A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome)
A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome)
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DOI：
10.1016/j.ymgme.2006.09.001
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发表时间：
2007-03-01
影响因子：
3.8
通讯作者：
Kimura, Alan
中科院分区：
文献类型：
--
作者：
Muenzer, Joseph;Gucsavas-Calikoglu, Muge;Kimura, Alan
目的：评价艾杜磺酶(重组人艾杜糖酸盐-2-硫酸酯酶)治疗粘多糖病11例(NIPS 11)的安全性和有效性。研究设计：12例患者进入随机、双盲、安慰剂对照试验，为期24周，随后进行开放标签扩展研究。3组4名患者依次入选，每组3名患者服用艾度硫酶，1名患者服用安慰剂。第一组每隔一周静脉滴注艾度硫酶0.15 mg/kg，第二组和第三组分别给予0.5和1.5 mg/kg。24周后，接受安慰剂治疗的患者按照他们所在组的剂量改用艾度硫酶。主要终点是尿中糖胺聚糖排泄量与基线相比的变化。结果：尿糖胺多聚糖在2周内减少，48周后减少49%(P<；0.0001)。肝脾体积在24周(P<；0.01)和48周(P<；0.001)均有缩小。6分钟步行距离48周后平均增加48米(P=0.013)。在高剂量组中有6名患者出现了不影响艾度磺胺临床疗效的免疫球蛋白抗体。结论：这项研究描述了首次使用酶替代疗法治疗MPS II患者的经验。艾度硫酶总体耐受性良好，与尿糖胺聚糖水平和器官大小的减少以及6分钟步行试验距离的增加有关。(C)2006 Elsevier Inc.保留所有权利。
Objective: To evaluate the safety and explore the efficacy of idursulfase (recombinant human iduronate-2-sulfatase) treatment for mucopolysaccharidosis 11 (NIPS 11).Study design: Twelve patients were enrolled into a randomized, double-blind, placebo-controlled trial for 24 weeks followed by an open-label extension study. Three groups of 4 patients were enrolled sequentially, with 3 patients in each group receiving idursulfase and I patient receiving placebo. The first group received idursulfase at 0.15 mg/kg infused every other week with the 2nd and 3rd groups receiving 0.5 and 1.5 mg/kg, respectively. After 24 weeks the placebo-treated patients were changed to idursulfase at the dose of their group. The primary endpoint was a change from baseline in urinary excretion of glycosaminoglycans. Results were pooled for analysis by ANOVA and compared to baseline.Results: Urinary glycosaminoglycans were reduced within 2 weeks of initiating idursulfase and were decreased 49% after 48 weeks of treatment (P < 0.0001). Both liver and spleen volume were decreased at 24 weeks (P < 0.01) and 48 weeks (P < 0.001). The 6-minute walk test distance increased an average of 48 meters after 48 weeks (P = 0.013). Six patients in the higher dose groups developed IgG antibodies that did not influence the clinical effects of idursulfase.Conclusions: This study describes the first experience with enzyme replacement therapy for the treatment of patients with MPS II. Idursulfase was generally well tolerated and was associated with reductions in urine glycosaminoglycans levels and organ size, as well as an increased 6-minute walk test distance. (c) 2006 Elsevier Inc. All rights reserved.