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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: BG00012
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received two placebo capsules orally three times daily (TID) | Drug: Placebo<br> <br> |
| Experimental: BG00012 240 mg Twice Daily (BID)<br>Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD) | Drug: BG00012<br> <br> * Other names: Tecfidera®;|
| Experimental: BG00012 240 mg 3 Times Daily (TID)<br>Participants received two 120 mg BG00012 capsules orally three times daily (TID) | Drug: BG00012<br> <br> * Other names: Tecfidera®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 years | 
| 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. | 2 years | 
| 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 | 2 years | 
| 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. | 2 years | 
| 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. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsing, oral, remitting, multiple sclerosis