Efficacy and Safety Study of Oral BG00012 With Active Reference in Relapsing-Remitting Multiple Sclerosis (CONFIRM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00451451
First received: March 21, 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
Drug: Glatiramer Acetate

  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 randomized at 205 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, 1430 eligible subjects were equally randomized. Of these, 1417 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)
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD) Participants received glatiramer acetate (GA) 20 mg subcutaneous injection once daily (QD)

Participant Flow:   Overall Study
    Placebo     BG00012 240 mg Twice Daily (BID)     BG00012 240 mg 3 Times Daily (TID)     Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)  
STARTED     363 [1]   359 [2]   345 [3]   350 [4]
COMPLETED     278     284     273     292  
NOT COMPLETED     85     75     72     58  
Adverse Event                 11                 21                 26                 10  
Lost to Follow-up                 11                 9                 8                 11  
Consent Withdrawn                 14                 9                 17                 17  
Investigator Decision                 6                 2                 1                 2  
Subject Non-Compliance                 8                 4                 3                 3  
Death                 1                 0                 0                 1  
Other Reasons for Not Completing Study                 34                 30                 17                 14  
[1] 363 participants were dosed; 363 participants were randomized
[2] 359 participants were dosed; 362 participants were randomized
[3] 345 participants were dosed; 345 participants were randomized
[4] 350 participants were dosed; 360 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.
No text entered.

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)
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD) Participants received glatiramer acetate (GA) 20 mg subcutaneous injection once daily (QD)
Total Total of all reporting groups

Baseline Measures
    Placebo     BG00012 240 mg Twice Daily (BID)     BG00012 240 mg 3 Times Daily (TID)     Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)     Total  
Number of Participants  
[units: participants]
  363     359     345     350     1417  
Age  
[units: Years]
Mean ± Standard Deviation
  36.9  ± 9.24     37.8  ± 9.35     37.8  ± 9.39     36.7  ± 9.06     37.3  ± 9.26  
Gender  
[units: Participants]
         
Female     251     245     250     247     993  
Male     112     114     95     103     424  
Mean Expanded Disability Status Scale (EDSS) score  
[units: EDSS score]
Mean ± Standard Deviation
  2.59  ± 1.170     2.56  ± 1.202     2.52  ± 1.185     2.57  ± 1.223     2.56  ± 1.194  
Mean number of relapses within the previous 3 years  
[units: Number of relapses]
Mean ± Standard Deviation
  2.5  ± 1.46     2.4  ± 1.27     2.6  ± 1.50     2.4  ± 1.32     2.5  ± 1.39  
Mean number of relapses within the past 12 months  
[units: Number of relapses]
Mean ± Standard Deviation
  1.4  ± 0.80     1.3  ± 0.63     1.4  ± 0.72     1.4  ± 0.64     1.4  ± 0.70  
Time since first multiple sclerosis (MS) diagnosis  
[units: years]
Mean ± Standard Deviation
  4.8  ± 5.01     4.9  ± 5.11     4.6  ± 5.23     4.4  ± 4.70     4.7  ± 5.01  
Mean number of Gadolinium(Gd)-enhancing T1-weighted lesions [1]
[units: Number of Gd enhancing lesions]
Mean ± Standard Deviation
  2.7  ± 7.71     2.7  ± 6.22     1.9  ± 5.02     2.4  ± 6.81     2.4  ± 6.51  
[1] This baseline measure could only be assessed in the magnetic resonance imaging (MRI) cohort. The MRI cohort included 681 intent-to-treat (ITT) subjects who were enrolled at sites that participated in the MRI portion of the study and who had MRI data (167 placebo, 169 BG00012 BID, 170 BG00012 TID, and 175 GA). 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:   Annualized Relapse Rate   [ Time Frame: 2 years ]

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

3.  Secondary:   Number of New T1 Hypointense Lesions   [ Time Frame: 2 years ]

4.  Secondary:   Proportion of Subjects Relapsed   [ Time Frame: 2 years ]

5.  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
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Time Frame 2 years
Additional Description The safety population consisted of all subjects who received at least 1 dose of study treatment. Safety data were analyzed by actual treatment received. One patient randomly assigned to the BG00012 TID group & included in the group of the ITT population took GA throughout the study and was therefore counted in the GA group of the safety population.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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 BG00012 Combined BG00012 240 mg twice daily (BID) dose group and BG00012 240 mg 3 times daily (TID) dose group
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD) Participants received glatiramer acetate (GA) 20 mg subcutaneous injection once daily (QD)

