Multiple sclerosis 4Tuesday, May 30, 2006, 16:00 - 16:15
Efficacy of a novel oral single-agent fumarate, BG00012, in patients with relapsing-remitting multiple sclerosis: results of a phase 2 studyL. Kappos, D.H. Miller, D.G. MacManus, R. Gold, E. Havrdova, V. Limmroth, C. Polman, K. Schmierer, T. Yousry, M. Yang, M. Eraksoy, E. Meluzinova, I. Rektor, G.N. O'Neill (Basel, CH; London, GB; Gottingen, D; Prague, CZ; Cologne, D; Amsterdam, NL; Cambridge, USA; Istanbul, TR; Brno, CZ)
Objective: To determine the efficacy of three dose levels of BG00012, a novel oral fumarate preparation, on brain lesion activity as measured by magnetic resonance imaging (MRI) in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods: This was a randomised, double-blind, placebo-controlled clinical trial of BG00012 in patients with RRMS. Men and women 18 to 55 years of age were eligible for the study if they had a diagnosis of RRMS and an Expanded Disability Status Scale (EDSS) score between 0.0 and 5.0. In addition, patients must have had either >=1 relapse within 12 months prior to randomisation or gadolinium-enhancing (Gd+) lesions on cranial MRI at screening. Patients were assigned to four treatment groups and received BG00012 capsules 120 mg by mouth (PO) once daily (120 mg/day), 120 mg three times daily (360 mg/day), 240 mg three times daily (720 mg/day), or placebo for 24 weeks. The treatment period was followed by a 24-week dose-blinded safety-extension period during which all patients received BG00012. The primary end point was the total number of Gd+ lesions over four MRI scans at weeks 12, 16, 20, and 24 (calculated as the sum of the four scans). Secondary end points included the cumulative number of new Gd+ lesions from week 4 to week 24 and the number of new/enlarging T2-hyperintense lesions at week 24. Additional end points included the number of new T1-hypointense lesions at week 24, relapse rate, and disability progression as measured by EDSS.
Results: A total of 257 patients were enrolled in the study; 64 patients each were randomly assigned to receive one of the three BG00012 doses and 65 patients to placebo. Approximately 90% of patients completed the 24-week treatment period. BG00012 (720 mg/day) significantly reduced the mean number of new Gd+ lesions (the primary end point) compared with placebo. In addition, BG00012 reduced the cumulative number of new Gd+ lesions, the number of new/enlarging T2-hyperintense lesions, and the number of new T1-hypointense lesions compared with placebo.
Conclusion: BG00012 significantly reduces brain lesion activity, in a dose-dependent manner, as measured by MRI in patients with RRMS over 24 weeks of treatment.