An Efficacy and Safety Study of BG00012 (Dimethyl Fumarate) in Asian Subjects With Relapsing Remitting Multiple Sclerosis (RRMS)

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of BG00012 in Subjects From the Asia-Pacific Region and Other Countries With Relapsing-Remitting Multiple Sclerosis

This is a multicenter study conducted in 2 parts:

The primary objective in Part I of this study is to determine the efficacy of BG00012 (dimethyl fumarate, DMF) on inflammatory brain magnetic resonance imaging (MRI) lesion activity (Gadolinium-enhancing lesions) when compared with placebo from 4 scans performed at Weeks 12, 16, 20, and 24 in participants with Relapsing Remitting Multiple Sclerosis (RRMS) including participants from the Asia-Pacific region.

The secondary objectives in Part I of this study in this study population are to determine whether BG00012, when compared with placebo over 24 weeks, is effective in reducing the cumulative number of new Gadolinium-enhancing lesions from Baseline to Week 24; reducing the number of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Week 24 compared with Baseline.

The primary objective in Part II (open label) of this study is to evaluate the long-term safety profile of BG00012 in eligible participants from Part I.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Relapsing-Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: dimethyl fumarate

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Havirov, Czechia, 736 00
    • Neurospol, s.r.o.
  • Hradec Kralove, Czechia, 500 05
    • Fakultní nemocnice Hradec Králové
  • Hradec Kralove, Czechia, 50003
    • Privatni ordinace - neurologie
  • Jihlava, Czechia, 58633
    • Nemocnice Jihlava
  • Olomouc, Czechia, 775 20
    • Fakultní nemocnice Olomouc
  • Praha 2, Czechia, 128 08
    • Fakultni Poliklinika VFN
  • Praha 5, Czechia, 150 06
    • Fakultní nemocnice v Motole
  • Teplice, Czechia, 41529
    • Krajska zdravotni, a.s. - Nemocnice Teplice, o.z.
• Japan
  • Asahikawa-shi, Japan, 070-8644
    • NHO Asahikawa Medical Center
  • Bunkyo-ku, Japan, 113-8431
    • Juntendo University Hospital
  • Chiba-shi, Japan, 260-8677
    • Chiba University Hospital
  • Fukuoka-shi, Japan, 812-8582
    • Kyushu University Hospital
  • Kahoku-gun, Japan, 920-0293
    • Kanazawa Medical University Hospital
  • Kawagoe-shi, Japan, 350-8550
    • Saitama Medical Center
  • Kobe-shi, Japan, 650-0017
    • Kobe University Hospital
  • Kodaira-shi, Japan, 187-8551
    • National Center Hospital, NCNP
  • Kyoto-shi, Japan, 606-8507
    • Kyoto University Hospital
  • Kyoto-shi, Japan, 616-8255
    • NHO Utano Hospital
  • Morioka-shi, Japan, 020-8505
    • Iwate Medical University Hospital
  • Niigata-shi, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Osaka-shi, Japan, 556-0016
    • Irino Clinic, Inc.
  • Osakasayama-shi, Japan, 589-8511
    • Kindai University Hospital
  • Ota-ku, Japan, 145-0065
    • Tokyotohokeniryokosya Ebara Hospital
  • Sapporo-shi, Japan, 063-0005
    • NHO Hokkaido Medical Center
  • Sapporo-shi, Japan, 065-0021
    • CEReS Sapporo Neurology Clinic
  • Sendai-shi, Japan, 980-8574
    • Tohoku University Hospital
  • Shinjuku-ku, Japan, 160-8582
    • Keio University Hospital
  • Shinjuku-ku, Japan, 162-8666
    • Department of Neurosurgery, Tokyo Women's Medical University
  • Suita-shi, Japan, 565-0871
    • Osaka University Hospital
  • Tokorozawa-shi, Japan, 359-8513
    • National Defense Medical College Hospital
  • Toon-shi, Japan, 791-0295
    • Ehime University Hospital
  • Tsukuba-shi, Japan, 305-8576
    • Tsukuba University Hospital
  • Ube-shi, Japan, 755-8505
    • Yamaguchi University Hospital
  • Yachiyo-shi, Japan, 276-8524
    • Tokyo Womens Medical University Yachiyo Medical Center
  • Yokohama-shi, Japan, 236-0004
    • Yokohama City University Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of, 42415
    • Yeungnam University Hospital
  • Gyeonggi-do, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Poland
  • Gdansk, Poland, 80-803
    • Copernicus Podmiot Leczniczy Sp. z o.o.
  • Katowice, Poland, 40-571
    • M.A. - LEK A.M.Maciejowscy SC.
  • Katowice, Poland, 40-650
    • NZOZ Novo-Med
  • Katowice, Poland, 40-749
    • Neuro-Care Gabriela Klodowska
  • Krakow, Poland, 31-637
    • MCD Medical
  • Lodz, Poland, 90-324
    • Centrum Neurologii K. Selmaj
  • Plewiska, Poland, 62-064
    • Neurologiczny NZOZ Centrum Leczenia SM
  • Poznan, Poland, 61-853
    • NZOZ "NEURO-KARD", "Ilkowski i Partnerzy" Sp. Partn. Lek.
  • Warszawa, Poland, 04-749
    • Miedzyleski Szpital Specjalistyczny
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Inclusion Criteria for Part I:

  • Must have a diagnosis of Relapsing-Remitting Multiple Sclerosis (RRMS).
  • Must have a baseline Expanded Disability Status Scale (EDSS) score between 0.0 and 5.0, inclusive.

Key Inclusion Criteria for Part II:

• Subjects who participated in and completed Part I per protocol.

Key Exclusion Criteria:

• Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease.
• Pregnant or nursing women.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part I Placebo; Placebo orally twice a day. In Part I: participants will be randomized into one of 2 groups: BG00012, 240 mg twice daily (BID) or matching placebo BID Participants will begin the study by taking 1 capsule orally BID for first 7 days and escalate their dosing from day 8 to 2 matching capsules orally BID.	Drug: Placebo; Two placebo capsules orally BID
Experimental: Part I BG00012; BG00012 240 mg orally twice a day (participants will begin dosing at 120 mg BG00012 twice daily (BID) for the first 7 days and 240 mg BG00012 BID thereafter.) In Part I: participants will be randomized into one of 2 groups: BG00012, 240 mg twice daily (BID) or matching placebo BID	Drug: dimethyl fumarate; Two dimethyl fumarate 120mg capsules orally BID; Other Names: BG00012; DMF; Tecfidera
Experimental: Part II BG00012; Part II: All participants will receive BG00012 240 mg orally twice a day (participants will begin dosing at 120 mg (1 capsule) BG00012 twice daily (BID) for the first 7 days and 240 mg (2 capsules) BG00012 BID thereafter.	Drug: dimethyl fumarate; Two dimethyl fumarate 120mg capsules orally BID; Other Names: BG00012; DMF; Tecfidera

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total number of new Gadolinium-enhancing lesions over 4 scans at Weeks 12, 16, 20, and 24.	Part I (Week 24)
Incidence of treatment-emergent adverse events and serious adverse events	Part II (Up to 4.5 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
Cumulative number of new Gadolinium-enhancing lesions from Baseline to Week 24	Part I (Week 24)
Number of new or newly enlarging T2 hyperintense lesions at Week 24 compared with Baseline	Part I (Week 24)

Collaborators and Investigators

• Sponsor: Biogen

Publications and helpful links

General Publications

• Kondo T, Kawachi I, Onizuka Y, Hiramatsu K, Hase M, Yun J, Matta A, Torii S. Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension. Mult Scler J Exp Transl Clin. 2019 Jul 31;5(3):2055217319864974. doi: 10.1177/2055217319864974. eCollection 2019 Jul-Sep.
• Saida T, Yamamura T, Kondo T, Yun J, Yang M, Li J, Mahadavan L, Zhu B, Sheikh SI. A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries. BMC Neurol. 2019 Jan 7;19(1):5. doi: 10.1186/s12883-018-1220-3.
• Ochi H, Niino M, Onizuka Y, Hiramatsu K, Hase M, Yun J, Matta A, Torii S. 72-Week Safety and Tolerability of Dimethyl Fumarate in Japanese Patients with Relapsing-remitting Multiple Sclerosis: Analysis of the Randomised, Double Blind, Placebo-Controlled, Phase III APEX Study and its Open-Label Extension. Adv Ther. 2018 Oct;35(10):1598-1611. doi: 10.1007/s12325-018-0788-8. Epub 2018 Sep 11.

Helpful Links

• EudraCT Tabulated Result

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2013
• Primary Completion (Actual): June 16, 2015
• Study Completion (Actual): September 4, 2018

Study Registration Dates

• First Submitted: April 20, 2013
• First Submitted That Met QC Criteria: April 20, 2013
• First Posted (Estimate): April 24, 2013

Study Record Updates

• Last Update Posted (Actual): November 20, 2018
• Last Update Submitted That Met QC Criteria: November 19, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Dimethyl Fumarate
• Other Study ID Numbers: 109MS305; 2013-004533-32 (EudraCT Number)