A Dose-Blind, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of Two Doses of BG00012 Monotherapy in Subjects With Relapsing-Remitting Multiple Sclerosis

BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (MS)



Sponsors

Lead Sponsor



Source

Biogen

Oversight Info

Authority

Israel: Ministry of Health

Belgium: Federal Agency for Medicinal Products and Health Products

Bulgaria: Bulgarian Drug Agency

Romania: National Agency for Medicines and Medical Devices

Switzerland: Swissmedic

Ukraine: State Pharmacological Center - Ministry of Health

Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Macedonia: Ministry of Health

Spain: Agencia Española de Medicamentos y Productos Sanitarios

Guatemala: Ministry of Public Health and Social Assistance

Australia: Department of Health and Ageing Therapeutic Goods Administration

New Zealand: Ministry of Health

Bosnia: Federal Ministry of Health

Serbia: Medicines and Medical Devices Agency of Serbia

Italy: The Italian Medicines Agency

Mexico: Federal Commission for Sanitary Risks Protection

Estonia: The State Agency of Medicine

Austria: Agency for Health and Food Safety

South Africa: Medicines Control Council

Czech Republic: State Institute for Drug Control

Greece: National Organization of Medicines

Slovakia: State Institute for Drug Control

Germany: Federal Institute for Drugs and Medical Devices

Croatia: Ministry of Health and Social Care

Belarus: Ministry of Health

Canada: Health Canada

Ireland: Health Products Regulatory Authority

France: Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM)

Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

United States: Food and Drug Administration

India: Drugs Controller General of India

Latvia: State Agency of Medicines

United Kingdom: Medicines and Healthcare Products Regulatory Agency

Moldova: Ministry of Health


Has Dmc

No


Brief Summary

The primary objective of this study is to evaluate the long-term safety profile of BG00012
(dimethyl fumarate). Secondary objectives of this study are to evaluate the long-term
efficacy of BG00012 using clinical endpoints and disability progression, to evaluate further
the long-term effects of BG00012 on multiple sclerosis (MS) brain lesions on magnetic
resonance imaging (MRI) scans in participants who had MRI scans as part of Studies 109MS301
(NCT00420212) and 109MS302 (NCT00451451) and to evaluate the long-term effects of BG00012 on
health economics assessments and the visual function test.

Detailed Description

The initial BG00012 dosage for the extension study (240 mg BID or 240 mg TID) was the same
as that used in the Phase 3 Studies 109MS301 (NCT00420212) and 109MS302 (NCT00451451).
Subsequent to the initiation of this study, BG00012 was approved in several countries for
the treatment of MS at a dose of 240 mg BID. For this reason, all participants continuing in
this study will receive the currently marketed dose of 240 mg BID.

Overall Status

Active, not recruiting

Start Date

2009-02-01

Completion Date

2023-02-01

Primary Completion Date

2023-02-01

Phase

Phase 3

Study Type

Interventional

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Primary Outcome

Measure

Time Frame

Safety Issue

Number of Participants with Adverse Events
Day 1 up to 12 years
Yes

Secondary Outcome

Measure

Time Frame

Safety Issue

Number of Participants Who Had Relapses
Day 1 up to 12 years
No
Annualized Relapse Rate (ARR)
Day 1 up to 12 years
No
Change from Baseline in the Expanded Disability Status Scale (EDSS) up to 12 years
Day 1 up to 12 years
No
Number and volume of Gd-enhancing lesions as Measured by Magnetic Resonance Imaging (MRI)
Day 1 up to 12 years
No
Number and volume of new or newly-enlarging T2 lesions as Measured by Magnetic Resonance Imaging (MRI)
Day 1 up to 12 years
No
Number and volume of T1 hypointense lesions
Day 1 to 12 years
No
Change from Baseline in Brain atrophy up to 12 years
Day 1 to 12 years
No
Summary of Magnetization Transfer Ratio (MTR)
Day 1 to 12 years
No
Change from Baseline in EQ-5D Health Survey (EQ-5D) up to 12 years
Day 1 to 12 years
No
Change from baseline in SF-36® Health Survey (SF-36) up to 12 years
Day 1 to 12 years
No
Change from Baseline in Visual Function test scores up to 12 years
Day 1 to 12 years
No

Enrollment

1738

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

BG00012 capsules

Arm Group Label

BG00012

BG00012 plus placebo


Other Name

BG00012

Tecfidera

DMF



Intervention Type

Drug

Intervention Name


Description

Capsules taken to maintain the blind in the 240 mg BID treatment group.

