[Translation] A Phase 1/2/3, Multicenter, Phase 2 Clinical Study to Evaluate the Safety and Efficacy of Gene Therapy for ND4 Mutation-Associated Leber Hereditary Optic Neuropathy (LHON)
本临床研究的目的是选择最佳剂量,评价NR082治疗线粒体ND4基因突变导致LHON的安全性和有效性。第1阶段(1/2期)为安全性剂量探索研究,入组≥18岁且≤75岁的受试者单次单侧玻璃体内(IVT)注射NR082眼用注射液,并观察其安全性和有效性。第2阶段(3期)的临床研究使用第1阶段结束后的推荐剂量进一步验证研究药物的安全性和有效性。第2阶段研究分为安全导入期和随机、双盲、对照研究,入组年龄为≥12岁且≤75岁的受试者,导入期入组6例可评价受试者,监测至少6周后,如没有发现新的安全性信号,经过安全评估委员会(SRC)批准,可以进入随机、双盲、对照研究。所有受试者的临床表现为ND4突变的LHON引起的视力下降,中心实验室检测为G11778A位点突变(经CLIA认证的实验室),且视力下降持续时间>6个月且<10年。
[Translation] The purpose of this clinical study was to select the optimal dose and evaluate the safety and efficacy of NR082 in the treatment of LHON caused by mitochondrial ND4 gene mutation. Phase 1 (Phase 1/2) is a safety dose-finding study, enrolling subjects aged ≥18 and ≤75 years with a single unilateral intravitreal (IVT) injection of NR082 ophthalmic injection, and observing its safety and effectiveness. The Phase 2 (Phase 3) clinical study further validates the safety and efficacy of the investigational drug using the recommended dose after the end of Phase 1. The Phase 2 study is divided into a safety lead-in period and a randomized, double-blind, controlled study. Subjects aged ≥12 years and ≤75 years old are enrolled. During the lead-in period, 6 evaluable subjects are enrolled and monitored for at least 6 weeks. Afterwards, if no new safety signal is found, it can enter a randomized, double-blind, controlled study with the approval of the Safety Review Committee (SRC). All subjects had clinically manifested vision loss due to ND4-mutated LHON, central laboratory testing for G11778A site mutation (CLIA-certified laboratory), and vision loss lasting >6 months and <10 years.