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

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

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).

Study Overview

• Status: Completed
• Conditions: Relapsing Forms of Multiple Sclerosis
• Intervention / Treatment: Drug: Diroximel fumarate

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100006
      • Beijing Hospital
    • Beijing, Beijing Municipality, China, 100050
      • Beijing Tiantan Hospital, Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730030
      • Lanzhou University Second Hospital
  • Guangdong
    • Dongguan, Guangdong, China, 523059
      • Dongguan People's Hospital
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510260
      • The second Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
  • Hebei
    • Tangshan, Hebei, China, 063003
      • Tangshan Gongren Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150086
      • The Second Affiliated Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China, 150040
      • The First Affiliated Hospital of Harbin Medical University
  • Hu'nan
    • Changsha, Hu'nan, China, 410008
      • Xiangya Hospital, Central South University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China, 10050
      • The Affiliated Hospital of Inner Mongolia Medical University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215004
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shengyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Ningxia Hui
    • Yinchuan, Ningxia Hui, China, 750004
      • General Hospital of Ningxia Medical University
  • Shan'xi
    • Xi'an, Shan'xi, China, 710038
      • Tangdu Hospital, Fourth Military Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200001
      • Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch
  • Shanxi
    • Taiyuan, Shanxi, China, 30012
      • Shanxi Provincial People's Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300052
      • Tianjin Medical University Affiliated General Hospital
  • Yun'nan
    • Kunming, Yun'nan, China, 650032
      • First Affiliated Hospital of Kunming Medical University
• Japan
  • Chiba
    • Chiba, Chiba, Japan, 260-8677
      • Chiba University Hospital
    • Yachiyo, Chiba, Japan, 276-8524
      • Tokyo Womens Medical University Yachiyo Medical Center
  • Ehime
    • Toon-shi, Ehime, Japan, 791-0295
      • Ehime University Hospital
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 814-0180
      • Fukuoka University Hospital
    • Kitakyushu-shi, Fukuoka, Japan, 807-8556
      • Hospital of the University of Occupational and Environmental Health
  • Fukushima
    • Koriyama-shi, Fukushima, Japan, 963-8563
      • Southern TOHOKU Medical Clinic
  • Hokkaido
    • Asahikawa-shi, Hokkaido, Japan, 070-8644
      • NHO Asahikawa Medical Center
    • Obihiro, Hokkaido, Japan, 080-0024
      • Obihiro Kosei Hospital
    • Sapporo, Hokkaido, Japan, 063-0005
      • NHO Hokkaido Medical Center
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
      • University of Tsukuba Hospital
  • Iwate
    • Morioka, Iwate, Japan, 020-8505
      • Iwate Medical University Uchimaru Medical Center
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital
  • Miyagi
    • Sendai, Miyagi, Japan, 980-8574
      • Tohoku University Hospital
    • Sendai, Miyagi, Japan, 983-8512
      • Tohoku Medical and Pharmaceutical University Hospital
  • Niigata
    • Niigata, Niigata, Japan, 951-8520
      • Niigata University Medical & Dental Hospital
  • Osaka
    • Moriguchi-shi, Osaka, Japan, 570-8507
      • Kansai Medical University Medical Center
  • Saitama
    • Kawagoe-shi, Saitama, Japan, 350-8550
      • Saitama Medical Center
  • Tokyo-To
    • Bunkyō City, Tokyo-To, Japan, 113-8431
      • Juntendo University Hospital
    • Kodaira-shi, Tokyo-To, Japan, 187-8551
      • National Center of Neurology and Psychiatry
    • Shinjuku-ku, Tokyo-To, Japan, 162-8666
      • Department of Neurosurgery, Tokyo Women's Medical University
    • Ōta-ku, Tokyo-To, Japan, 145-0065
      • Ebara Hospital
  • Wakayama
    • Wakayama, Wakayama, Japan, 641-8510
      • Wakayama Medical University Hospital
  • Yamaguchi
    • Ube-shi, Yamaguchi, Japan, 755-8505
      • Yamaguchi University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diroximel Fumarate (DRF); 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; Administered as specified in the treatment arm; Other Names: BIIB098; Vumerity; ALK8700

