Phase III dose-comparison study of glatiramer acetate for multiple sclerosis

OBJECTIVE: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40 mg compared to a 20mg dose. METHODS: Patients with multiple sclerosis (MS) with ≥ 1 documented relapse in 12 months prior to screening, or ≥ 2 documented relapses in 24 months prior to screening, and Expanded Disability Status Scale (EDSS) score 0 to 5.5 were enrolled. Patients were evaluated at screening, baseline, and at months 1, 2, 3, 6, 9, and 12. Primary endpoint was rate of confirmed relapses observed during 12-month study. Analysis was by intent-to-treat. RESULTS: A total of 1,155 patients randomized to GA 20 mg (n = 586) or 40 mg (n = 569). The groups were well-matched at baseline on demographic, clinical, and magnetic resonance imaging (MRI) characteristics. The primary endpoint was similar in both groups (relative risk [RR] = 1.07; 95% confidence interval [CI], 0.88-1.31; p = 0.486) with mean annualized relapse rates (ARRs) of 0.33 for the 20 mg group, 0.35 for the 40 mg group, and 0.27 for patients from both groups who completed the entire 1-year treatment. A total of 77% of patients remained relapse-free in both groups. Both groups showed a reduction in mean number of gadolinium-enhancing and new T2 lesions over time with trend for faster reduction in the first trimester with the 40 mg dose compared with 20 mg dose. Both doses were well-tolerated with a safety profile similar to that observed in previous studies of 20 mg GA. INTERPRETATION: In relapsing-remitting MS patients, both the currently-approved GA 20 mg and 40 mg doses were safe and well-tolerated, with no gain in efficacy for the higher dose.