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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Relapsing Forms of Multiple Sclerosis

Intervention / Treatment
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* Drug: BIIB091
* Drug: DRF
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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 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: 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 or positive test result at screening for human immunodeficiency virus (HIV). Current or history of hepatitis C infection regardless of viral load. Current or possible hepatitis B. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BIIB091, Multiple Sclerosis, Diroximel fumarate