Arm Group Label

BG00012 plus placebo



Eligibility

Criteria

Key Inclusion Criteria:

-Subjects who participated in and completed as per protocol previous BG00012 clinical
studies 109MS301 (NCT00420212) or 109MS302 (NCT00451451).

Key Exclusion Criteria:

- Any significant change in medical history from 109MS301 or 109MS302 that would have
excluded subject's participation from their previous study.

- Subjects from 109MS301 or 109MS302 who discontinued oral study treatment due to an AE
or due to reasons other than protocol-defined relapse/disability progression.

- Subjects from 109MS301 or 109MS302 who discontinued study treatment due to disability
progression or relapses and did not follow the modified visit schedule up to Week 96.

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

Gender

Both

Minimum Age

19 Years

Maximum Age

58 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Medical Director
Study Director
Biogen

Location

Facility

Research Site
Birmingham Alabama 35294 United States
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Huntsville Alabama 35801 United States
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Mesa Arizona 85206 United States
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Phoenix Arizona 85001 United States
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Phoenix Arizona 85013 United States
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Loma Linda California 92354 United States
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Sacramento California 94207 United States
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Boulder Colorado 80304 United States
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Colorado Springs Colorado 80903 United States
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Fort Collins Colorado 80528 United States
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North Haven Connecticut 06473 United States
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Washington District of Columbia 20007 United States
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Maitland Florida 32751 United States
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Miami Florida 33136 United States
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Naples Florida 34102 United States
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Saint Petersburg Florida 33709 United States
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Sarasota Florida 34239 United States
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Tampa Florida 33612 United States
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Vero Beach Florida 32964 United States
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Atlanta Georgia 30309 United States
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Atlanta Georgia 30327 United States
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Evanston Illinois 60201 United States
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Fort Wayne Indiana 46845 United States
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Indianapolis Indiana 46256 United States
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Des Moines Iowa 50309 United States
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Kansas City Kansas 66160 United States
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Wichita Kansas 67206 United States
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Lexington Kentucky 40504 United States
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Louisville Kentucky 40201 United States
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Shreveport Louisiana 71103 United States
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Baltimore Maryland 21201 United States
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Boston Massachusetts 02135 United States
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Boston Massachusetts 02215 United States
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Hopedale Massachusetts 01747 United States
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Springfield Massachusetts 01104 United States
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Farmington Hills Michigan 48334 United States
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Minneapolis Minnesota 55414 United States
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Chesterfield Missouri 63017 United States
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St. Louis Missouri 63104 United States
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Albany New York 12206 United States
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Amherst New York 14226 United States
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Buffalo New York 14203 United States
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Patchogue New York 11772 United States
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Charlotte North Carolina 28204 United States
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Raleigh North Carolina 27607 United States
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Bellevue Ohio 44811 United States
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Cleveland Ohio 44195 United States
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Columbus Ohio 43221 United States
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Dayton Ohio 45417 United States
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Medford Oregon 97504 United States
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Portland Oregon 97225 United States
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Erie Pennsylvania 16503 United States
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Philadelphia Pennsylvania 19104 United States
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Philadelphia Pennsylvania 19140 United States
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Pittsburgh Pennsylvania 15203 United States
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Pittsburg Pennsylvania 15213 United States
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Rumford Rhode Island 02916 United States
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Cordova Tennessee 38018 United States
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Knoxville Tennessee 37922 United States
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Nashville Tennessee 37201 United States
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Dallas Texas 75203 United States
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Houston Texas 77030 United States
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Salt Lake City Utah 84101 United States
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Burlington Vermont 05401 United States
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Issaquah Washington 98029 United States
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Tacoma Washington 98405 United States
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Madison Wisconsin 53792 United States
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Box Hill 3128 Australia
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Camperdown 2000 Australia
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Chatswood 2067 Australia
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Fitzroy 3065 Australia
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Geelong 3220 Australia
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Heidelberg 3084 Australia
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Kogarah 2217 Australia
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New Lambton Heights 2305 Australia
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Graz 8036 Austria
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Linz 4021 Austria
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Vienna 1090 Austria
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Gomel 246029 Belarus
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Minsk 220114 Belarus
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Minsk 220116 Belarus
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Vitebsk 210023 Belarus
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Antwerpen 2020 Belgium
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Brugge 8000 Belgium
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Brussels 1200 Belgium
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Charleroi 6000 Belgium
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Diepenbeek 3590 Belgium
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Hechtel-Eksel 3940 Belgium
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Leuven 3000 Belgium
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Sijsele-Damme 8340 Belgium
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Tuzla 75000 Bosnia and Herzegovina
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Ruse 7002 Bulgaria
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Sofia 1113 Bulgaria
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Sofia 1309 Bulgaria
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Sofia 1431 Bulgaria
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Edmonton T6G 2G3 Canada
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Halifax B3H 4K4 Canada
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London N6A 5A5 Canada
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Lévis G6V 3Z1 Canada
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Montreal H3A 2B4 Canada
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Ottawa K2G 6E2 Canada
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Regina S4T 7T1 Canada
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Zagreb 10000 Croatia
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Brno 656 91 Czech Republic
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Jihlava 586 33 Czech Republic
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Moravska Ostrava 702 00 Czech Republic
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Olomouc 775 20 Czech Republic
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Opava 746 01 Czech Republic
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Ostrava - Vítkovice 70300 Czech Republic
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Praha 2 128 08 Czech Republic
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Praha 5 150 06 Czech Republic
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Teplice 415 01 Czech Republic
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Parnu 80010 Estonia
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Tallinn 10138 Estonia
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Tallinn 10617 Estonia