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether/not related to the medicinal (investigational) product. An AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment, or completion of the safety follow-up visit, if applicable.(i.e. for participants who prematurely discontinued study treatment or withdrew from the study) . An SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs.	Baseline (Day 1) up to Week 24 (for prematurely discontinued participants, AEs were reported up to 2 weeks post discontinuation)
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters	Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine.	Baseline (Day 1) to Week 24
Part 1: Number of Participants With Abnormal Shift in 12-Lead Electrocardiogram (ECG) Values	The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal.	Baseline (Day 1) to Week 24
Part 1: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters	Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature < 36 and > 38 degrees Celsius (C), pulse rate < 60 and > 100 beats per minute (bpm), systolic blood pressure (< 90, > 140 and > 160 millimeters of mercury [mmHg]), diastolic blood pressure < 50, > 90 and > 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate < 12 and > 20 breaths per minute.	Baseline (Day 1) to Week 24
Part 1: Number of Participants With Columbia Suicide Severity Rating Scale (C-SSRS) Events	The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and non-suicidal self-injurious behavior.	Baseline (Day 1) to Week 24
Parts 1 and 2: Number of Participants With TEAEs and TESAEs	An AE was any unfavorable and unintended sign, symptom, or disease temporally associated with use of medicinal (investigational) product, whether/not related to medicinal (investigational) product. AE was considered treatment-emergent if it starts or worsens on or after the date of the first dose of study drug in the study until 1 day after the last dose of treatment. SAE is any untoward medical occurrence that at any dose results in death, is a life-threatening event, requires inpatient hospitalization or prolongation of existing hospitalization, results in a significant disability/incapacity or congenital anomaly, is a medically important event. TEAEs included both serious and non-serious TEAEs. TEAEs and TESAEs for participants were collected cumulatively for Parts 1 and 2.	From Day 1 up to the end of the study (up to Week 50)
Part 2: Number of Participants With Potentially Clinically Significant Abnormalities in Laboratory Parameters	Laboratory assessments included hematology, blood chemistry, and urinalysis parameters. Hematology parameters:basophils, hematocrit, red blood cell, total and differential leukocytes, platelets, lymphocytes, monocytes, neutrophils, eosinophils, hemoglobin. Blood chemistry parameters:sodium, potassium, chloride, glucose, calcium, uric acid, total protein, albumin, creatine phosphokinase, Lipid profile: blood cholesterol,high-density lipoprotein,low-density lipoprotein, and triglycerides,serum follicle-stimulating hormone,Vitamin D,thyroid stimulating hormone,serum pregnancy, HIV/Hepatitis screen,tuberculosis test,alanine aminotransferase,aspartate aminotransferase,Lactate Dehydrogenase,alkaline phosphatase,gamma glutamyl transferase,total bilirubin,blood urea nitrogen,creatinine and bicarbonate. Urinalysis parameters:color,pH,specific gravity,ketones,protein,glucose, bilirubin,nitrite,urobilinogen,occult blood,microscopic examination,urine albumin,beta-2-microglobulin,urine creatinine.	Baseline (Day 1) to Week 48
Part 2: Number of Participants With Abnormal Shift in 12-Lead ECG Values	The number of participants with shifts to categorical values of ECG interpretation (e.g. abnormal) were presented by each cohort. Abnormal shift includes a shift from normal or unknown to abnormal.	Baseline (Day 1) to Week 48
Part 2: Number of Participants With Clinically Relevant Abnormalities in Vital Sign Parameters	Vital sign assessment included temperature, pulse rate systolic blood pressure, diastolic blood pressure, and respiratory rate. The criteria for determining potentially clinically relevant abnormalities in vital signs included: temperature < 36 and > 38 degrees C, pulse rate < 60 and > 100 bpm, systolic blood pressure (< 90, > 140 and > 160 mmHg), diastolic blood pressure < 50, > 90 and > 100 mmHg, weight (7% or more increase from baseline, 7% or more decrease from baseline) and respiratory rate < 12 and > 20 breaths per minute.	Baseline (Day 1) to Week 48
Part 2: Number of Participants With C-SSRS Events	The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation, suicidal behavior and non-suicidal self-injurious behavior. The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal behavior (preparatory acts or behavior, aborted attempt, interrupted attempt, Suicidal behavior, completed suicide), suicidal ideation (wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods, active suicidal ideation with some intent, active suicidal ideation with specific plan and intent) and 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 Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set	Summarized data for plasma concentration of MMF at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Plasma Concentration of 2-Hydroxyethyl Succinimide (HES)-Intensive PK Analysis Set	Summarized data for plasma concentration of HES at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Plasma Concentrations of MMF-Sparse PK Analysis Set		Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57
Part 1: Plasma Concentrations of HES-Sparse PK Analysis Set		Pre-dose and 2 to 3 hours post-dose on Day 29 and Day 57
Part 1: Maximum Observed Concentration (Cmax) of MMF-Intensive PK Analysis Set	Summarized data for Cmax at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Cmax of HES-Intensive PK Analysis Set	Summarized data for Cmax at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of MMF-Intensive PK Analysis Set	Summarized data for AUClast at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: AUClast of HES-Intensive PK Analysis Set	Summarized data for AUClast at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Time to Reach Cmax (Tmax) of MMF-Intensive PK Analysis Set	Summarized data for Tmax at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Tmax of HES-Intensive PK Analysis Set	Summarized data for Tmax at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169
Part 1: Elimination Half-Life (t½) of MMF-Intensive PK Analysis Set	Summarized data for t½ at all timepoints is reported.	Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2021
• Primary Completion (Actual): September 11, 2024
• Study Completion (Actual): September 11, 2024

Study Registration Dates

• First Submitted: October 6, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Estimated): October 24, 2025
• Last Update Submitted That Met QC Criteria: October 10, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; diroximel fumarate
• Other Study ID Numbers: 272MS303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes