Clinical trial NCT05798520: 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)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Relapsing Forms of Multiple Sclerosis
Keywords: Multiple Sclerosis
Diroximel fumarate
BIIB091
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2023-04-04
Enrollment: 275
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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 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.

Primary outcomes:
measure: Part 1: Number of Participants With Adverse Events (AEs)
timeFrame: Day 1 up to Week 50
measure: Part 1: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From signing the informed consent form (ICF) to Week 50
measure: Part 2: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions
timeFrame: Week 8 to Week 16
Secondary outcomes:
measure: Part 1: Cumulative Number of New T1 Gadolinium-Enhancing (GdE) Lesions
timeFrame: Week 8 to Week 16
measure: Part 1: Cumulative Number of New or Enlarging T2 Hyperintense Lesions
timeFrame: Week 8 to Week 16
measure: Part 1: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions
timeFrame: Week 8 to Week 16
measure: Part 1: Mean Change From Baseline in QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF), RR, PR, QRS, and QT Intervals
timeFrame: Up to Week 50
measure: Part 1: Number of Participants With Change From Baseline in Heart Rate
timeFrame: Up to Week 50
measure: Part 1: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
timeFrame: Up to Week 50
measure: Part 2: Cumulative Number of New or Enlarging T2 Hyperintense Lesions
timeFrame: Week 8 to Week 16
measure: Part 2: Cumulative Volume of New or Enlarging T2 Hyperintense Lesions
timeFrame: Week 8 to Week 16
measure: Part 2: Number of Participants With AEs
timeFrame: Day 1 up to Week 50
measure: Part 2: Number of Participants With SAEs
timeFrame: From signing of ICF up to Week 50
measure: Part 2: Number of Participants With Change From Baseline in QTcF, RR, PR, QRS, and QT intervals
timeFrame: Up to Week 50
measure: Part 2: Number of Participants With Change From Baseline in Heart Rate
timeFrame: Up to Week 50
measure: Part 2: Number of Participants With ECG Abnormalities as Assessed by 12-Lead ECG Measurements
timeFrame: Up to Week 50
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Neurology
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Medical Center
state: California
city: Orange
country: United States
facility: University of California at Irvine Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medic
state: Colorado
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Vero Beach
country: United States
facility: Vero Beach Neurology and Research Institute
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Lutherville
country: United States
facility: International Neurorehabilitation Institute
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Teaneck
country: United States
facility: Holy Name
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Patchogue
country: United States
facility: South Shore Neurologic Associates, P.C.
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University - School of Medicine - Central
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Company
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: The Boster Center for Multiple Sclerosis
state: Ohio
city: Cordova
country: United States
facility: Neurology Clinic, PC
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt MS Center
state: Tennessee
city: San Antonio
country: United States
facility: The University of Texas Health Science Center San Antonio
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin
state: Wisconsin
city: Pleven
country: Bulgaria
facility: 'MHAT Avis - Medica' OOD
city: Pleven
country: Bulgaria
facility: UMHAT 'Dr. Georgi Stranski', EAD
city: Plovdiv
country: Bulgaria
facility: UMHAT 'Sv. Georgi', EAD
city: Sofia
country: Bulgaria
facility: MHATNP 'Sv.Naum', EAD
city: Sofia
country: Bulgaria
facility: University First MHAT-Sofia, 'St. Joan Krastitel' EAD
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Tokuda University Hospital Ead
city: Sofia
country: Bulgaria
facility: DCC Neoclinic EAD
city: Sofia
country: Bulgaria
facility: UMHAT "Sv. Ivan Rilski", EAD
city: Sofia
country: Bulgaria
facility: Diagnostic Consultation Center CONVEX EOOD
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny v Brne
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava p.o.
city: Praha 4-Krc
country: Czechia
facility: Fakultni Thomayerova nemocnice
city: Teplice
country: Czechia
facility: Krajska zdravotni a.s. - Nemocnice Teplice o.z.
city: Boeblingen
country: Germany
facility: Studienzentrum fur Neurologie und Psychiatrie
state: Baden Wuerttemberg
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth GmbH- Hohe Warte
state: Bayern
city: Unterhaching
country: Germany
facility: Neuropraxis Muenchen Sued
state: Bayern
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf AoeR
state: Nordrhein Westfalen
city: Siegen
country: Germany
facility: ZNS - Zentrum fuer Neurologisch-Psychiatrische Studien
state: Nordrhein Westfalen
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Pozzilli
country: Italy
facility: I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
state: Isernia
city: Cefalù
country: Italy
facility: Fondazione Istituto G.Giglio di Cefalù
state: Palermo
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"
city: Pavia
country: Italy
facility: Fondazione Istituto Neurologico Casimiro Mondino
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Umberto I - Università di Roma La Sapienza
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o. o.,
city: Grodzisk Mazowiecki
country: Poland
facility: Samodzielny Publiczny Specjalistyczny Szpital Zachodni im. Jana Pawla II
city: Katowice
country: Poland
facility: Centrum Medyczne Pratia Katowice
city: Katowice
country: Poland
facility: M.A. - LEK A.M.Maciejowscy SC.
city: Katowice
country: Poland
facility: Nzoz Novo-Med
city: Kielce
country: Poland
facility: Resmedica Sp.z o.o
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Lodz
country: Poland
facility: Centrum Neurologii K. Selmaj
city: Oswiecim
country: Poland
facility: Instytut Zdrowia dr Boczarska-Jedynak sp.z.o.o, Sp.K
city: Poznan
country: Poland
facility: Med-Polonia Sp. z o.o.
city: Poznan
country: Poland
facility: NZOZ 'NEURO-KARD', 'Ilkowski i Partnerzy' Sp. Partn. Lek.
city: Rzeszów
country: Poland
facility: Nzoz Palomed
city: Warszawa
country: Poland
facility: NeuroProtect Sp. z o.o.
city: Zabrze
country: Poland
facility: Wielospecjalistyczne Centrum Medyczne Ibismed
city: Guaynabo
country: Puerto Rico
facility: Caribbean Center for Clinical Research
city: Bucuresti
country: Romania
facility: Spitalul Universitar de Urgenta Elias
city: București
country: Romania
facility: S.C Neurocity S.R.L
city: Campulung Muscel
country: Romania
facility: S.C Clubul Sanatatii SRL
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Madrid
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
state: Murcia
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
state: Ticino
city: Bern
country: Switzerland
facility: Inselspital - Universitaetsspital Bern
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: