Safety and Tolerability of Carbamylated Erythropoietin in Friedreich's Ataxia
Safety and Tolerability of Carbamylated Erythropoietin in Friedreich's Ataxia
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DOI：
10.1002/mds.25836
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发表时间：
2014-06-01
影响因子：
8.6
通讯作者：
Manicom, Karen
中科院分区：
文献类型：
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作者：
Boesch, Sylvia;Nachbauer, Wolfgang;Manicom, Karen
背景：促红细胞生成素(EPO)衍生物在体外可增加Friedreich‘s共济失调(FRDA)患者的Frataxin水平。这项多中心、双盲、安慰剂对照的II期临床试验旨在评估Lu AA24493(氨基甲酰化EPO；CEPO)的安全性和耐受性。方法：36名携带>；400 GAA重复序列的门诊FRDA患者被随机分配到固定剂量的CEPO(每周3次，每次325微克)或安慰剂。安全性和耐受性在基线后103天进行评估。在基线后43天进行疗效的次要结果测量(探索生物标记物和共济失调分级)。结果：所有患者都接受了6剂研究药物。不良反应在CEPO和安慰剂之间平均分布。多次给药后未发现CEPO免疫原性的证据。生物标记物，如Frataxin，或氧化应激和共济失调评级的测量在CEPO和安慰剂之间没有差异。结论：CEPO在2周的治疗阶段是安全和耐受性良好的。次要结果指标在CEPO和安慰剂之间没有明显差异。(C)2014年国际帕金森病和运动障碍协会
Background: Erythropoietin (EPO) derivatives have been found to increase frataxin levels in Friedreich's ataxia (FRDA) in vitro. This multicenter, double-blind, placebo-controlled, phase II clinical trial aimed to evaluate the safety and tolerability of Lu AA24493 (carbamylated EPO; CEPO).Methods: Thirty-six ambulatory FRDA patients harboring >400 GAA repeats were 2:1 randomly assigned to either CEPO in a fixed dose (325 mu g thrice-weekly) or placebo. Safety and tolerability were assessed up to 103 days after baseline. Secondary outcome measures of efficacy (exploration of biomarkers and ataxia ratings) were performed up to 43 days after baseline.Results: All patients received six doses of study medication. Adverse events were equally distributed between CEPO and placebo. There was no evidence for immunogenicity of CEPO after multiple dosing. Biomarkers, such as frataxin, or measures for oxidative stress and ataxia ratings did not differ between CEPO and placebo.Conclusion: CEPO was safe and well tolerated in a 2week treatment phase. Secondary outcome measures remained without apparent difference between CEPO and placebo. (C) 2014 International Parkinson and Movement Disorder Society