A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS)
- Conditions
- Relapsing Forms of Multiple Sclerosis
- Interventions
- Registration Number
- NCT05083923
- Lead Sponsor
- Biogen
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Diroximel Fumarate (DRF) Diroximel fumarate 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.
- Primary Outcome Measures
Name Time Method Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Week 24 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.
Part 1: Number of Participants with PCS Change from Baseline in Vital Sign Parameters Baseline (Day 1) to Week 24 Vital sign parameters will include temperature, pulse rate, systolic and diastolic blood pressure, and respiratory rate.
Part 1: Number of Participants with Columbia Suicide Severity Rating Scale (C-SSRS) Events Baseline (Day 1) to Week 24 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").
Part 2: Number of Participants with PCS Change from Baseline in Clinical Laboratory Parameters Baseline (Day 1) to Week 48 Clinical laboratory parameters will include chemistry, hematology and urinalysis parameters.
Part 2: Number of Participants with C-SSRS Events Baseline (Day 1) to Week 48 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").
Part 1: Number of Participants with Potentially Clinically Serious (PCS) Change from Baseline in Clinical Laboratory Parameters Baseline (Day 1) to Week 24 Clinical laboratory parameters will include chemistry, hematology and urinalysis parameters.
Part 2: Number of Participants with AEs and SAEs Up to Week 48 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.
Part 2: Number of Participants with PCS Change from Baseline in 12-Lead ECG Parameters Baseline (Day 1) to Week 48 Part 1: Number of Participants with PCS Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters Baseline (Day 1) to Week 24 Part 2: Number of Participants with PCS Change from Baseline in Vital Sign Parameters Baseline (Day 1) to Week 48 Vital sign parameters will include temperature, pulse rate, systolic and diastolic blood pressure, and respiratory rate.
- Secondary Outcome Measures
Name Time Method 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 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
Trial Locations
- Locations (52)
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Beijing Tiantan Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Lanzhou University Second Hospital
🇨🇳Lanzhou, Gansu, China
Dongguan People's Hospital
🇨🇳Dongguan, Guangdong, China
The First Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Guangzhou First People's Hospital
🇨🇳Guangzhou, Guangdong, China
The Second Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The Third Affiliated Hospital, Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Tangshan Gongren Hospital
🇨🇳Tangshan, Hebei, China
The First Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The Second Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
🇨🇳Wuhan, Hubei, China
Xiangya Hospital, Central South University
🇨🇳Changsha, Hunan, China
The Affiliated Hospital of Inner Mongolia Medical University
🇨🇳Hohhot, Inner Mongolia, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Jiangxi Provincial People's Hospital
🇨🇳Nanchang, Jiangxi, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Shengjing Hospital of China Medical University
🇨🇳Shengyang, Liaoning, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch
🇨🇳Shanghai, Shanghai, China
Shanxi Provincial People's Hospital
🇨🇳Taiyuan, Shanxi, China
Tangdu Hospital, Fourth Military Medical University
🇨🇳Xi'an, Shanxi, China
Sichuan Provincial People's Hospital
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University Affiliated General Hospital
🇨🇳Tianjin, Tianjin, China
First Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
Chiba University Hospital
🇯🇵Chiba-shi, Chiba-Ken, Japan
Tokyo Womens Medical University Yachiyo Medical Center
🇯🇵Yachiyo-City, Chiba-Ken, Japan
Ehime University Hospital
🇯🇵Toon-shi, Ehime-Ken, Japan
Fukuoka University Hospital
🇯🇵Fukuoka-shi, Fukuoka-Ken, Japan
Hospital of the University of Occupational and Environmental Health
🇯🇵Kitakyushu-shi, Fukuoka-Ken, Japan
Southern Tohoku Medical Clinic
🇯🇵Koriyama-shi, Fukushima-Ken, Japan
NHO Asahikawa Medical Center
🇯🇵Asahikawa-shi, Hokkaido, Japan
Obihiro Kosei Hospital
🇯🇵Obihiro-City, Hokkaido, Japan
NHO Hokkaido Medical Center
🇯🇵Sapporo-shi, Hokkaido, Japan
University of Tsukuba Hospital
🇯🇵Tsukuba-shi, Ibaraki-Ken, Japan
Iwate Medical University Uchimaru Medical Center
🇯🇵Morioka-shi, Iwate-Ken, Japan
Yokohama City University Hospital
🇯🇵Yokohama-shi, Kanagawa-Ken, Japan
Tohoku University Hospital
🇯🇵Sendai City, Miyagi-Ken, Japan
Tohoku Medical and Pharmaceutical University Hospital
🇯🇵Sendai City, Miyagi-Ken, Japan
Niigata University Medical & Dental Hospital
🇯🇵Niigata-shi, Niigata-Ken, Japan
Kansai Medical University Medical Center
🇯🇵Moriguchi-shi, Osaka-Fu, Japan
Saitama Medical Center
🇯🇵Kawagoe-shi, Saitama-Ken, Japan
Juntendo University Hospital
🇯🇵Bunkyo-ku, Tokyo-To, Japan
National Center of Neurology and Psychiatry
🇯🇵Kodaira-shi, Tokyo-To, Japan
Ebara Hospital
🇯🇵Ota-ku, Tokyo-To, Japan
Department of Neurosurgery, Tokyo Women's Medical University
🇯🇵Shinjuku-ku, Tokyo-To, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama-shi, Wakayama-Ken, Japan
Yamaguchi University Hospital
🇯🇵Ube-shi, Yamaguchi-Ken, Japan