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

Relapsing Forms of Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05083923
• Other study ID #: 272MS303
• Status: Recruiting
• Phase: Phase 3
• Start date: November 18, 2021
• Est. completion date: July 15, 2024

Study information

• Verified date: October 2023
• Source: Biogen
• Contact: US Biogen Clinical Trial Center
• Phone: 866-633-4636
• Email: clinicaltrials[@]biogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 15, 2024
• Est. primary completion date: July 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Forms of Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Diroximel fumarate
Administered as specified in the treatment arm

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing	Beijing
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Xiangya Hospital, Central South University	Changsha	Hunan
China	Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	Dongguan People's Hospital	Dongguan	Guangdong
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The Third Affiliated Hospital, Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The Second Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The First Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	The Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia
China	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch	Shanghai	Shanghai
China	Shengjing Hospital of China Medical University	Shengyang	Liaoning
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Shanxi Provincial People's Hospital	Taiyuan	Shanxi
China	Tangshan Gongren Hospital	Tangshan	Hebei
China	Tianjin Medical University Affiliated General Hospital	Tianjin	Tianjin
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology	Wuhan	Hubei
China	Tangdu Hospital, Fourth Military Medical University	Xi'an	Shanxi
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
Japan	NHO Asahikawa Medical Center	Asahikawa-shi	Hokkaido
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo-To
Japan	Chiba University Hospital	Chiba-shi	Chiba-Ken
Japan	Fukuoka University Hospital	Fukuoka-shi	Fukuoka-Ken
Japan	Saitama Medical Center	Kawagoe-shi	Saitama-Ken
Japan	Hospital of the University of Occupational and Environmental Health	Kitakyushu-shi	Fukuoka-Ken
Japan	National Center of Neurology and Psychiatry	Kodaira-shi	Tokyo-To
Japan	Southern Tohoku Medical Clinic	Koriyama-shi	Fukushima-Ken
Japan	Kansai Medical University Medical Center	Moriguchi-shi	Osaka-Fu
Japan	Iwate Medical University Uchimaru Medical Center	Morioka-shi	Iwate-Ken
Japan	Niigata University Medical & Dental Hospital	Niigata-shi	Niigata-Ken
Japan	Obihiro Kosei Hospital	Obihiro-City	Hokkaido
Japan	Ebara Hospital	Ota-ku	Tokyo-To
Japan	NHO Hokkaido Medical Center	Sapporo-shi	Hokkaido
Japan	Tohoku Medical and Pharmaceutical University Hospital	Sendai City	Miyagi-Ken
Japan	Tohoku University Hospital	Sendai City	Miyagi-Ken
Japan	Department of Neurosurgery, Tokyo Women's Medical University	Shinjuku-ku	Tokyo-To
Japan	Ehime University Hospital	Toon-shi	Ehime-Ken
Japan	University of Tsukuba Hospital	Tsukuba-shi	Ibaraki-Ken
Japan	Yamaguchi University Hospital	Ube-shi	Yamaguchi-Ken
Japan	Wakayama Medical University Hospital	Wakayama-shi	Wakayama-Ken
Japan	Tokyo Womens Medical University Yachiyo Medical Center	Yachiyo-City	Chiba-Ken
Japan	Yokohama City University Hospital	Yokohama-shi	Kanagawa-Ken

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

China,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Part 1: Number of Participants with PCS Change from Baseline in 12-Lead Electrocardiogram (ECG) Parameters		Baseline (Day 1) to Week 24
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Part 2: Number of Participants with PCS Change from Baseline in 12-Lead ECG Parameters		Baseline (Day 1) to Week 48
Primary	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
Primary	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	Part 1: Plasma Concentrations of MMF and HES		Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1: Elimination Half-Life (t½) of MMF		Predose and at multiple timepoints postdose on Days 29, 57, 85, 113, 141 and 169