Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study
Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study
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DOI：
10.1111/dme.12361
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发表时间：
2014-04-01
影响因子：
3.5
通讯作者：
Dayan, C. M.
中科院分区：
文献类型：
--
作者：
Ambery, P.;Donner, T. W.;Dayan, C. M.
目的研究Otelixizumab(3.1 mg，疗程8天)对初发1型糖尿病患者(12-17岁)的C-肽分泌是否有保护作用。方法将179例(54名青少年)患者随机分为两组。主要终点是12个月时曲线下2小时混合餐刺激的C肽区域的变化。由于Defare-1的疗效结果为阴性，2011年4月暂停了招生。结果治疗前后C肽变化无显著差异[增量=-0.09nmol/L(95%CI-0.17to 0；P=0.051)]。Otelixizumab在青少年中未见有不同的C-肽效应，且有更多不良事件的报道。结论Otelixizumab的有效性和耐受性与Defense-1相似。3.1毫克的剂量对成年人和青少年无效。需要进一步研究在较高剂量和治疗窗口下的作用机制。临床试验注册编号：NCT00763451
AimsPhaseIII DEFEND-2 investigated whether otelixizumab (3.1mg over 8days) preserved C-peptide secretion in patients with new-onset Type1 diabetes, focusing on adolescents (12-17years).MethodsOne hundred and seventy-nine patients (54 adolescents) were randomized to otelixizumab or placebo. The primary endpoint was change in 2-h mixed-meal-stimulated C-peptide area under the curve at month12. Enrolment was suspended in April 2011 following negative efficacy results from DEFEND-1. DEFEND-2 terminated early after 12months' efficacy and safety follow-up.ResultsChange from baseline C-peptide was not significantly different [ increment =-0.09nmol/l (95%CI -0.17 to 0; P=0.051)]. No differential C-peptide effect was seen for otelixizumab in adolescents and more adverse events were reported.ConclusionsEfficacy and tolerability of otelixizumab was similar to DEFEND-1. The 3.1-mg dose was non-efficacious in adults and adolescents. Further investigation of the mechanism of action seen at higher doses and therapeutic window is required.Clinical Trials Registry No: NCT00763451