A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS)

Study Overview
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Brief Summary
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The primary objectives of this study are to determine the safety and tolerability of DRF administered for up to 24 weeks in adult East Asian participants with RMS (Part 1) and to determine the safety and tolerability of DRF administered for up to 48 weeks in adult East Asian participants with RMS (Part 2). The secondary objective of this study is to evaluate the pharmacokinetic(s) (PK) of DRF metabolites (monomethyl fumarate [MMF] and 2-hydroxyethyl succinimide [HES]) following multiple doses of DRF in a subset of adult East Asian participants with RMS (Part 1).

Official Title
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An Open-Label, Single-Arm, Multicenter, Phase 3 Study to Evaluate the Safety and Tolerability, and Pharmacokinetics of Diroximel Fumarate (BIIB098) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis

Conditions
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Relapsing Forms of Multiple Sclerosis

Intervention / Treatment
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* Drug: Diroximel fumarate


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have a diagnosis of RMS, as defined by revised 2017 McDonald's criteria. Expanded Disability Status Scale (EDSS) score between 0.0 and 5.0, inclusive, at screening and baseline visit (Day 1). Neurologically stable with no evidence of relapse within 30 days prior to baseline visit (Day 1). For Japanese participants: Born in Japan and biological parents and grandparents were of Japanese origin. If previously lived outside of Japan for more than 5 years, must not have had a significantly modified diet since leaving Japan. For Chinese participants: Born in China, and biological parents and grandparents were of Chinese origin. If previously lived outside of China for more than 5 years, must not have had a significantly modified diet since leaving China. Key Exclusion Criteria: Has a multiple sclerosis (MS) relapse that has occurred within the 30 days prior to randomization and/or the participant has not stabilized from a previous relapse prior to randomization. History of severe allergic or anaphylactic reactions or of any allergic reactions that, in the opinion of the investigator, are likely to be exacerbated by any component of the study treatment. History of, or ongoing, malignant disease, including solid tumors and hematologic malignancies. Has a history of gastrointestinal (GI) surgery (except appendectomy or cholecystectomy that occurred more than 6 months prior to screening), irritable bowel syndrome, inflammatory bowel disease (Crohn's disease, ulcerative colitis), or other clinically significant and active GI condition per the investigator's discretion. History of clinically significant recurring or active GI symptoms (e.g., nausea, diarrhea, dyspepsia, constipation) within 90 days of screening, including symptoms that require the initiation of symptomatic medical treatment (e.g., initiation of a medication to treat gastroesophageal reflux disease) or a change in symptomatic medical treatment (e.g., an increase in dose) within 90 days prior to screening. History of systemic hypersensitivity reaction to DRF, dimethyl fumarate (DMF), MMF or other fumaric esters, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study. Evidence of current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 14 days prior to Screening, between screening and baseline visit (Day 1), or at baseline visit (Day 1), including but not limited to a fever (temperature >37.5 degrees Celsius [°C]), new and persistent cough, breathlessness, or loss of taste and/or smell. Evidence of current SARS-CoV-2 infection within 14 days prior to Screening or during Screening, will be eligible for rescreening, provided that the participant is asymptomatic for 14 days prior to rescreening. Have close contact within 14 days prior to Day 1 with individual(s) with suspected SARS-CoV-2 infection. For participants who had close contact with individual(s) with suspected SARS-CoV-2 infection within 14 days prior to Day 1, as determined by the Investigator, will be eligible for rescreening, provided that the participant is asymptomatic for 14 days after the contact. History or positive test result at screening for human immunodeficiency virus (HIV). Previous participation in this study or previous studies with DRF, DMF, or MMF. Has a clinically significant history of suicidal ideation or suicidal behavior occurring in the past 12 months as assessed by the C-SSRS at Screening. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diroximel Fumarate (DRF)<br>Japanese and Chinese participants will initiate treatment with DRF 231 milligrams (mg), oral capsule, twice daily on Day 1 through Day 7, followed by DRF 462 mg, oral capsules, twice daily from Day 8 up to Week 48. | Drug: Diroximel fumarate<br>* Administered as specified in the treatment arm<br>* Other names: ALK8700;|

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) and Serious Adverse Events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a 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, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An 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. | Week 24 | 
| Part 1: Number of Participants with Potentially Clinically Serious (PCS) Change from Baseline in Clinical Laboratory Parameters | Clinical laboratory parameters will include chemistry, hematology and urinalysis parameters. | Baseline (Day 1) to Week 24 | 
| Part 1: Number of Participants with PCS Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters |  | Baseline (Day 1) to Week 24 | 
| Part 1: Number of Participants with PCS Change from Baseline in Vital Sign Parameters | Vital sign parameters will include temperature, pulse rate, systolic and diastolic blood pressure, and respiratory rate. | Baseline (Day 1) to Week 24 | 
| Part 1: Number of Participants with Columbia Suicide Severity Rating Scale (C-SSRS) Events | The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assesses whether participant experiences any of the following 1. completed suicide, 2. suicide attempt (response of yes on actual attempt), 3. preparatory acts toward imminent suicidal behavior (yes on aborted attempt, interrupted attempt, preparatory acts or behavior), 4. any suicidal behavior or ideation, suicidal ideation (yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), 5. self-injurious behavior, no suicidal intent (yes on has participant engaged in non-suicidal self-injurious behavior). | Baseline (Day 1) to Week 24 | 
| Part 2: Number of Participants with AEs and SAEs | An AE is any untoward medical occurrence in a 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, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An 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. | Up to Week 48 | 
| Part 2: Number of Participants with PCS Change from Baseline in Clinical Laboratory Parameters | Clinical laboratory parameters will include chemistry, hematology and urinalysis parameters. | Baseline (Day 1) to Week 48 | 
| Part 2: Number of Participants with PCS Change from Baseline in 12-Lead ECG Parameters |  | Baseline (Day 1) to Week 48 | 
| Part 2: Number of Participants with PCS Change from Baseline in Vital Sign Parameters | Vital sign parameters will include temperature, pulse rate, systolic and diastolic blood pressure, and respiratory rate. | Baseline (Day 1) to Week 48 | 
| Part 2: Number of Participants with C-SSRS Events | The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assesses whether participant experiences any of the following 1. completed suicide, 2. suicide attempt (response of yes on actual attempt), 3. preparatory acts toward imminent suicidal behavior (yes on aborted attempt, interrupted attempt, preparatory acts or behavior), 4. any suicidal behavior or ideation, suicidal ideation (yes on wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), 5. self-injurious behavior, no suicidal intent (yes on has participant engaged in non-suicidal self-injurious behavior). | Baseline (Day 1) to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Plasma Concentrations of MMF and HES |  | Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169 | 
| Part 1: Maximum Observed Concentration (Cmax) of MMF and HES |  | Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169 | 
| Part 1: Area Under the Concentration-Time Curve from Time Zero to Time of Last Measurable Concentration (AUClast) of MMF and HES |  | Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169 | 
| Part 1: Time to Reach Cmax (Tmax) of MMF and HES |  | Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169 | 
| Part 1: Elimination Half-Life (t½) of MMF |  | Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169 |