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
Results First Received: May 5, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Relapsing-Remitting Multiple Sclerosis
Interventions: Drug: BG00012
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were screened and enrolled at 198 investigational sites in 28 countries.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
From screening, 1237 eligible subjects were equally randomized. Of these, 1234 subjects received at least one dose of study treatment and comprised the intent-to-treat (ITT) and safety populations.

Reporting Groups
  Description
Placebo Participants received two placebo capsules orally three times daily (TID)
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)
BG00012 240 mg 3 Times Daily (TID) Participants received two 120 mg BG00012 capsules orally three times daily (TID)

Participant Flow:   Overall Study
    Placebo     BG00012 240 mg Twice Daily (BID)     BG00012 240 mg 3 Times Daily (TID)  
STARTED     408 [1]   410 [2]   416 [3]
COMPLETED     317     315     320  
NOT COMPLETED     91     95     96  
Adverse Event                 22                 40                 36  
Lost to Follow-up                 9                 11                 11  
Withdrawal by Subject                 31                 22                 19  
Physician Decision                 4                 4                 3  
Protocol Violation                 4                 4                 8  
Death                 0                 0                 1  
Other-Unspecified                 21                 14                 18  
[1] 408 participants were dosed; 410 participants were randomized
[2] 410 participants were dosed; 411 participants were randomized
[3] 416 participants were dosed; 416 participants were randomized



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Placebo Participants received two placebo capsules orally three times daily (TID)
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)
BG00012 240 mg 3 Times Daily (TID) Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Total Total of all reporting groups

Baseline Measures
    Placebo     BG00012 240 mg Twice Daily (BID)     BG00012 240 mg 3 Times Daily (TID)     Total  
Number of Participants  
[units: participants]
  408     410     416     1234  
Age  
[units: Years]
Mean ± Standard Deviation
  38.5  ± 9.14     38.1  ± 9.11     38.8  ± 8.85     38.5  ± 9.03  
Gender  
[units: Participants]
       
Female     306     296     306     908  
Male     102     114     110     326  
Mean Expanded Disability Status Scale (EDSS) score  
[units: EDSS score]
Mean ± Standard Deviation
  2.48  ± 1.241     2.40  ± 1.290     2.36  ± 1.188     2.42  ± 1.240  
Mean number of relapses within the previous 3 years  
[units: Number of relapses]
Mean ± Standard Deviation
  2.5  ± 1.56     2.5  ± 1.44     2.4  ± 1.27     2.5  ± 1.43  
Mean number of relapses within the past 12 months  
[units: Number of relapses]
Mean ± Standard Deviation
  1.3  ± 0.67     1.3  ± 0.67     1.3  ± 0.60     1.3  ± 0.65  
Time since first multiple sclerosis (MS) diagnosis  
[units: Years]
Mean ± Standard Deviation
  5.8  ± 5.78     5.6  ± 5.39     5.1  ± 5.29     5.5  ± 5.49  
Mean number of gadolinium (Gd) enhancing lesions [1]
[units: Number of Gd enhancing lesions]
Mean ± Standard Deviation
  1.6  ± 3.45     1.2  ± 3.30     1.2  ± 4.10     1.4  ± 3.64  
[1] This baseline measure could only be assessed in the magnetic resonance imaging (MRI) cohort. The MRI cohort included 540 intent-to-treat (ITT) subjects who were enrolled at sites that participated in the MRI portion of the study and who had MRI data (180 placebo, 176 BG00012 BID, 184 BG00012 TID). Sites could participate only if their MRI capability was validated by the independent MRI reading center. Approximately 95% of all subjects enrolled at MRI sites participated in the MRI portion of the study.



  Outcome Measures
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1.  Primary:   Proportion of Subjects Relapsed   [ Time Frame: 2 years ]

2.  Secondary:   Number of New or Newly Enlarging T2 Hyperintense Lesions   [ Time Frame: 2 years ]

3.  Secondary:   Number of Gadolinium-enhancing T1-weighted Lesions   [ Time Frame: 2 years ]

4.  Secondary:   Number of Subjects With Gadolinium (Gd)-Enhancing Lesions   [ Time Frame: 2 years ]

5.  Secondary:   Annualized Relapse Rate   [ Time Frame: 2 years ]

6.  Secondary:   Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)   [ Time Frame: 2 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Biogen Idec Study Medical Director
Organization: Biogen Idec
e-mail: clinicaltrials@biogenidec.com


No publications provided by Biogen Idec

Publications automatically indexed to this study:

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