Clinical trial NCT00835770: BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (MS)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: relapsing
multiple sclerosis
remitting
oral
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2009-02-04
Enrollment: 1736
Sex: ALL
Minimum age (years): 19
Maximum age (years): 58
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: Day 1 up to Week 561
Secondary outcomes:
measure: Percentage of Participants Who Had Relapses
timeFrame: Day 1 up to Week 384
measure: Annualized Relapse Rate (ARR)
timeFrame: Day 1 up to Week 384
measure: Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384
timeFrame: Baseline, Week 384
measure: Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Week 288
measure: Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Week 288
measure: Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Week 288
measure: Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Week 288
measure: Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Week 288
measure: Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline up to Week 288
measure: Percent Change From Baseline in Brain Atrophy
timeFrame: Baseline up to Week 288
measure: Percent Change From Baseline in Magnetization Transfer Ratio (MTR)
timeFrame: Baseline up to Week 288
measure: Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384
timeFrame: Baseline, Week 384
measure: Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384
timeFrame: Baseline, Week 384
measure: Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384
timeFrame: Baseline, Week 384
measure: Change From Baseline in Visual Function Test Scores at Week 384
timeFrame: Baseline, Week 384
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Mesa
country: United States
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state: Arizona
city: Phoenix
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state: Arizona
city: Loma Linda
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state: California
city: Boulder
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state: Colorado
city: Fort Collins
country: United States
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state: Colorado
city: North Haven
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state: Connecticut
city: Washington
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state: District of Columbia
city: Maitland
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state: Florida
city: Miami
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city: Naples
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city: Sarasota
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state: Georgia
city: Evanston
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state: Illinois
city: Fort Wayne
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city: Kansas City
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city: Boston
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city: Farmington Hills
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city: Minneapolis
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city: Chesterfield
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city: Amherst
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city: Patchogue
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city: Charlotte
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state: North Carolina
city: Raleigh
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country: Australia
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city: New Lambton Heights
country: Australia
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state: New South Wales
city: Melbourne
country: Australia
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state: Victoria
city: Box Hill
country: Australia
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city: Chatswood
country: Australia
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city: Fitzroy
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city: Geelong
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city: Graz
country: Austria
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city: Linz
country: Austria
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city: Vienna
country: Austria
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city: Belarus
country: Belarus
facility: Research Site
state: Gomel
city: Belarus
country: Belarus
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state: Vitebsk
city: Minsk
country: Belarus
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city: Minsk
country: Belarus
facility: Research Site
city: Antwerpen
country: Belgium
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city: Brugge
country: Belgium
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city: Brussels
country: Belgium
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city: Charleroi
country: Belgium
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city: Damme
country: Belgium
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city: Diepenbeek
country: Belgium
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city: Hechtel-Eksel
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
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city: Lodelinsart
country: Belgium
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city: Sint-Truiden
country: Belgium
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city: Tuzla
country: Bosnia and Herzegovina
facility: Research Site
city: Ruse
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Sofia
country: Bulgaria
facility: Research Site
city: Lévis
country: Canada
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state: Quebec
city: Edmonton
country: Canada
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country: Canada
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city: Nova Scotia
country: Canada
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city: Ottawa
country: Canada
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city: Regina
country: Canada
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city: Zagreb
country: Croatia
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city: Brno
country: Czechia
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city: Jihlava
country: Czechia
facility: Research Site
city: Moravska Ostrava
country: Czechia
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city: Olomouc
country: Czechia
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city: Opava
country: Czechia
facility: Research Site
city: Ostrava - Vítkovice
country: Czechia
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city: Prague
country: Czechia
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country: Czechia
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country: Estonia
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city: Tallinn
country: Estonia
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country: Estonia
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country: Estonia
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country: France
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country: France
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country: France
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country: France
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country: France
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country: France
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country: France
