A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS
A phase III study evaluating the efficacy and safety of MBP8298 in secondary progressive MS
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DOI：
10.1212/wnl.0b013e318233b240
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发表时间：
2011-10-01
期刊：
影响因子：
9.9
通讯作者：
Verco, T.
中科院分区：
文献类型：
--
作者：
Freedman, M. S.;Bar-Or, A.;Verco, T.
目的：评估MBP 8298在表达人类白细胞抗原（HLA）单倍型DR 2或DR 4（DR 2（+）或DR 4（+））的继发性进展型多发性硬化（SPMS）受试者中的疗效和安全性。本多中心随机、2年、双盲、安慰剂对照研究包括612名诊断为SPMS且扩展残疾状态量表（EDSS）评分为3.5-6.5的受试者，根据基线EDSS评分（3.5-5.0，或5.5-6.5）和HLA单倍型（DR 2（+）或DR 4（+），或DR 2（-）/DR 4（-））分层。入组100例DR 2（-）/DR 4（-）受试者后，进一步的研究入组仅限于DR 2（+）或DR 4（+）受试者。受试者被随机分配到500 mg MBP 8298或安慰剂组，每6个月静脉注射一次，持续2年。主要结局指标是6个月后证实的进展时间≥ 1.0 EDSS分（或0.5分，如果基线EDSS为5.5或更高）。次要结果包括EDSS的平均变化，多发性硬化症功能复合物的平均变化，MRI的变化，年复发率，和quality of life.Results：治疗组之间在主要或次要终点均无显著差异。MBP 8298在所有接受治疗的受试者中耐受良好，没有发现安全性问题。结论：在研究的人群中，与安慰剂相比，MBP 8298治疗没有提供临床益处。证据分类：本研究提供了1类证据，表明MBP 8298对HLA DR 2（+）或DR 4（+）的SPMS患者无效。神经病学（R）2011;77：1551-1560
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(+). Neurology (R) 2011;77:1551-1560