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

Relapsing Forms of Multiple Sclerosis Clinical Trial

— FUSION  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05798520
• Other study ID #: 257MS201
• Secondary ID: 2022-502552-31
• Status: Recruiting
• Phase: Phase 2
• Start date: July 25, 2023
• Est. completion date: November 9, 2026

Study information

• Verified date: April 2024
• Source: Biogen
• Contact: US Biogen Clinical Trial Center
• Phone: 866-633-4636
• Email: clinicaltrials[@]biogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 275
• Est. completion date: November 9, 2026
• Est. primary completion date: July 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Forms of Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• BIIB091
Administered as specified in the treatment arm.
• DRF
Administered as specified in the treatment arm.
• Placebo
Administered as specified in the treatment arm.

Locations

Country	Name	City	State
Bulgaria	'MHAT Avis - Medica' OOD	Pleven
Bulgaria	UMHAT 'Dr. Georgi Stranski', EAD	Pleven
Bulgaria	UMHAT 'Sv. Georgi', EAD	Plovdiv
Bulgaria	Acibadem City Clinic Tokuda University Hospital Ead	Sofia
Bulgaria	DCC Neoclinic EAD	Sofia
Bulgaria	Diagnostic Consultation Center CONVEX EOOD	Sofia
Bulgaria	MHATNP 'Sv.Naum', EAD	Sofia
Bulgaria	UMHAT "Sv. Ivan Rilski", EAD	Sofia
Bulgaria	University First MHAT-Sofia, 'St. Joan Krastitel' EAD	Sofia
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Nemocnice Jihlava p.o.	Jihlava
Czechia	Fakultni Thomayerova nemocnice	Praha 4-Krc
Czechia	Krajska zdravotni a.s. - Nemocnice Teplice o.z.	Teplice
Germany	Klinikum Bayreuth GmbH- Hohe Warte	Bayreuth	Bayern
Germany	Studienzentrum fur Neurologie und Psychiatrie	Boeblingen	Baden Wuerttemberg
Germany	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden
Germany	Universitaetsklinikum Duesseldorf AoeR	Duesseldorf	Nordrhein Westfalen
Germany	ZNS - Zentrum fuer Neurologisch-Psychiatrische Studien	Siegen	Nordrhein Westfalen
Germany	Neuropraxis Muenchen Sued	Unterhaching	Bayern
Italy	Fondazione Istituto G.Giglio di Cefalù	Cefalù	Palermo
Italy	IRCCS Ospedale Policlinico San Martino	Genova
Italy	Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"	Napoli
Italy	Fondazione Istituto Neurologico Casimiro Mondino	Pavia
Italy	I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo	Pozzilli	Isernia
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Roma
Italy	Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza	Roma
Poland	COPERNICUS Podmiot Leczniczy Sp. z o. o.,	Gdansk
Poland	Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. Jana Pawla II	Grodzisk Mazowiecki
Poland	Centrum Medyczne Pratia Katowice	Katowice
Poland	M.A. - LEK A.M.Maciejowscy SC.	Katowice
Poland	Nzoz Novo-Med	Katowice
Poland	Resmedica Sp.z o.o	Kielce
Poland	MCD Medical	Krakow
Poland	Szpital Uniwersytecki w Krakowie	Krakow
Poland	Centrum Neurologii K. Selmaj	Lodz
Poland	Instytut Zdrowia dr Boczarska-Jedynak sp.z.o.o, Sp.K	Oswiecim
Poland	Med-Polonia Sp. z o.o.	Poznan
Poland	NZOZ 'NEURO-KARD', 'Ilkowski i Partnerzy' Sp. Partn. Lek.	Poznan
Poland	Nzoz Palomed	Rzeszów
Poland	NeuroProtect Sp. z o.o.	Warszawa
Poland	Wielospecjalistyczne Centrum Medyczne Ibismed	Zabrze
Puerto Rico	Caribbean Center for Clinical Research	Guaynabo
Romania	S.C Neurocity S.R.L	Bucure?ti
Romania	Spitalul Universitar de Urgenta Elias	Bucuresti
Romania	S.C Clubul Sanatatii SRL	Campulung Muscel
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital Universitario Virgen de la Arrixaca	El Palmar	Murcia
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon	Madrid
Switzerland	Inselspital - Universitaetsspital Bern	Bern
Switzerland	Ospedale Regionale di Lugano	Lugano	Ticino
Switzerland	Universitaetsspital Zuerich	Zuerich
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Colorado School of Medic	Aurora	Colorado
United States	Alta Bates Summit Medical Center	Berkeley	California
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	The Boster Center for Multiple Sclerosis	Columbus	Ohio
United States	Neurology Clinic, PC	Cordova	Tennessee
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	International Neurorehabilitation Institute	Lutherville	Maryland
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	South Shore Neurologic Associates, P.C.	Patchogue	New York
United States	Washington University	Saint Louis	Missouri
United States	The University of Texas Health Science Center San Antonio	San Antonio	Texas
United States	HonorHealth Neurology	Scottsdale	Arizona
United States	Vero Beach Neurology and Research Institute	Vero Beach	Florida
United States	Wake Forest University - School of Medicine - Central	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Germany,  Italy,  Poland,  Puerto Rico,  Romania,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Part 2: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions		Week 8 to Week 16
Secondary	Part 1: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions		Week 8 to Week 16
Secondary	Part 1: Cumulative Number of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Secondary	Part 1: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Secondary	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
Secondary	Part 1: Number of Participants With Change From Baseline in Heart Rate		Up to Week 50
Secondary	Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities		Up to Week 50
Secondary	Part 2: Cumulative Number of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Secondary	Part 2: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions		Week 8 to Week 16
Secondary	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
Secondary	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
Secondary	Part 2: Number of Participants With Change From Baseline in QTcF, RR, PR, QRS, and QT intervals		Up to Week 50
Secondary	Part 2: Number of Participants With Change From Baseline in Heart Rate		Up to Week 50
Secondary	Part 2: Number of Participants With ECG Abnormalities as Assessed by 12-Lead ECG Measurements		Up to Week 50