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Tartu 51014 Estonia
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Amiens 80054 France
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Caen 14033 France
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Clermont-Ferrand 63003 France
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Dijon 21033 France
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Lille 59037 France
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Lyon 69394 France
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Marseille 13385 France
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Montpellier 34295 France
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Nancy 54035 France
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Nice 06002 France
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Paris 75019 France
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Rennes 35033 France
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Strasbourg 67000 France
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Bamberg Bayern Germany
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Munich (München) Bayern 81377 Germany
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München Bayern Germany
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Bayreuth 95445 Germany
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Berg 82335 Germany
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Berlin 10437 Germany
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Berlin 10625 Germany
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Berlin 10961 Germany
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Berlin 12099 Germany
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Berlin 12163 Germany
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Berlin 13347 Germany
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Bochum 44791 Germany
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Dresden 01307 Germany
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Düsseldorf 40212 Germany
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Erbach 64711 Germany
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Erlangen 91054 Germany
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Essen 45257 Germany
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Halle 06120 Germany
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Hamburg 20099 Germany
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Hamburg 20246 Germany
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Hamburg 22083 Germany
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Hannover 30171 Germany
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Hannover 30625 Germany
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Ibbenbueren 49477 Germany
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Koeln 50935 Germany
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Leipzig 04103 Germany
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Magdeburg 39120 Germany
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Marburg 35043 Germany
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Minden 32429 Germany
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Muenster 48149 Germany
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München 81675 Germany
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Osnabrück 49076 Germany
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Regensburg 93053 Germany
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Westerstede 26655 Germany
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Athens 11527 Greece
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Thessaloniki 54636 Greece
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Thessaloniki 57010 Greece
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Guatemala City Guatemala
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Guatemala Guatemala
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Ahmedabad 380006 India
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Bangalore 560054 India
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Chandigarh 160012 India
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Hyderabad 500082 India
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Kolkata 700054 India
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Kolkata 700068 India
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Ludhiana 141001 India
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Ludhiana 141008 India
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Mangalore 575002 India
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Mumbai 400054 India
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New Delhi 110017 India
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New Delhi 110029 India
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New Delhi 110060 India
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Pune 411001 India
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Pune 411004 India
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Dublin DUBLIN 4 Ireland
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Ashkelon 78278 Israel
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Jerusalem 9112001 Israel
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Safed 13100 Israel
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Roma 00189 Italy
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Riga LV-1015 Latvia
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Skopje 1000 Macedonia, The Former Yugoslav Republic of
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Guadalajara 44610 Mexico
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Mexico 03310 Mexico
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Mexico 06700 Mexico
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Morelia 58000 Mexico
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San Luis Potosi 78240 Mexico
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Chisinau 2001 Moldova, Republic of
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Chisinau 2028 Moldova, Republic of
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Breda 4818 CK Netherlands
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Sittard-Geleen 6162 BG Netherlands
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Auckland 1023 New Zealand
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Christchurch 8011 New Zealand
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Hamilton 3204 New Zealand
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Bialystok 15-276 Poland
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Gdansk 80-299 Poland
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Katowice 40-594 Poland
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Krakow 31-505 Poland
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Lódz 90-153 Poland
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Olsztyn 10-561 Poland
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Poznan 60-355 Poland
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Szczecin 70-215 Poland
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Warszawa 02-097 Poland
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Wroclaw 50-556 Poland
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Guaynabo 00968 Puerto Rico
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Bucuresti 011464 Romania
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Bucuresti 020125 Romania
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Bucuresti 022104 Romania
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Bucuresti 050098 Romania
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Cluj-Napoca 400012 Romania
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Timisoara 300736 Romania
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Târgu Mures 540136 Romania
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Belgrade 11000 Serbia
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Kragujevac 34000 Serbia
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Nis 18000 Serbia
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Novi Sad 21000 Serbia
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Bratislava 81369 Slovakia
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Bratislava 82606 Slovakia
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Martin 03659 Slovakia
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Rosebank Gauteng South Africa
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Cape Town 7925 South Africa
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Durban 4001 South Africa
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Barcelona 08035 Spain
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Córdoba 14011 Spain
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Madrid 28040 Spain
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Malaga 29010 Spain
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Sevilla 41009 Spain
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Basel 4031 Switzerland
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St. Gallen 9007 Switzerland
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Zurich 8091 Switzerland
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Simferopol Crimea Ukraine
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Ivano-Frankivsk 76018 Ukraine
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Kharkiv 61068 Ukraine
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Kharkiv 61103 Ukraine
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Kyiv 03110 Ukraine
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Kyiv 04112 Ukraine
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Lviv 79010 Ukraine
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Odessa 65117 Ukraine
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Poltava 36011 Ukraine
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Vinnytsia 21005 Ukraine
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Zaporizhzhia 69600 Ukraine
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London E1 4AT United Kingdom
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London SE5 9NT United Kingdom
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London W6 8RF United Kingdom
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Newcastle upon Tyne NE1 4HH United Kingdom
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Oxford OX3 9DU United Kingdom
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Sheffield S10 2JF United Kingdom
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Stoke on Trent ST4 6QG United Kingdom

