Clinical trial NCT05083923: A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing Forms of Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2021-10-19
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Week 24
measure: Part 1: Number of Participants with Potentially Clinically Serious (PCS) Change from Baseline in Clinical Laboratory Parameters
timeFrame: Baseline (Day 1) to Week 24
measure: Part 1: Number of Participants with PCS Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters
timeFrame: Baseline (Day 1) to Week 24
measure: Part 1: Number of Participants with PCS Change from Baseline in Vital Sign Parameters
timeFrame: Baseline (Day 1) to Week 24
measure: Part 1: Number of Participants with Columbia Suicide Severity Rating Scale (C-SSRS) Events
timeFrame: Baseline (Day 1) to Week 24
measure: Part 2: Number of Participants with AEs and SAEs
timeFrame: Up to Week 48
measure: Part 2: Number of Participants with PCS Change from Baseline in Clinical Laboratory Parameters
timeFrame: Baseline (Day 1) to Week 48
measure: Part 2: Number of Participants with PCS Change from Baseline in 12-Lead ECG Parameters
timeFrame: Baseline (Day 1) to Week 48
measure: Part 2: Number of Participants with PCS Change from Baseline in Vital Sign Parameters
timeFrame: Baseline (Day 1) to Week 48
measure: Part 2: Number of Participants with C-SSRS Events
timeFrame: Baseline (Day 1) to Week 48
Secondary outcomes:
measure: Part 1: Plasma Concentrations of MMF and HES
timeFrame: Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169
measure: Part 1: Maximum Observed Concentration (Cmax) of MMF and HES
timeFrame: Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169
measure: Part 1: Area Under the Concentration-Time Curve from Time Zero to Time of Last Measurable Concentration (AUClast) of MMF and HES
timeFrame: Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169
measure: Part 1: Time to Reach Cmax (Tmax) of MMF and HES
timeFrame: Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169
measure: Part 1: Elimination Half-Life (t½) of MMF
timeFrame: Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
state: Gansu
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou First People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Tangshan
country: China
facility: Tangshan Gongren Hospital
state: Hebei
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Provincial People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shengyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Xi'an
country: China
facility: Tangdu Hospital, Fourth Military Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Affiliated General Hospital
state: Tianjin
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Chiba-shi
country: Japan
facility: Chiba University Hospital
state: Chiba-Ken
city: Yachiyo-City
country: Japan
facility: Tokyo Womens Medical University Yachiyo Medical Center
state: Chiba-Ken
city: Toon-shi
country: Japan
facility: Ehime University Hospital
state: Ehime-Ken
city: Fukuoka-shi
country: Japan
facility: Fukuoka University Hospital
state: Fukuoka-Ken
city: Kitakyushu-shi
country: Japan
facility: Hospital of the University of Occupational and Environmental Health
state: Fukuoka-Ken
city: Koriyama-shi
country: Japan
facility: Southern Tohoku Medical Clinic
state: Fukushima-Ken
city: Asahikawa-shi
country: Japan
facility: NHO Asahikawa Medical Center
state: Hokkaido
city: Obihiro-City
country: Japan
facility: Obihiro Kosei Hospital
state: Hokkaido
city: Sapporo-shi
country: Japan
facility: NHO Hokkaido Medical Center
state: Hokkaido
city: Tsukuba-shi
country: Japan
facility: University of Tsukuba Hospital
state: Ibaraki-Ken
city: Morioka-shi
country: Japan
facility: Iwate Medical University Uchimaru Medical Center
state: Iwate-Ken
city: Yokohama-shi
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa-Ken
city: Sendai City
country: Japan
facility: Tohoku University Hospital
state: Miyagi-Ken
city: Sendai City
country: Japan
facility: Tohoku Medical and Pharmaceutical University Hospital
state: Miyagi-Ken
city: Niigata-shi
country: Japan
facility: Niigata University Medical & Dental Hospital
state: Niigata-Ken
city: Moriguchi-shi
country: Japan
facility: Kansai Medical University Medical Center
state: Osaka-Fu
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center
state: Saitama-Ken
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
state: Tokyo-To
city: Kodaira-shi
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo-To
city: Ota-ku
country: Japan
facility: Ebara Hospital
state: Tokyo-To
city: Shinjuku-ku
country: Japan
facility: Department of Neurosurgery, Tokyo Women's Medical University
state: Tokyo-To
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama-Ken
city: Ube-shi
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi-Ken
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: