Biostatistics Center for Lebers Hereditary Optic Neuropathy (LHON): Gene Therapy Clinical Trial

Leber遗传性视神经病变（LHON）的生物统计学中心（BC）：基因治疗 临床试验将继续与John Guy博士合作，逐步提高剂量。 AAV-ND 4基因治疗研究产品（IP）在这项1期临床试验中。LHON是一个 母系遗传性线粒体DNA致盲病（ND 4中的G11778 A突变） 基因）。Guy博士开发了一种异位表达的方法， 引入这种线粒体基因的“核版本”，然后在细胞质上靶向 将合成的蛋白质与线粒体靶向序列一起递送至线粒体。关于LHON 基因治疗临床试验是一项1期临床试验，旨在评估开放标签， 单侧、单剂量玻璃体内注射腺相关病毒载体（AAV-ND 4）LHON 患者BC为研究提供生物统计和协调中心支持。 BC研究人员是一个经验丰富的团队，他们参与了眼科 自1985年以来一直进行临床试验，并与Guy博士合作进行前瞻性资助的自然史研究。 一项LHON家族队列研究，其中包括受影响的患者和携带者。在 在这项I期剂量递增试验的上一个资助周期中，BC在以下方面发挥了关键作用： 启动试验并确保19名患者的合规入组和注射后随访， 其中18个证明了低和中剂量AAV-ND 4 IP的安全性。也是 负责数据质量、管理和录入21 CRF第11部分合规性 数据库这一努力导致了两份报告发表在同行评议眼科 文学 研究小组现在建议采用其程序，开发，实施，并证明 从低剂量和中剂量到更高剂量的递增

The Biostatistics Center (BC) for Leber's Hereditary Optic Neuropathy (LHON): Gene Therapy Clinical Trial will continue its collaboration with Dr. John Guy, escalating to higher doses of the AAV-ND4 gene therapy investigational product (IP) in this Phase 1 clinical trial. LHON is a maternally inherited blinding disease of mitochondrial DNA (G11778A mutation in the ND4 gene). Dr. Guy has developed a method for allotopic expression, which is a procedure to introduce a “nuclear version” of this mitochondrial gene and to then target the cytoplasmically synthesized protein to the mitochondria with a mitochondrial targeting sequence. The LHON Gene Therapy Clinical Trial is a Phase 1 clinical trial to evaluate the safety of an open-label, unilateral, single-dose of intravitreal injection of adenoassociated viral vector (AAV-ND4) LHON patients. The BC provides biostatistical and coordinating center support for the study. The BC investigators are an experienced team, who have been involved with ophthalmological clinical trials since 1985 and collaborated with Dr. Guy on a prospective funded natural history study of a cohort of LHON families, which included affected patients and carriers. In the previous funding cycle of this Phase I dose escalation trial, the BC played a critical role in initiating the trial and ensuring compliant enrollment and post injection follow up of 19 patients, 18 of which demonstrated safety of the low and medium dose AAV-ND4 IP. It is also responsible for data quality, management, and entry into the 21 CRF part 11 compliant database. This effort led to the publication of two reports in the peer-reviewed ophthalmology literature. The study team now proposes to employ its procedures, developed, implemented, and proven for the low and medium doses, to escalation of higher doses