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

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— ENDORSE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00835770
• Other study ID #: 109MS303
• Secondary ID: 2008-004753-14
• Status: Completed
• Phase: Phase 3
• Start date: February 3, 2009
• Est. completion date: November 8, 2019

Study information

• Verified date: December 2020
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1736
• Est. completion date: November 8, 2019
• Est. primary completion date: November 8, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 58 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• dimethyl fumarate
BG00012 capsules
• Placebo
Capsules taken to maintain the blind in the 240 mg BID treatment group.

Locations

Country	Name	City	State
Australia	Research Site	Box Hill
Australia	Research Site	Chatswood
Australia	Research Site	Fitzroy
Australia	Research Site	Geelong
Australia	Research Site	Kogarah	New South Wales
Australia	Research Site	Melbourne	Victoria
Australia	Research Site	New Lambton Heights	New South Wales
Australia	Research Site	Sydney
Austria	Research Site	Graz
Austria	Research Site	Linz
Austria	Research Site	Vienna
Belarus	Research Site	Belarus	Gomel
Belarus	Research Site	Belarus	Vitebsk
Belarus	Research Site	Minsk
Belarus	Research Site	Minsk
Belgium	Research Site	Antwerpen
Belgium	Research Site	Brugge
Belgium	Research Site	Brussels
Belgium	Research Site	Charleroi
Belgium	Research Site	Damme
Belgium	Research Site	Diepenbeek
Belgium	Research Site	Hechtel-Eksel
Belgium	Research Site	Leuven
Belgium	Research Site	Lodelinsart
Belgium	Research Site	Sint-Truiden
Bosnia and Herzegovina	Research Site	Tuzla
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	Edmonton
Canada	Research Site	Lévis	Quebec
Canada	Research Site	London
Canada	Research Site	Montreal
Canada	Research Site	Nova Scotia
Canada	Research Site	Ottawa
Canada	Research Site	Regina
Croatia	Research Site	Zagreb
Czechia	Research Site	Brno
Czechia	Research Site	Jihlava
Czechia	Research Site	Moravska Ostrava
Czechia	Research Site	Olomouc
Czechia	Research Site	Opava
Czechia	Research Site	Ostrava - Vítkovice
Czechia	Research Site	Prague
Czechia	Research Site	Prague
Czechia	Research Site	Teplice
Estonia	Research Site	Parnu
Estonia	Research Site	Tallinn
Estonia	Research Site	Tallinn
Estonia	Research Site	Tartu
France	Research Site	Amiens
France	Research Site	Caen
France	Research Site	Clermont-Ferrand
France	Research Site	Dijon
France	Research Site	Lille
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Nancy
France	Research Site	Nice
France	Research Site	Paris
France	Research Site	Rennes
France	Research Site	Strasbourg
Germany	Research Site	Bayreuth
Germany	Research Site	Berg	Bavaria
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bochum
Germany	Research Site	Dresden
Germany	Research Site	Dusseldorf
Germany	Research Site	Erbach
Germany	Research Site	Erlangen
Germany	Research Site	Essen
Germany	Research Site	Halle
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Hannover
Germany	Research Site	Koeln
Germany	Research Site	Leipzig
Germany	Research Site	Magdeburg
Germany	Research Site	Marburg
Germany	Research Site	Minden
Germany	Research Site	Munich (München)
Germany	Research Site	Münster
Germany	Research Site	Osnabrück
Germany	Research Site	Regensburg
Germany	Research Site	Steinfurt	Ibbenbueren
Germany	Research Site	Westerstede
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Greece	Research Site	Thessaloniki
India	Research Site	Ahmedabad
India	Research Site	Bangalore
India	Research Site	Chandigarh
India	Research Site	Hyderabad
India	Research Site	Kolkata
India	Research Site	Kolkata
India	Research Site	Ludhiana
India	Research Site	Ludhiana
India	Research Site	Mangalore
India	Research Site	Mumbai
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	New Delhi
India	Research Site	Pune
India	Research Site	Pune
Ireland	Research Site	Dublin
Israel	Research Site	Ashkelon
Israel	Research Site	Jerusalem
Israel	Research Site	Safed
Italy	Research Site	Roma
Latvia	Research Site	Riga
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico
Mexico	Research Site	Mexico
Mexico	Research Site	Morelia
Mexico	Research Site	San Luis Potosi
Moldova, Republic of	Research Site	Chisinau
Moldova, Republic of	Research Site	Chisinau
Netherlands	Research Site	Breda
Netherlands	Research Site	Geleen
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Hamilton
North Macedonia	Research Site	Skopje
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Katowice
Poland	Research Site	Katowice
Poland	Research Site	Krakow
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olsztyn
Poland	Research Site	Plewiska
Poland	Research Site	Poznan
Poland	Research Site	Poznan
Poland	Research Site	Szczecin
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Puerto Rico	Research Site	Guaynabo
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Bucuresti
Romania	Research Site	Cluj-Napoca
Romania	Research Site	Târgu Mures
Romania	Research Site	Timisoara
Serbia	Research Site	Belgrade
Serbia	Research Site	Kragujevac
Serbia	Research Site	Nis
Serbia	Research Site	Novi Sad
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Bratislava
Slovakia	Research Site	Martin
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
Spain	Research Site	Barcelona
Spain	Research Site	Córdoba
Spain	Research Site	Madrid
Spain	Research Site	Malaga
Spain	Research Site	Sevilla
Switzerland	Research Site	Basel
Switzerland	Research Site	St. Gallen
Switzerland	Research Site	Zurich
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odessa
Ukraine	Research Site	Poltava
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhia
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Newcastle upon Tyne
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Stoke on Trent
United States	Research Site	Albany	New York
United States	Research Site	Amherst	New York
United States	Research Site	Atlanta	Georgia
