A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Diroximel Fumarate (DRF) in Chinese and Caucasian Adult Healthy Participants

An Open-Label, Parallel-Group, Phase 1 Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Diroximel Fumarate (BIIB098) in Chinese and Caucasian Adult Healthy Participants

The primary objective is to evaluate the primary pharmacokinetic (PK) parameters of DRF active metabolite monomethyl fumarate (MMF) following multiple doses of DRF in Chinese and Caucasian adult healthy participants. The secondary objectives are to evaluate the secondary PK parameters of DRF active metabolite MMF following multiple doses of DRF in Chinese and Caucasian adult healthy participants, to evaluate the PK of DRF inactive major metabolite 2-hydroxyethyl succinimide (HES) following multiple doses of DRF in Chinese and Caucasian adult healthy participants and to evaluate the safety and tolerability of multiple oral doses of DRF in Chinese and Caucasian adult healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Diroximel fumarate

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • New Territories
    • Sha Tin, New Territories, Hong Kong
      • Research Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Have a body mass index (BMI) between 18 and 30 kilograms per meter square (kg/m^2), inclusive.
• Negative polymerase chain reaction (PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening and Day -1.
• For Chinese participants: was born in China, and biological parents and grandparents were of Chinese origin. If living outside China for more than 5 years, must not have had a significantly modified diet since leaving China.

Key Exclusion Criteria:

• 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; or systemic hypersensitivity reactions to DRF, dimethyl fumarate (DMF), MMF, other fumaric esters, excipients in the formulation, or diagnostic agents to be administered during the study.
• Confirmed demonstration of corrected QT interval, using Fridericia's correction method, of >450 milliseconds (ms) for males and >460 ms for females.
• 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.
• Has experienced clinically significant acute GI symptoms in the judgment of the investigator within 30 days prior to admission.
• History or positive test result at screening for human immunodeficiency virus (HIV).
• Chronic, recurrent, or serious infection, as determined by the investigator, within 90 days prior to screening and between screening and Day -1.
• Current enrollment in any other drug, biological, device, or clinical study or treatment with an investigational drug or approved therapy for investigational use within 30 days prior to Day -1, or 5 half-lives, whichever is longer.
• Previous participation in this study or previous studies with DRF or DMF.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DRF: Chinese Participants; Chinese participants will receive DRF Dose 1, oral capsules, twice daily (BID), from Day 1 to Day 4 and DRF Dose 1, oral capsules, once daily (QD), on Day 5.	Drug: Diroximel fumarate; Administered as specified in the treatment arm; Other Names: BIIB098; Vumerity
EXPERIMENTAL: DRF: Caucasian Participants; Caucasian participants will receive DRF Dose 1, oral capsules, BID, from Day 1 to Day 4 and DRF Dose 1, oral capsules, QD, on Day 5.	Drug: Diroximel fumarate; Administered as specified in the treatment arm; Other Names: BIIB098; Vumerity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Concentration (Cmax) of Monomethyl Fumarate (MMF)	Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Area Under the Concentration-Time Curve within a Dosing Interval (AUCtau) of MMF	Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Reach Maximum Observed Concentration (Tmax) of MMF		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Elimination Half-Life (t½) of MMF		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Lag Time in Absorption (Tlag) of MMF		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Apparent Total Body Clearance (CL/F) of MMF		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Apparent Volume of Distribution (Vz/F) of MMF		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Accumulation Ratio Following Multiple Dosing (Rac) of MMF		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Maximum Observed Concentration (Cmax) of 2-Hydroxyethyl Succinimide (HES)		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Area Under the Concentration-Time Curve within a Dosing Interval (AUCtau) of HES		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Time to Reach Maximum Observed Concentration (Tmax) of HES		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Elimination Half-Life (t½) of HES		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Lag Time in Absorption (Tlag) of HES		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Apparent Total Body Clearance (CL/F) of HES		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Apparent Volume of Distribution (Vz/F) of HES		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Accumulation Ratio Following Multiple Dosing (Rac) of HES		Pre-dose and at multiple timepoints post-dose on Days 1 and 5 and post-dose on Days 6, 7 and 8
Number of Participants with Adverse Events (AEs)	An adverse event (AE) is any untoward medical occurrence in a patient or 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.	Day 1 to Day 10
Number of Participants with Serious Adverse Events (SAEs)	A serious adverse event (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.	Screening to Day 10

Collaborators and Investigators

• Sponsor: Biogen

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 3, 2021
• Primary Completion (ACTUAL): June 9, 2022
• Study Completion (ACTUAL): June 29, 2022

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: November 9, 2021
• First Posted (ACTUAL): November 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): July 5, 2022
• Last Update Submitted That Met QC Criteria: July 1, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 272HV111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on http://clinicalresearch.biogen.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No