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Relapsing-Remitting Multiple SclerosisPhase 3DEFINENCT00420212

Efficacy and Safety of Oral BG00012 in Relapsing-Remitting Multiple Sclerosis

A Phase 3 study testing BG00012 in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 159 sites in 29 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time period. To determine if, over time, BG00012 treatment can decrease the number of certain types of brain lesions commonly seen in MS patients and slow down the time it takes for the disease to get worse. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Relapsing-Remitting Multiple Sclerosis
What is being tested?
BG00012
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,234 participants
Where
159 sitesin 29 countries
Study dates
Jan 2007to Feb 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the randomization:
  • Must have a confirmed diagnosis of RRMS according to McDonald criteria #1-4.
  • Must have a baseline EDSS between 0.0 and 5.0, inclusive.
  • Must have relapsing-remitting disease course.

Who cannot join

  • Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at randomization:
  • 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.

Trial locations and contacts

159 sites in 29 countries.

159 sites in 29 countries

United States39 sites
  • Research Site

    Albany, New York

  • Research Site

    Atlanta, Georgia

  • Research Site

    Brighton, Massachusetts

  • Research Site

    Columbia, Missouri

  • Research Site

    Dayton, Ohio

  • Research Site

    Des Moines, Iowa

  • Research Site

    East Providence, Rhode Island

  • Research Site

    Erie, Pennsylvania

  • Research Site

    Evanston, Illinois

  • Research Site

    Farmington Hills, Michigan

  • Research Site

    Fort Wayne, Indiana

  • Research Site

    Gilbert, Arizona

  • Research Site

    Henderson, Nevada

  • Research Site

    Hershey, Pennsylvania

  • Research Site

    Hopedale, Massachusetts

  • Research Site

    Indianapolis, Indiana

  • Research Site

    Las Vegas, Nevada

  • Research Site

    Lebanon, New Hampshire

  • Research Site

    Lexington, Kentucky

  • Research Site

    Lexington, Massachusetts

  • Research Site

    Minneapolis, Minnesota

  • Research Site

    New Haven, Connecticut

  • Research Site

    Newport News, Virginia

  • Research Site

    Palos Heights, Illinois

  • Research Site

    Phoenix, Arizona

  • Research Site

    Pittsburgh, Pennsylvania

  • Research Site

    Providence, Rhode Island

  • Research Site

    Raleigh, North Carolina

  • Research Site

    San Antonio, Texas

  • Research Site

    San Francisco, California

  • Research Site

    Seattle, Washington

  • Research Site

    Springfield, Massachusetts

  • Research Site

    St Louis, Missouri

  • Research Site

    Staten Island, New York

  • Research Site

    Vero Beach, Florida

  • Research Site

    Washington D.C., District of Columbia

  • Research Site

    Wichita, Kansas

  • Research Site

    Wien, Virginia

  • Research Site

    Worcester, Massachusetts

Other trials in United States

Germany15 sites
  • Research Site

    Bad Neustadt-Saale

  • Research Site

    Berlin

  • Research Site

    Bochum

  • Research Site

    Düsseldorf

  • Research Site

    Essen

  • Research Site

    Gieben

  • Research Site

    Halle

  • Research Site

    Hamburg

  • Research Site

    Hanover

  • Research Site

    Leipzig

  • Research Site

    Minden

  • Research Site

    München

  • Research Site

    Münster

  • Research Site

    Osnabrück

  • Research Site

    Westerstede

Other trials in Germany

India10 sites
  • Research Site

    Chenna

  • Research Site

    Coimbatore

  • Research Site

    Delhi

  • Research Site

    Hyderabad

  • Research Site

    Kolkata

  • Research Site

    Lucknow

  • Research Site

    Mangalore

  • Research Site

    Mumbai

  • Research Site

    New Delhi

  • Research Site

    Pune

Other trials in India

Australia9 sites
  • Research Site

    Camperdown, New South Wales

  • Research Site

    Chatswood, New South Wales

  • Research Site

    Fitzroy

  • Research Site

    Geelong

  • Research Site

    Heidelberg

  • Research Site

    Kogarah

  • Research Site

    Liverpool

  • Research Site

    Melbourne

  • Research Site

    Newcastle

Other trials in Australia

Belgium8 sites
  • Research Site

    Antwerp

  • Research Site

    Bruges

  • Research Site

    Charleroi

  • Research Site

    Diepenbeek

  • Research Site

    Leuven

  • Research Site

    Lommel

  • Research Site

    Sijsele-Damme

  • Research Site

    Woluwe

Other trials in Belgium

Canada7 sites
  • Research Site

    Burnaby, British Columbia

  • Research Site

    Halifax, Nova Scotia

  • Research Site

    Lévis, Quebec

  • Research Site

    Montreal

  • Research Site

    Ottawa, Ontario

  • Research Site

    Québec, Quebec

  • Research Site

    Regina, Saskatchewan

Other trials in Canada

Czechia7 sites
  • Research Site

    Brno

  • Research Site

    Jihlava

  • Research Site

    Opava

  • Research Site

    Ostrava

  • Research Site

    Pilsen

  • Research Site

    Prague

  • Research Site

    Teplice

Other trials in Czechia

Poland7 sites
  • Research Site

    Bialystok

  • Research Site

    Gdansk

  • Research Site

    Katowice

  • Research Site

    Krakow

  • Research Site

    Poznan

  • Research Site

