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黏多糖贮积症VI型的酶替代疗法：一项3期、随机、双盲、安慰剂对照、多国重组人N-乙酰半乳糖胺4-硫酸酯酶（重组人芳基硫酸酯酶B或rhASB）研究及后续开放标签扩展研究。

Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study.

作者信息

Harmatz Paul, Giugliani Roberto, Schwartz Ida, Guffon Nathalie, Teles Elisa Leão, Miranda M Clara Sá, Wraith J Edmond, Beck Michael, Arash Laila, Scarpa Maurizio, Yu Zi-Fan, Wittes Janet, Berger Kenneth I, Newman Mary S, Lowe Ann M, Kakkis Emil, Swiedler Stuart J

机构信息

Children's Hospital & Research Center at Oakland, California 94609, USA, and Children's Hospital, University of Mainz, Germany.

出版信息

J Pediatr. 2006 Apr;148(4):533-539. doi: 10.1016/j.jpeds.2005.12.014.

DOI:10.1016/j.jpeds.2005.12.014

PMID:16647419

Abstract

OBJECTIVE

The objective of this Phase 3 study was to confirm the efficacy and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome), a rare, fatal lysosomal storage disease with no effective treatment.

STUDY DESIGN

Thirty-nine patients with MPS VI were evaluated in a randomized, double-blind, placebo-controlled, multicenter, multinational study for 24 weeks. The primary efficacy variable was the distance walked in a 12-minute walk test (12MWT), whereas the secondary efficacy variables were the number of stairs climbed in a 3-minute stair climb (3MSC) and the level of urinary glycosaminoglycan (GAG) excretion. All patients received drug in an open-label extension period for an additional 24 weeks.

RESULTS

After 24 weeks, patients receiving rhASB walked on average 92 meters (m) more in the 12MWT (p=.025) and 5.7 stairs per minute more 3MSC (p=.053) than patients receiving placebo. Continued improvement was observed during the extension study. Urinary GAG declined by -227+/-18 microg/mg more with rhASB than placebo (p<.001). Infusions were generally safe and well tolerated. Patients exposed to drug experienced positive clinical benefit despite the presence of antibody to the protein.

CONCLUSION

rhASB significantly improves endurance, reduces GAG, and has an acceptable safety profile.

摘要

目的

本3期研究的目的是确认重组人芳基硫酸酯酶B（rhASB）治疗黏多糖贮积症VI型（MPS VI；马罗-拉米综合征）的疗效和安全性，MPS VI是一种罕见的致命性溶酶体贮积病，尚无有效治疗方法。

研究设计

39例MPS VI患者参与了一项随机、双盲、安慰剂对照、多中心、跨国研究，为期24周。主要疗效变量是12分钟步行试验（12MWT）中的步行距离，次要疗效变量是3分钟爬楼梯试验（3MSC）中的爬楼梯数量和尿糖胺聚糖（GAG）排泄水平。所有患者在开放标签延长期接受药物治疗，为期24周。

结果

24周后，接受rhASB治疗的患者在12MWT中的平均步行距离比接受安慰剂的患者多92米（p = 0.025），在3MSC中每分钟多爬5.7级楼梯（p = 0.053）。在延长期研究中观察到持续改善。与安慰剂相比，rhASB治疗使尿GAG下降幅度多-227±18微克/毫克（p<0.001）。输液总体安全且耐受性良好。尽管存在针对该蛋白的抗体，但接受药物治疗的患者仍获得了积极的临床益处。