A phase 3 trial to assess the efficacy and safety of glatiramer acetate injections 40mg administered 3 times a week compared to placebo

BACKGROUND: Glatiramer acetate (GA) is approved worldwide for the treatment of relapsing remitting multiple sclerosis (RRMS). It is administered daily as a 20 mg subcutaneous (SC) 1 ml injection. There has been considerable interest in further investigating the dosing regimen of GA while maintaining efficacy and safety. The Glatiramer Acetate Low Frequency Administration Study (GALA), a multinational randomized placebo-controlled phase 3 trial was conducted to investigate the efficacy and safety of GA 40 mg 1 ml SC injection, administered three times a week. OBJECTIVE: To assess the efficacy, safety and tolerability of GA at 40mg/1ml 3 times a week compared to placebo in a double-blind design. METHODS: RRMS patients (N=1404) were randomized in a 2:1 ratio to receive GA (n=943) 40mg/1ml 3 times a week SC injection or matched placebo (n=461) for 12 months. Patients underwent neurological examinations at screening, baseline, 1,3,6,9, and 12 months or until discontinuation. Brain MRI scans were obtained at months 0, 6, and 12. Annualized relapse rate (ARR) was the primary endpoint and the secondary endpoints included MRI markers; cumulative number of new/enlarging T2 lesions measured at months 6 and 12, cumulative number of gadolinium enhancing (GdE) lesions measured at months 6 and 12 and the percent of brain volume change from baseline to month 12, using SIENA. RESULTS: 8.9% GA and 6.7% placebo patients discontinued from the study. There were no significant differences between the two groups at baseline. However, both cohorts had pronounced T2 lesion load at study entry (19.7 ml ± 20.7 and 17.4 ml ± 17.4 for GA and placebo groups, respectively). Compared to placebo, the ARR was reduced by 34.4 % in the GA group (p <0.0001). A significant reduction also occurred in the cumulative number of new/enlarging T2 lesions (34.4% reduction, p<0.0001) and in cumulative number of GdE lesions (44.8% reduction, p<0.0001) for GA patients. At 12 months, there was no significant difference in percent change of brain volume between GA and placebo (adjusted means (SE) of -0.706 (0.037) vs -0.645 (0.047)). CONCLUSIONS: Glatiramer acetate at 40mg TIW significantly reduced the ARR as well as new/enlarging T2 and GdE lesions. It provides a potential alternative therapeutic option of using a higher dose of GA at a reduced injection frequency. Further pre-planned follow-up beyond 12 months is continuing in an open-label fashion.