMHAT "Sv. Ivan Rilski", EAD

Sofia, 1431, Bulgaria

Location

Diagnostic Consultation Center CONVEX EOOD

Sofia, 1680, Bulgaria

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 65691, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Nemocnice Jihlava p.o.

Jihlava, 58633, Czechia

Location

Fakultni Thomayerova nemocnice

Praha 4-Krc, 14059, Czechia

Location

Krajska zdravotni a.s. - Nemocnice Teplice o.z.

Teplice, 41529, Czechia

Location

Studienzentrum fur Neurologie und Psychiatrie

Böblingen, Baden-Wurttemberg, 71034, Germany

Location

Klinikum Bayreuth GmbH- Hohe Warte

Bayreuth, Bavaria, 95445, Germany

Location

Neuropraxis Muenchen Sued

Unterhaching, Bavaria, 82008, Germany

Location

Universitaetsklinikum Duesseldorf AoeR

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

ZNS - Zentrum fuer Neurologisch-Psychiatrische Studien

Siegen, North Rhine-Westphalia, 57076, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 01307, Germany

Location

I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo

Pozzilli, Isernia, 86077, Italy

Location

Fondazione Istituto G.Giglio di Cefalù

Cefalù, Palermo, 90015, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"

Naples, 80138, Italy

Location

Fondazione Istituto Neurologico Casimiro Mondino

Pavia, 27100, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Roma, 00133, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza

Roma, 00161, Italy

Location

COPERNICUS Podmiot Leczniczy Sp. z o. o.,

Gdansk, 80-803, Poland

Location

Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. Jana Pawla II

Grodzisk Mazowiecki, 05-825, Poland

Location

Centrum Medyczne Pratia Katowice

Katowice, 40-081, Poland

Location

M.A. - LEK A.M.Maciejowscy SC.

Katowice, 40-571, Poland

Location

Nzoz Novo-Med

Katowice, 40-650, Poland

Location

Resmedica Sp.z o.o

Kielce, 25-726, Poland

Location

Szpital Uniwersytecki w Krakowie

Krakow, 31-503, Poland

Location

Centrum Neurologii K. Selmaj

Lodz, 90-324, Poland

Location

Instytut Zdrowia dr Boczarska-Jedynak sp.z.o.o, Sp.K

Oświęcim, 32-600, Poland

Location

Med-Polonia Sp. z o.o.

Poznan, 60-693, Poland

Location

NZOZ 'NEURO-KARD', 'Ilkowski i Partnerzy' Sp. Partn. Lek.

Poznan, 61-853, Poland

Location

Nzoz Palomed

Rzeszów, 35-323, Poland

Location

NeuroProtect Sp. z o.o.

Warsaw, 01-684, Poland

Location

Wielospecjalistyczne Centrum Medyczne Ibismed

Zabrze, 41-800, Poland

Location

Caribbean Center for Clinical Research

Guaynabo, San Juan, 00968, Puerto Rico

Location

S.C Neurocity S.R.L

Bucharest, 11302, Romania

Location

Spitalul Universitar de Urgenta Elias

Bucharest, 11461, Romania

Location

S.C Clubul Sanatatii SRL

Campulung Muscel, 115100, Romania

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario Virgen de la Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14011, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Ospedale Regionale di Lugano

Lugano, Canton Ticino, 6903, Switzerland

Location

Inselspital - Universitaetsspital Bern

Bern, 3010, Switzerland

Location

Universitaetsspital Zuerich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

BIIB091

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 4, 2023
• Study Start: July 25, 2023
• Primary Completion: February 10, 2026
• Study Completion: February 10, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

PR (1); PL (14); DE (6); IT (7); US (23); CZ (5); RO (3); ES (6); CH (3); BU (9)