A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS

Objective: To evaluate the efficacy and safety of MBP8298 in subjects with secondary progressive multiple sclerosis (SPMS) who express human leukocyte antigen (HLA) haplotype DR2 or DR4 (DR2+ or DR4+). Methods: This multicenter randomized 2-year, double-blind, placebo-controlled study included 612 subjects with a diagnosis of SPMS and an Expanded Disability Status Scale (EDSS) score of 3.5–6.5, stratified according to baseline EDSS score (3.5–5.0, or 5.5–6.5) and HLA haplotype (DR2+ or DR4+, or DR2−/DR4−). Upon entry of 100 DR2−/DR4− subjects, further study enrollment was limited to DR2+ or DR4+ subjects. Subjects were randomly assigned to either 500 mg MBP8298 or placebo, given by IV injection once every 6 months for 2 years. The primary outcome measure was time to progression by ≥1.0 EDSS point (or 0.5 point if baseline EDSS was 5.5 or higher), confirmed 6 months later. Secondary outcomes included mean change in EDSS, mean change in Multiple Sclerosis Functional Composite, MRI changes, annualized relapse rate, and quality of life. Results: There were no significant differences between treatment groups in either the primary or secondary endpoints. MBP8298 was well tolerated in all treated subjects with no safety issues identified. Conclusion: In the population studied, treatment with MBP8298 did not provide a clinical benefit compared to placebo. Classification of evidence: This study provides Class 1 evidence that MBP8298 is not effective in patients with SPMS who are HLA DR2+ or DR4+.