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

Abstract

Objective: To evaluate the safety, tolerability, and efficacy of glatiramer acetate (GA) 40mg 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 20mg (n = 586) or 40mg (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 20mg group, 0.35 for the 40mg 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 40mg dose compared with 20mg dose. Both doses were well‐tolerated with a safety profile similar to that observed in previous studies of 20mg GA. Interpretation: In relapsing‐remitting MS patients, both the currently‐approved GA 20mg and 40mg doses were safe and well‐tolerated, with no gain in efficacy for the higher dose. Ann Neurol 2011;69:75–82.