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

NCT05083923 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 272MS303
• Study Type: interventional
• Target: 136
• Locations: 2 countries
• Sites: 52

Brief Summary

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).

Conditions

Relapsing Forms of Multiple Sclerosis

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (11)

• Part 1: Plasma Concentrations of Monomethyl Fumarate (MMF)-Intensive Pharmacokinetic (PK) Analysis Set

  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

  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

  Pre-dose and at 0.5,1,2,3,4,6, and 8 hours post-dose from Day 29 to Day 169

Study Arms (1)

Diroximel Fumarate (DRF)

EXPERIMENTAL

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

Interventions

Diroximel fumarate DRUG

Administered as specified in the treatment arm

Also known as: Vumerity, BIIB098, ALK8700

Diroximel Fumarate (DRF)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (52)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

Location

Beijing Hospital

Beijing, Beijing Municipality, 100006, China

Location

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100050, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

Lanzhou University Second Hospital

Lanzhou, Gansu, 730030, China

Location

Dongguan People's Hospital

Dongguan, Guangdong, 523059, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Guangzhou First People's Hospital

Guangzhou, Guangdong, 510180, China

Location

The Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510260, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

The Third Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

Location

Tangshan Gongren Hospital

Tangshan, Hebei, 063003, China

Location

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150040, China

Location

The Second Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150086, China

Location

Xiangya Hospital, Central South University

Changsha, Hu'nan, 410008, China

Location

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei, 430030, China

Location

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, 10050, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215004, China

Location

Jiangxi Provincial People's Hospital

Nanchang, Jiangxi, 330006, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Shengjing Hospital of China Medical University

Shengyang, Liaoning, 110004, China

Location

General Hospital of Ningxia Medical University

Yinchuan, Ningxia Hui, 750004, China

Location

Tangdu Hospital, Fourth Military Medical University

Xi'an, Shan'xi, 710038, China

Location

Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch

Shanghai, Shanghai Municipality, 200001, China

Location

Shanxi Provincial People's Hospital

Taiyuan, Shanxi, 30012, China

Location

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

Location

Tianjin Medical University Affiliated General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

First Affiliated Hospital of Kunming Medical University

Kunming, Yun'nan, 650032, China

Location

Chiba University Hospital

Chiba, Chiba, 260-8677, Japan

Location

Tokyo Womens Medical University Yachiyo Medical Center

Yachiyo, Chiba, 276-8524, Japan

Location

Ehime University Hospital

Toon-shi, Ehime, 791-0295, Japan

Location

Fukuoka University Hospital

Fukuoka, Fukuoka, 814-0180, Japan

Location

Hospital of the University of Occupational and Environmental Health

Kitakyushu-shi, Fukuoka, 807-8556, Japan

Location

Southern Tohoku Medical Clinic

Koriyama-shi, Fukushima, 963-8563, Japan

Location

NHO Asahikawa Medical Center

Asahikawa-shi, Hokkaido, 070-8644, Japan

Location

Obihiro Kosei Hospital

Obihiro, Hokkaido, 080-0024, Japan

Location

NHO Hokkaido Medical Center

Sapporo, Hokkaido, 063-0005, Japan

Location

University of Tsukuba Hospital

Tsukuba, Ibaraki, 305-8576, Japan

Location

Iwate Medical University Uchimaru Medical Center

Morioka, Iwate, 020-8505, Japan

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Tohoku Medical and Pharmaceutical University Hospital

Sendai, Miyagi, 983-8512, Japan

Location

Niigata University Medical & Dental Hospital

Niigata, Niigata, 951-8520, Japan

Location

Kansai Medical University Medical Center

Moriguchi-shi, Osaka, 570-8507, Japan

Location

Saitama Medical Center

Kawagoe-shi, Saitama, 350-8550, Japan

Location

Juntendo University Hospital

Bunkyō City, Tokyo-To, 113-8431, Japan

Location

National Center of Neurology and Psychiatry

Kodaira-shi, Tokyo-To, 187-8551, Japan

Location

Ebara Hospital

Ōta-ku, Tokyo-To, 145-0065, Japan

Location

Department of Neurosurgery, Tokyo Women's Medical University

Shinjuku-ku, Tokyo-To, 162-8666, Japan

Location

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510, Japan

Location

Yamaguchi University Hospital

Ube-shi, Yamaguchi, 755-8505, Japan

Location

MeSH Terms

Interventions

diroximel fumarate

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 19, 2021
• Study Start: November 18, 2021
• Primary Completion: September 11, 2024
• Study Completion: September 11, 2024
• Last Updated: October 24, 2025
• Results First Posted: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

JP (23); CN (29)