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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00420212
First received: January 8, 2007
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Relapsing-Remitting Multiple Sclerosis
Drug: BG00012
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • Proportion of Subjects Relapsed [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of New or Newly Enlarging T2 Hyperintense Lesions [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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

  • Number of Gadolinium-enhancing T1-weighted Lesions [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Gadolinium (Gd)-Enhancing Lesions [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Note: This outcome measure represents the categorical analysis for the previously listed secondary outcome measure "Number of Gadolinium-enhancing T1-weighted lesions"

  • Annualized Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.

  • Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 1234
Study Start Date: January 2007
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Participants received two placebo capsules orally three times daily (TID)
Drug: Placebo
Experimental: BG00012 240 mg Twice Daily (BID)
Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Drug: BG00012
Other Names:
  • dimethyl fumarate
  • Tecfidera®
Experimental: BG00012 240 mg 3 Times Daily (TID)
Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Drug: BG00012
Other Names:
  • dimethyl fumarate
  • Tecfidera®

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00420212

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Sponsors and Collaborators
Biogen Idec
Investigators
Study Director: Medical Director Biogen Idec
  More Information

No publications provided by Biogen Idec

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00420212     History of Changes
Other Study ID Numbers: 109MS301
Study First Received: January 8, 2007
Results First Received: May 5, 2014
Last Updated: May 5, 2014
Health Authority: Romania: National Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Ukraine: State Pharmacological Center - Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Mexico: Federal Commission for Protection Against Health Risks
Guatemala: Ministry of Public Health and Social Assistance
Australia: Department of Health and Ageing Therapeutic Goods Administration
India: Ministry of Health
South Africa: Department of Health
United States: Institutional Review Board
Austria: Agency for Health and Food Safety
New Zealand: Medsafe
Czech Republic: State Institute for Drug Control
Greece: National Organization of Medicines
Sweden: Medical Products Agency
Slovakia: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Croatia: Ministry of Health and Social Care
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Israel: Ethics Commission
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by Biogen Idec:
relapsing
oral
remitting
multiple sclerosis

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Dimethyl fumarate
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 20, 2014