    Szczecin

  • Research Site

    Warsaw

Other trials in Poland

Ukraine6 sites
  • Research Site

    Kharkiv

  • Research Site

    Kyiv

  • Research Site

    Lviv

  • Research Site

    Odesa

  • Research Site

    Poltava

  • Research Site

    Zaporizhzhya

Other trials in Ukraine

United Kingdom5 sites
  • Research Site

    London

  • Research Site

    Newcastle

  • Research Site

    Oxford

  • Research Site

    Sheffield

  • Research Site

    Staffordshire

Other trials in United Kingdom

Austria4 sites
  • Research Site

    Graz

  • Research Site

    Innsbruck

  • Research Site

    Linz

  • Research Site

    Vienna, State of Vienna

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France4 sites
  • Research Site

    Clermont-Ferrand

  • Research Site

    Nice

  • Research Site

    Paris

  • Research Site

    Rennes

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Israel4 sites
  • Research Site

    Ashkelon

  • Research Site

    Beer Yaakov

  • Research Site

    Jerusalem

  • Research Site

    Tel HaShomer

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Serbia4 sites
  • Research Site

    Belgrade

  • Research Site

    Kragujevac

  • Research Site

    Niš

  • Research Site

    Novi Sad

Other trials in Serbia

Greece3 sites
  • Research Site

    Athens

  • Research Site

    Ioannina

  • Research Site

    Thessaloniki

Other trials in Greece

Mexico3 sites
  • Research Site

    Guadalajara

  • Research Site

    Mexico City

  • Research Site

    San Luis Potosí City

Other trials in Mexico

New Zealand3 sites
  • Research Site

    Christchurch

  • Research Site

    Grafton

  • Research Site

    Hamilton

Other trials in New Zealand

Romania3 sites
  • Research Site

    Bucharest

  • Research Site

    Cluj-Napoca

  • Research Site

    Timișoara

Other trials in Romania

Slovakia3 sites
  • Research Site

    Bratislava

  • Research Site

    Košice

  • Research Site

    Martin

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South Africa3 sites
  • Research Site

    Cape Town

  • Research Site

    Durban

  • Research Site

    Rosebank

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Switzerland3 sites
  • Research Site

    Basel

  • Research Site

    Sankt Gallen

  • Research Site

    Zurich

Other trials in Switzerland

Netherlands2 sites
  • Research Site

    Breda

  • Research Site

    Sittard

Other trials in Netherlands

Bosnia and Herzegovina1 site
  • Research Site

    Banja Luka, Republic of Srpksa

Other trials in Bosnia and Herzegovina

Croatia1 site
  • Research Site

    Zagreb

Other trials in Croatia

Guatemala1 site
  • Research Site

    Guatemala City

Other trials in Guatemala

Italy1 site
  • Research Site

    Roma

Other trials in Italy

Moldova1 site
  • Research Site

    Chisinau

Other trials in Moldova

North Macedonia1 site
  • Research Site

    Skopje

Other trials in North Macedonia

Virgin Islands1 site
  • Research Site

    Vienna

About this study

Official title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Comparison Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis

To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time period. To determine if, over time, BG00012 treatment can decrease the number of certain types of brain lesions commonly seen in MS patients and slow down the time it takes for the disease to get worse.

The purpose of this study is also to determine the safety of BG00012 and how well it is tolerated. Another goal is to see what effect BG00012 may have on tests and evaluations used to assess MS.

Being tested
BG00012, Placebo
Keywords
relapsing, oral, remitting, multiple sclerosis
Medical subject headings
Multiple Sclerosis, Relapsing-Remitting, Recurrence, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BG00012Drug

    Also called dimethyl fumarate, Tecfidera®

  • PlaceboDrug

Study groups in NCT00420212
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants received two placebo capsules orally three times daily (TID)
Receives: Drug: Placebo
BG00012 240 mg Twice Daily (BID)ExperimentalParticipants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Receives: Drug: BG00012
BG00012 240 mg 3 Times Daily (TID)ExperimentalParticipants received two 120 mg BG00012 capsules orally three times daily (TID)
Receives: Drug: BG00012

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Subjects Relapsed

    A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurolgic evaluation committee. The proportion of subjects with a relapse was estimated using the Kaplan-Meier method, which was based on the time-to-first-relapse survival distribution.

    Measured: 2 years

Secondary outcomes (5)
  1. Number of New or Newly Enlarging T2 Hyperintense Lesions

    The number of new or newly enlarging T2 hyperintense lesions at 2 years that developed in each subject compared to baseline assessed on brain magnetic resonance imaging (MRI) scans. The estimates of mean T2 lesion count were calculated from a negative binomial regression model adjusted for region and baselineT2 lesion volume

    Measured: 2 years

  2. Number of Gadolinium-enhancing T1-weighted Lesions

    The number of Gd-enhancing lesions was assessed using brain MRI scans following administration of gadolinium, a contrast agent. The mean number of Gd-enhancing lesions at 2 years was the average of the number of lesions at 2 years in a treatment group.