United States	Research Site	Atlanta	Georgia
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bellevue	Ohio
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boulder	Colorado
United States	Research Site	Buffalo	New York
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chesterfield	Missouri
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Cordova	Tennessee
United States	Research Site	Dayton	Ohio
United States	Research Site	Evanston	Illinois
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Fort Collins	Colorado
United States	Research Site	Fort Wayne	Indiana
United States	Research Site	Houston	Texas
United States	Research Site	Huntsville	Alabama
United States	Research Site	Issaquah	Washington
United States	Research Site	Kansas City	Kansas
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Loma Linda	California
United States	Research Site	Madison	Wisconsin
United States	Research Site	Maitland	Florida
United States	Research Site	Medford	Oregon
United States	research Site	Mesa	Arizona
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Naples	Florida
United States	Research Site	Newport News	Virginia
United States	Research Site	North Haven	Connecticut
United States	Research Site	Patchogue	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Raleigh	North Carolina
United States	Research Site	Rumford	Rhode Island
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Sarasota	Florida
United States	Research Site	Shreveport	Louisiana
United States	Research Site	Tampa	Florida
United States	Research Site	Washington	District of Columbia
United States	Research Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belarus,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  Canada,  Croatia,  Czechia,  Estonia,  France,  Germany,  Greece,  India,  Ireland,  Israel,  Italy,  Latvia,  Mexico,  Moldova, Republic of,  Netherlands,  New Zealand,  North Macedonia,  Poland,  Puerto Rico,  Romania,  Serbia,  Slovakia,  South Africa,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (AEs)	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	Day 1 up to Week 561
Secondary	Percentage of Participants Who Had Relapses	Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours.	Day 1 up to Week 384
Secondary	Annualized Relapse Rate (ARR)	The annualized relapse rate is calculated as the total number of relapses occurred during the period for all participants, divided by the total number of participant-years followed in the period.	Day 1 up to Week 384
Secondary	Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384	EDSS scale ranges from 0 (Normal neurological exam, no disability) to 10 (Death) in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. Sustained disability progression was defined as at least a 1.0 point increase on the EDSS from a baseline EDSS =1.0 that was sustained for at least 24 weeks, or a 1.5 point increase on the EDSS from a baseline EDSS =0 that was sustained for at least 24 weeks.	Baseline, Week 384
Secondary	Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)	The Gd-enhancing lesions was evaluated using MRI technique.	Baseline up to Week 288
Secondary	Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)	The Gd-enhancing lesions was evaluated using MRI technique.	Baseline up to Week 288
Secondary	Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)	The T2 lesions was evaluated using MRI technique.	Baseline up to Week 288
Secondary	Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)	The T2 lesions was evaluated using MRI technique.	Baseline up to Week 288
Secondary	Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)	The T1 hypointense lesions was evaluated using MRI technique.	Baseline up to Week 288
Secondary	Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)	The T1 hypointense lesions was evaluated using MRI technique.	Baseline up to Week 288
Secondary	Percent Change From Baseline in Brain Atrophy	Brain atrophy was measured using magnetic resonance imaging (MRI) technique.	Baseline up to Week 288
Secondary	Percent Change From Baseline in Magnetization Transfer Ratio (MTR)	Magnetization Transfer Ratio (MTR) was measured using MRI technique.	Baseline up to Week 288
Secondary	Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384	The SF-36 is a brief (36-item) scale reflecting the impact of both dysfunctions and general health perception the questionnaire measures: 1.physical function (PF),2. role physical (RF),3. bodily pain (BP),4. role emotional (RE),5. social function (SF), 6. general health (GH),7. vitality (VT), 8. mental health (MH). Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. The questions related to each dimension are scored on a scale from 0 (worst score) to 100 (best score), with higher scores indicating better function.	Baseline, Week 384
Secondary	Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384	The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. The EQ-5D provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has (1) "no problems", (2) "some problems", or (3) "severe problems". A positive change from baseline indicates improvement.	Baseline, Week 384
Secondary	Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384	The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. In EQ-VAS participants are asked to rate their current health on a 20 centimeter (cm) scale from 0 to 100 where 0 represents "worst imaginable health state" and 100 represents "best imaginable health state". A positive change from baseline indicates improvement.	Baseline, Week 384
Secondary	Change From Baseline in Visual Function Test Scores at Week 384	Participants were tested using the contrast level of 100%, 2.5%, and 1.25% charts, and the scores were defined as the number of letters identified correctly for each chart (the maximum score was 60). Higher scores indicate better functioning. A positive change from baseline indicates better functioning.	Baseline, Week 384