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

Study Overview
=================
Brief Summary
-----------------
To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time period. Other goals of the study are 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 MS to get worse. Other objectives of the study are to determine the safety and tolerability of BG00012, as well as the effect it may have on tests and evaluations used to assess MS. Additionally, glatiramer acetate is being used to compare its benefits and risks with placebo and BG00012.

Detailed Description
-----------------
Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects approximately 400,000 persons in North America and 365,000 persons in Europe. It is predominantly a disease of young adults, primarily women, with disease onset typically occurring between the ages of 20 and 40.

Official Title
-----------------
A Randomized, Multicenter, Placebo-Controlled and Active Reference (Glatiramer Acetate) Comparison Study to Evaluate the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis

Conditions
-----------------
Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
-----------------
* Drug: BG00012
* Drug: Placebo
* Drug: Glatiramer Acetate


Participation Criteria
=================
Eligibility 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: Key Inclusion Criteria: Must have 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: Other chronic disease of immune system, malignancies, urologic, pulmonary, gastrointestinal disease Pregnant or nursing women Note: Other protocol-defined inclusion/exclusion criteria may apply.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 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®;Drug: Placebo<br> <br> |
| 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®;|
| Placebo Comparator: Placebo<br>Participants received two placebo capsules orally three times daily (TID) | Drug: Placebo<br> <br> |
| Active Comparator: Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)<br>Participants received glatiramer acetate (GA) 20 mg subcutaneous injection once daily (QD) | Drug: Glatiramer Acetate<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Expanded Disability Status Scale (EDSS ) score(≤2.0 versus>2.0), age (<40 versus ≥40 years), region, and the number of relapses in the 1 year prior to enrollment. | 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 hyperintense lesion count were calculated from a negative binomial regression model adjusted for region and baseline T2 hyperintense lesion volume. | 2 years | 
| Number of New T1 Hypointense Lesions | The number of new T1 hypointense lesions at 2 years that developed in each subject compared to baseline assessed on brain magnetic resonance imaging (MRI) scans. The estimates of mean T1 hypointense lesion count were calculated from a negative binomial regression model adjusted for region and baseline T1 hypointense lesion volume. | 2 years | 
| 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 neurologic 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 | 
| Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS) | EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. 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 ≥1.5 point increase in subjects with a baseline EDSS=0, and required that the increase from baseline was confirmed ≥ 12weeks 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
relapsing, multiple sclerosis, oral, remitting