A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Efficacy of ManNAc in Subjects with GNE Myopathy

一项随机、双盲、安慰剂对照、多中心研究，旨在评估 ManNAc 对 GNE 肌病受试者的疗效

• 批准号: 10765494
• 负责人: ANTHONY Arnold AMATO
• 金额: $ 110.39万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10765494
• 关键词: Anabolism; Awareness; Caring; Development; Disease; Disease Progression; Double-Blind Method; Enzymes; Future; Knowledge; Modeling; Multicenter Studies; Multicenter Trials; Myopathy; Natural History; Orphan; Patient Recruitments; Patients; Placebo Control; Progressive Disease; Randomized; Safety; Sialic Acids; Wheelchairs; design; disability; double-blind placebo controlled trial; efficacy evaluation; first-in-human; mannosamine; novel; open label; patient population; phase I trial; phase II trial; recruit; tool; treatment effect

PROJECT SUMMARY GNE myopathy is a slowly progressive muscle disease resulting in marked disability, including wheelchair use, and ultimately requiring dependent care. Currently, there is no treatment available for GNE myopathy. N-acetyl-D-mannosamine monohydrate (ManNAc), the first committed precursor for the biosynthesis of Neu5Ac (sialic acid), and a substrate of the GNE enzyme defective in GNE myopathy, is being developed for this orphan indication. A first-in- human Phase 1 trial has been completed and an Open-Label Phase 2 trial is ongoing. We propose a randomized, double-blinded, placebo-controlled trial to evaluate the efficacy and safety of ManNAc in subjects with GNE myopathy. We hope that this study will inform future trials and will eventually lead to FDA approval for ManNAc in GNE myopathy. The primary efficacy endpoint and design of our proposed multicenter trial in 50 GNE myopathy subjects is based on knowledge collected for 5 years as part of an ongoing natural history study (NCT01417533; PI: Dr. Nuria Carrillo) which led to the development of the GNE Myopathy Disease Progression Model. This disease progression model is a novel tool that has allowed the design of a trial that overcomes the challenges of determining treatment effect in this rare and slowly progressive disease. The disease progression model facililates recruitment of subjects within a wide range of the disease spectrum, increasing the generalizability of our findings to the patient population. Furthermore, our strategy could be applied to other slowly progressive muscle diseases. Finally, we hope that our proposed trial and patient recruitment efforts will increase awareness of GNE myopathy and identification of undiagnosed patients. 1

项目总结

项目成果

Safety and efficacy of N-acetylmannosamine (ManNAc) in patients with GNE myopathy: an open-label phase 2 study.

• DOI: 10.1038/s41436-021-01259-x
• 发表时间: 2021-11
• 期刊: Genetics in medicine : official journal of the American College of Medical Genetics
• 作者: Carrillo N;Malicdan MC;Leoyklang P;Shrader JA;Joe G;Slota C;Perreault J;Heiss JD;Class B;Liu CY;Bradley K;Jodarski C;Ciccone C;Driscoll C;Parks R;Van Wart S;Bayman L;Coffey CS;Quintana M;Berry SM;Huizing M;Gahl WA
• 通讯作者: Gahl WA