A Phase 1/2 Safety Study in Subjects With CHM (Choroideremia) Gene Mutations Using an Adeno-Associated Virus Serotype 2 Vector to Deliver the Normal Human CHM Gene [AAV2-hCHM] to the Retina
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 6
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This clinical study evaluates the safety and tolerability of AAV2-hCHM in participants with Choroideremia gene mutations.
详细描述
The primary objective is to evaluate the safety and tolerability of subretinal administration of AAV2-hCHM, in an inter-subject group dose escalation in individuals with choroideremia, based on a comprehensive clinical monitoring plan. The secondary objectives are to define the dose of AAV2-hCHM required to achieve stable, or improved, visual function/functional vision and to assess development of immune responses to adeno-associated virus vector, serotype 2 (AAV2) and Rab escort protein 1 (REP-1).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male at least 18 years of age diagnosed with CHM gene mutation
- •Central visual field (VF) <30° in any of the 24 meridians (using Goldmann perimetry III4e isopter) in the eye to be injected
- •Any evidence of functioning outer retinal cells within the central 10°
排除标准
- •Previous history of ocular inflammatory disease (uveitis)
- •Prior intraocular surgery within six months
- •Participation in a previous gene therapy research trial within one year of enrollment or participation in any other ocular gene therapy trial
- •Participation in a clinical study with an investigational drug in the past six months
- •Grossly asymmetrical disease, or other eye morbidity, which may render the contralateral eye ineffective as a control
- •Visual acuity <20/200 on standard Early Treatment of Diabetic Retinopathy Study (ETDRS) testing in the eye to be injected
- •Presence of disease which may preclude the participant from participation in this trial
- •Use of medications known to be neuroprotective or retino-toxic that could potentially interfere with the disease process and/or cause ocular adverse events; individuals who discontinue use of these compounds for 6 months may become eligible
- •Identification by the investigator as being unable or unwilling to perform/be compliant with study procedures.
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to 5 years
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were AEs that occurred on or after the day of study drug administration. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
次要结局
- Number of Participants With Anti-AAV2 Viral Capsid Antibody Titers That Rose Above Baseline At Least Once After Dosing(Up to 2 years)
- Number of Participants With Cellular Immune Response to Rab Escore Protein-1 (REP-1) Through Interferon Gamma ELISPOT Assay(Up to 2 years)
- Number of Participants With Cellular Immune Response to AAV2 Through Interferon Gamma Enzyme-linked Immunosorbent Spot (ELISpot) Assay(Up to 2 years)