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country: France
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country: France
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city: Rennes
country: France
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country: France
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city: Berg
country: Germany
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state: Bavaria
city: Steinfurt
country: Germany
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state: Ibbenbueren
city: Bayreuth
country: Germany
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city: Berlin
country: Germany
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country: Germany
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country: Germany
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city: Berlin
country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Germany
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city: Minden
country: Germany
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city: Munich (München)
country: Germany
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country: Germany
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city: Osnabrück
country: Germany
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city: Regensburg
country: Germany
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city: Westerstede
country: Germany
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city: Athens
country: Greece
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city: Thessaloniki
country: Greece
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city: Thessaloniki
country: Greece
facility: Research Site
city: Ahmedabad
country: India
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city: Bangalore
country: India
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country: India
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city: Hyderabad
country: India
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city: Kolkata
country: India
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city: Kolkata
country: India
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city: Ludhiana
country: India
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city: Ludhiana
country: India
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city: Mangalore
country: India
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city: Mumbai
country: India
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city: New Delhi
country: India
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city: New Delhi
country: India
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city: New Delhi
country: India
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city: Pune
country: India
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city: Pune
country: India
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city: Dublin
country: Ireland
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city: Ashkelon
country: Israel
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country: Israel
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city: Safed
country: Israel
facility: Research Site
city: Roma
country: Italy
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city: Riga
country: Latvia
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city: Guadalajara
country: Mexico
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city: Mexico
country: Mexico
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country: Mexico
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city: Mexico
country: Mexico
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city: Morelia
country: Mexico
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city: San Luis Potosi
country: Mexico
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city: Chisinau
country: Moldova, Republic of
facility: Research Site
city: Chisinau
country: Moldova, Republic of
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city: Breda
country: Netherlands
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city: Geleen
country: Netherlands
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city: Auckland
country: New Zealand
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country: New Zealand
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country: New Zealand
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country: North Macedonia
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city: Bialystok
country: Poland
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country: Poland
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city: Gdansk
country: Poland
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country: Poland
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country: Poland
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city: Katowice
country: Poland
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city: Katowice
country: Poland
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city: Krakow
country: Poland
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city: Lublin
country: Poland
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country: Poland
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country: Poland
facility: Research Site
city: Plewiska
country: Poland
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city: Poznan
country: Poland
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city: Poznan
country: Poland
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city: Szczecin
country: Poland
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city: Szczecin
country: Poland
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city: Warszawa
country: Poland
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city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Guaynabo
country: Puerto Rico
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Târgu Mures
country: Romania
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Novi Sad
country: Serbia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Bratislava
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Durban
country: South Africa
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Poltava
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Zaporizhzhia
country: Ukraine
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
city: Stoke on Trent
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Gold R, Arnold DL, Bar-Or A, Fox RJ, Kappos L, Chen C, Parks B, Miller C. Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years' follow-up of DEFINE, CONFIRM, and ENDORSE. Ther Adv Neurol Disord. 2020 May 12;13:1756286420915005. doi: 10.1177/1756286420915005. eCollection 2020.
citation: Mehta D, Miller C, Arnold DL, Bame E, Bar-Or A, Gold R, Hanna J, Kappos L, Liu S, Matta A, Phillips JT, Robertson D, von Hehn CA, Campbell J, Spach K, Yang L, Fox RJ. Effect of dimethyl fumarate on lymphocytes in RRMS: Implications for clinical practice. Neurology. 2019 Apr 9;92(15):e1724-e1738. doi: 10.1212/WNL.0000000000007262. Epub 2019 Mar 27.
citation: Gold R, Giovannoni G, Phillips JT, Fox RJ, Zhang A, Marantz JL. Sustained Effect of Delayed-Release Dimethyl Fumarate in Newly Diagnosed Patients with Relapsing-Remitting Multiple Sclerosis: 6-Year Interim Results From an Extension of the DEFINE and CONFIRM Studies. Neurol Ther. 2016 Jun;5(1):45-57. doi: 10.1007/s40120-016-0042-8. Epub 2016 Mar 1.