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

Phase 3

Completed

Conditions: Relapsing-Remitting Multiple Sclerosis

Interventions: Drug: BG00012
Drug: Glatiramer Acetate
Drug: Placebo

Registration Number: NCT00451451

Lead Sponsor: Biogen

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1417

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BG00012 240 mg Twice Daily (BID)	Placebo	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)	BG00012	Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Glatiramer Acetate (GA) 20 mg Injection Once Daily (QD)	Glatiramer Acetate	Participants received glatiramer acetate (GA) 20 mg subcutaneous injection once daily (QD)
Placebo	Placebo	Participants received two placebo capsules orally three times daily (TID)
BG00012 240 mg Twice Daily (BID)	BG00012	Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)

Primary Outcome Measures

Name	Time	Method
Annualized Relapse Rate	2 years	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.

Secondary Outcome Measures

Name	Time	Method
Number of New T1 Hypointense Lesions	2 years	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.
Number of New or Newly Enlarging T2 Hyperintense Lesions	2 years	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.
Proportion of Subjects Relapsed	2 years	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.
Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)	2 years	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