Location Countries

Country

Australia

Austria

Belarus

Belgium

Bosnia and Herzegovina

Bulgaria

Canada

Croatia

Czech Republic

Estonia

France

Germany

Greece

Guatemala

India

Ireland

Israel

Italy

Latvia

Macedonia, The Former Yugoslav Republic of

Mexico

Moldova, Republic of

Netherlands

New Zealand

Poland

Puerto Rico

Romania

Serbia

Slovakia

South Africa

Spain

Switzerland

Ukraine

United Kingdom

United States



Verification Date

2016-07-01

Lastchanged Date

2016-07-27

Firstreceived Date

2009-02-02

Responsible Party

Responsible Party Type

Sponsor


Keywords


Is Fda Regulated

Yes

Has Expanded Access

No

Condition Browse


Secondary Id

2008-004753-14

Number Of Arms

2

Intervention Browse

Mesh Term

Dimethyl Fumarate


Is Section 801

Yes

Arm Group

Arm Group Label

BG00012 plus placebo

Arm Group Type

Experimental

Description

In the first phase, participants will receive BG00012 240 mg (two 120 mg capsules) twice a day (BID) and 2 placebo capsules once a day. In the second phase participants will receive open-label BG00012 240 mg BID, for up to 12 years.


Arm Group Label

BG00012

Arm Group Type

Experimental

Description

In the first phase participants will receive BG00012 240 mg (two 120 mg capsules) three times a day (TID). In the second phase participants will receive open-label BG00012 240 mg BID for up to 12 years.



Firstreceived Results Date

N/A

Acronym

ENDORSE

Firstreceived Results Disposition Date

N/A


ClinicalTrials.gov processed this data on September 13, 2016

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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