biogen/studies/attachments/NCT05083923-Synopsis.pdf

NCT05083923-Synopsis

biogen/studies/attachments/NCT05083923-LLS.pdf

NCT05083923-LLS

biogen/studies/attachments/NCT05083923-LLS_1.pdf

biogen/studies/attachments/NCT05083923-LLS_2.pdf

biogen/studies/attachments/NCT05083923-LLS_3.pdf

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).

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

Relapsing Remitting Multiple Sclerosis (RRMS)

Relapsing Multiple Sclerosis

RRMS

Multiple Sclerosis

diroximel fumarate

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

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.

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.

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.

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.

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.

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.

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.

Summarized data for plasma concentration of MMF at all timepoints is reported.

Summarized data for plasma concentration of HES at all timepoints is reported.

Summarized data for Cmax at all timepoints is reported.

Summarized data for AUClast at all timepoints is reported.

Summarized data for Tmax at all timepoints is reported.

Summarized data for t½ at all timepoints is reported.

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.

VUMERITY®

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).

The First Affiliated Hospital of Anhui Medical University

Beijing Hospital

Beijing Tiantan Hospital, Capital Medical University

Fujian Medical University Union Hospital

Lanzhou University Second Hospital

Dongguan People's Hospital

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou First People's Hospital

The Second Affiliated Hospital of Guangzhou Medical University

Nanfang Hospital of Southern Medical University

The Third Affiliated Hospital, Sun Yat-sen University

Tangshan Gongren Hospital

The First Affiliated Hospital of Harbin Medical University

The Second Affiliated Hospital of Harbin Medical University

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

Xiangya Hospital, Central South University

The Affiliated Hospital of Inner Mongolia Medical University

The First Affiliated Hospital of Soochow University

Jiangxi Provincial People's Hospital

The First Affiliated Hospital of Nanchang University

The First Hospital of Jilin University

Shengjing Hospital of China Medical University

General Hospital of Ningxia Medical University

Renji Hospital Shanghai Jiaotong University School of Medicine - West Branch

Shanxi Provincial People's Hospital

Tangdu Hospital, Fourth Military Medical University

Sichuan Provincial People's Hospital

Tianjin Medical University Affiliated General Hospital

First Affiliated Hospital of Kunming Medical University

Chiba University Hospital

Tokyo Womens Medical University Yachiyo Medical Center

Ehime University Hospital

Fukuoka University Hospital

Hospital of the University of Occupational and Environmental Health

Southern Tohoku Medical Clinic

NHO Asahikawa Medical Center

Obihiro Kosei Hospital

NHO Hokkaido Medical Center

University of Tsukuba Hospital

Iwate Medical University Uchimaru Medical Center

Yokohama City University Hospital

Tohoku University Hospital

Tohoku Medical and Pharmaceutical University Hospital

Niigata University Medical & Dental Hospital

Kansai Medical University Medical Center

Saitama Medical Center

Juntendo University Hospital

National Center of Neurology and Psychiatry

Ebara Hospital

Department of Neurosurgery, Tokyo Women's Medical University

Wakayama Medical University Hospital

Yamaguchi University Hospital

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.

Clinical laboratory parameters will include chemistry, hematology and urinalysis parameters.

Vital sign parameters will include temperature, pulse rate, systolic and diastolic blood pressure, and respiratory rate.

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").

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.