    Measured: 2 years

  3. Number of Subjects With Gadolinium (Gd)-Enhancing Lesions

    Note: This outcome measure represents the categorical analysis for the previously listed secondary outcome measure "Number of Gadolinium-enhancing T1-weighted lesions"

    Measured: 2 years

  4. Annualized Relapse Rate

    A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurologic evaluation committee. The adjusted annualized relapse rate was calculated from a negative binomial regression model, adjusted for baseline EDSS (≤ 2.0 vs. >2.0), age (<40 versus ≥40 years), region, and the number of relapses in the 1 year prior to enrollment.

    Measured: 2 years

  5. Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)

    The EDSS is based on a standardized neurological examination and focuses on symptoms that commonly occur in MS. EDSS scores range from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as ≥ 1.0 point increase in subjects with a baseline EDSS of ≥1.0, or a ≥1.5 point increase in subjects with a baseline EDSS = 0, and required that the increase from baseline was confirmed ≥12 weeks later. The proportion of subjects with confirmed (12-week) disability progression was estimated using the Kaplan-Meier method, which was based on the time-to-first-progression survival distribution.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jan 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionFeb 2011
  4. Study completionFeb 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,234 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00420212
Sponsor's protocol ID
109MS301
Acronym
DEFINE
Status last verified
Jan 2015
First submitted
8 Jan 2007
Last updated
26 Jan 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32426039
  • 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.

    PubMed 30918100
  • Fox RJ, Gold R, Phillips JT, Okwuokenye M, Zhang A, Marantz JL. Efficacy and Tolerability of Delayed-release Dimethyl Fumarate in Black, Hispanic, and Asian Patients with Relapsing-Remitting Multiple Sclerosis: Post Hoc Integrated Analysis of DEFINE and CONFIRM. Neurol Ther. 2017 Dec;6(2):175-187. doi: 10.1007/s40120-017-0077-5. Epub 2017 Aug 2.

    PubMed 28770420
  • Fernandez O, Giovannoni G, Fox RJ, Gold R, Phillips JT, Potts J, Okwuokenye M, Marantz JL. Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM. Clin Ther. 2017 Aug;39(8):1671-1679. doi: 10.1016/j.clinthera.2017.06.012. Epub 2017 Jul 25.

    PubMed 28751099
  • Fox RJ, Chan A, Zhang A, Xiao J, Levison D, Lewin JB, Edwards MR, Marantz JL. Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis. Curr Med Res Opin. 2017 Feb;33(2):175-183. doi: 10.1080/03007995.2016.1248380. Epub 2016 Nov 10.

    PubMed 27733070
  • 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.

    PubMed 26932146
  • Giovannoni G, Gold R, Fox RJ, Kappos L, Kita M, Yang M, Sarda SP, Zhang R, Viglietta V, Havrdova E. Relapses Requiring Intravenous Steroid Use and Multiple-Sclerosis-related Hospitalizations: Integrated Analysis of the Delayed-release Dimethyl Fumarate Phase III Studies. Clin Ther. 2015 Nov 1;37(11):2543-51. doi: 10.1016/j.clinthera.2015.09.011. Epub 2015 Oct 31.

    PubMed 26526385
  • Nakamura K, Brown RA, Narayanan S, Collins DL, Arnold DL; Alzheimer's Disease Neuroimaging Initiative. Diurnal fluctuations in brain volume: Statistical analyses of MRI from large populations. Neuroimage. 2015 Sep;118:126-32. doi: 10.1016/j.neuroimage.2015.05.077. Epub 2015 Jun 3.

    PubMed 26049148
  • Kita M, Fox RJ, Gold R, Giovannoni G, Phillips JT, Sarda SP, Kong J, Viglietta V, Sheikh SI, Okwuokenye M, Kappos L. Effects of delayed-release dimethyl fumarate (DMF) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: an integrated analysis of the phase 3 DEFINE and CONFIRM studies. Clin Ther. 2014 Dec 1;36(12):1958-1971. doi: 10.1016/j.clinthera.2014.08.013. Epub 2014 Oct 12.

    PubMed 25315404
  • Fox RJ, Kita M, Cohan SL, Henson LJ, Zambrano J, Scannevin RH, O'Gorman J, Novas M, Dawson KT, Phillips JT. BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr Med Res Opin. 2014 Feb;30(2):251-62. doi: 10.1185/03007995.2013.849236. Epub 2013 Oct 22.

    PubMed 24131282
  • Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1098-107. doi: 10.1056/NEJMoa1114287.

    PubMed 22992073

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BG00012 in people with Relapsing-Remitting Multiple Sclerosis, run by Biogen at 159 sites in 29 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 159 sites in United States, Germany, India, Australia, Belgium and 24 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Subjects Relapsed (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00420212, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2015.

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