Other Adverse Events
    Placebo     BG00012 240 mg Twice Daily (BID)     BG00012 240 mg 3 Times Daily (TID)     Total BG00012     Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)  
Total, other (not including serious) adverse events            
# participants affected / at risk     332/363     336/359     316/344     652/703     303/351  
Ear and labyrinth disorders            
VERTIGO † 1          
# participants affected / at risk     22/363 (6.06%)     9/359 (2.51%)     13/344 (3.78%)     22/703 (3.13%)     15/351 (4.27%)  
Gastrointestinal disorders            
DIARRHEA † 1          
# participants affected / at risk     28/363 (7.71%)     45/359 (12.53%)     50/344 (14.53%)     95/703 (13.51%)     14/351 (3.99%)  
NAUSEA † 1          
# participants affected / at risk     29/363 (7.99%)     40/359 (11.14%)     51/344 (14.83%)     91/703 (12.94%)     15/351 (4.27%)  
ABDOMINAL PAIN UPPER † 1          
# participants affected / at risk     17/363 (4.68%)     36/359 (10.03%)     33/344 (9.59%)     69/703 (9.82%)     4/351 (1.14%)  
ABDOMINAL PAIN † 1          
# participants affected / at risk     15/363 (4.13%)     25/359 (6.96%)     26/344 (7.56%)     51/703 (7.25%)     4/351 (1.14%)  
VOMITING † 1          
# participants affected / at risk     12/363 (3.31%)     25/359 (6.96%)     23/344 (6.69%)     48/703 (6.83%)     8/351 (2.28%)  
DYSPEPSIA † 1          
# participants affected / at risk     8/363 (2.20%)     12/359 (3.34%)     16/344 (4.65%)     28/703 (3.98%)     6/351 (1.71%)  
General disorders            
FATIGUE † 1          
# participants affected / at risk     33/363 (9.09%)     37/359 (10.31%)     33/344 (9.59%)     70/703 (9.96%)     30/351 (8.55%)  
PYREXIA † 1          
# participants affected / at risk     19/363 (5.23%)     11/359 (3.06%)     24/344 (6.98%)     35/703 (4.98%)     17/351 (4.84%)  
INJECTION SITE ERYTHEMA † 1          
# participants affected / at risk     0/363 (0.00%)     0/359 (0.00%)     0/344 (0.00%)     0/703 (0.00%)     31/351 (8.83%)  
INJECTION SITE PAIN † 1          
# participants affected / at risk     0/363 (0.00%)     0/359 (0.00%)     0/344 (0.00%)     0/703 (0.00%)     29/351 (8.26%)  
Infections and infestations            
NASOPHARYNGITIS † 1          
# participants affected / at risk     58/363 (15.98%)     62/359 (17.27%)     63/344 (18.31%)     125/703 (17.78%)     51/351 (14.53%)  
URINARY TRACT INFECTION † 1          
# participants affected / at risk     42/363 (11.57%)     51/359 (14.21%)     40/344 (11.63%)     91/703 (12.94%)     46/351 (13.11%)  
UPPER RESPIRATORY TRACT INFECTION † 1          
# participants affected / at risk     34/363 (9.37%)     36/359 (10.03%)     47/344 (13.66%)     83/703 (11.81%)     27/351 (7.69%)  
INFLUENZA † 1          
# participants affected / at risk     22/363 (6.06%)     20/359 (5.57%)     25/344 (7.27%)     45/703 (6.40%)     15/351 (4.27%)  
BRONCHITIS † 1          
# participants affected / at risk     14/363 (3.86%)     14/359 (3.90%)     22/344 (6.40%)     36/703 (5.12%)     16/351 (4.56%)  
SINUSITIS † 1          
# participants affected / at risk     11/363 (3.03%)     18/359 (5.01%)     18/344 (5.23%)     36/703 (5.12%)     11/351 (3.13%)  
Investigations            
ALANINE AMINOTRANSFERASE INCREASED † 1          
# participants affected / at risk     25/363 (6.89%)     16/359 (4.46%)     22/344 (6.40%)     38/703 (5.41%)     20/351 (5.70%)  
ALBUMIN URINE PRESENT † 1          
# participants affected / at risk     15/363 (4.13%)     22/359 (6.13%)     14/344 (4.07%)     36/703 (5.12%)     18/351 (5.13%)  
PROTEIN URINE PRESENT † 1          
# participants affected / at risk     10/363 (2.75%)     18/359 (5.01%)     7/344 (2.03%)     25/703 (3.56%)     15/351 (4.27%)  
Musculoskeletal and connective tissue disorders            
BACK PAIN † 1          
# participants affected / at risk     33/363 (9.09%)     34/359 (9.47%)     36/344 (10.47%)     70/703 (9.96%)     32/351 (9.12%)  
ARTHRALGIA † 1          
# participants affected / at risk     26/363 (7.16%)     20/359 (5.57%)     27/344 (7.85%)     47/703 (6.69%)     17/351 (4.84%)  
PAIN IN EXTREMITY † 1          
# participants affected / at risk     29/363 (7.99%)     21/359 (5.85%)     26/344 (7.56%)     47/703 (6.69%)     21/351 (5.98%)  
MUSCLE SPASMS † 1          
# participants affected / at risk     14/363 (3.86%)     13/359 (3.62%)     21/344 (6.10%)     34/703 (4.84%)     8/351 (2.28%)  
Nervous system disorders            
MULTIPLE SCLEROSIS RELAPSE † 1          
# participants affected / at risk     147/363 (40.50%)     104/359 (28.97%)     81/344 (23.55%)     185/703 (26.32%)     115/351 (32.76%)  
HEADACHE † 1          
# participants affected / at risk     49/363 (13.50%)     52/359 (14.48%)     46/344 (13.37%)     98/703 (13.94%)     46/351 (13.11%)  
PARAESTHESIA † 1          
# participants affected / at risk     31/363 (8.54%)     21/359 (5.85%)     21/344 (6.10%)     42/703 (5.97%)     15/351 (4.27%)  
HYPOAESTHESIA † 1          
# participants affected / at risk     21/363 (5.79%)     11/359 (3.06%)     19/344 (5.52%)     30/703 (4.27%)     16/351 (4.56%)  
Psychiatric disorders            
DEPRESSION † 1          
# participants affected / at risk     35/363 (9.64%)     24/359 (6.69%)     15/344 (4.36%)     39/703 (5.55%)     28/351 (7.98%)  
INSOMNIA † 1          
# participants affected / at risk     18/363 (4.96%)     15/359 (4.18%)     10/344 (2.91%)     25/703 (3.56%)     13/351 (3.70%)  
Renal and urinary disorders            
PROTEINURIA † 1          
# participants affected / at risk     25/363 (6.89%)     29/359 (8.08%)     35/344 (10.17%)     64/703 (9.10%)     30/351 (8.55%)  
MICROALBUMINURIA † 1          
# participants affected / at risk     13/363 (3.58%)     14/359 (3.90%)     19/344 (5.52%)     33/703 (4.69%)     15/351 (4.27%)  
Respiratory, thoracic and mediastinal disorders            
COUGH † 1          
# participants affected / at risk     17/363 (4.68%)     16/359 (4.46%)     18/344 (5.23%)     34/703 (4.84%)     9/351 (2.56%)  
OROPHARYNGEAL PAIN † 1          
# participants affected / at risk     14/363 (3.86%)     12/359 (3.34%)     21/344 (6.10%)     33/703 (4.69%)     15/351 (4.27%)  
Skin and subcutaneous tissue disorders            
RASH † 1          
# participants affected / at risk     13/363 (3.58%)     24/359 (6.69%)     28/344 (8.14%)     52/703 (7.40%)     8/351 (2.28%)  
PRURITIS † 1          
# participants affected / at risk     11/363 (3.03%)     20/359 (5.57%)     24/344 (6.98%)     44/703 (6.26%)     7/351 (1.99%)  
ERYTHEMA † 1          
# participants affected / at risk     5/363 (1.38%)     16/359 (4.46%)     21/344 (6.10%)     37/703 (5.26%)     6/351 (1.71%)  
Vascular disorders            
FLUSHING † 1          
# participants affected / at risk     13/363 (3.58%)     110/359 (30.64%)     83/344 (24.13%)     193/703 (27.45%)     6/351 (1.71%)  
HOT FLUSH † 1          
# participants affected / at risk     8/363 (2.20%)     18/359 (5.01%)     19/344 (5.52%)     37/703 (5.26%)     4/351 (1.14%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (13.1)



  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


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Responsible Party: Biogen Idec
ClinicalTrials.gov Identifier: NCT00451451     History of Changes
Other Study ID Numbers: 109MS302
Study First Received: March 21, 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
Ireland: Irish Medicines Board
Mexico: Federal Commission for Protection Against Health Risks
Bulgaria: Ministry of Health
Spain: Spanish Agency of Medicines
Estonia: The State Agency of Medicine
United States: Institutional Review Board
New Zealand: Medsafe
Czech Republic: State Institute for Drug Control
Greece: National Organization of Medicines
Slovakia: State Institute for Drug Control
Germany: Federal Institute for Drugs and Medical Devices
Croatia: Ministry of Health and Social Care
Canada: Health Canada
Latvia: State Agency of Medicines
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