Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- The primary outcome measure is ocular and systemic safety of the treatment.
研究概览
简要总结
The purpose of this clinical trial is to examine the safety of gene therapy for Lebers Congenital Amaurosis (LCA) caused by RPE65 mutations using a recombinant adeno-associated virus serotype 2 (rAAV2) vector carrying the human RPE65 (hRPE65) gene. Recently, three independent short-term gene therapy studies in humans with LCA due to RPE65 mutations were published, suggesting that subretinal delivery of rAAV virus carrying the RPE65 gene is safe. As a secondary outcome, improvement in visual function was observed in seven of the first nine treated patients. The proposed study is a similar open label, Phase I clinical trial of uniocular subretinal rAAV2-hRPE65 administration to individuals with RPE65-associated retinal disease. Two cohorts of three subjects each and one cohort of four subjects will be included in this trial. Cohort 1 and 2 will consist of individuals 18 years of age and older and Cohorts 3 will consist of individuals 8 years of age and older. In cohort 2, a larger volume of vector will be administered. Enrollment in Cohort 3 will begin only after confirming the safety of rAAV2-hRPE65 administration in the older group of participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Retinal disease caused by homozygous or compound heterozygote RPE65 mutations;
- •Clinical diagnosis of Leber congenital amaurosis (LCA) with severely impaired visual and retinal function, and best corrected visual acuity of 20/50 or worse in the study eye;
- •Ability to perform tests of visual and retinal function;
- •Good general health;
- •Ability to comply with research procedures;
- •Specific for Cohort 1 and 2: 18 years of age and older;
- •Specific for Cohort 3: Over 8 years of age;
排除标准
- •Immune deficiency or use of immunosuppressive medications;
- •Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints (for example, glaucoma or ocular media opacities);
- •Complicating systemic diseases;
- •Impaired coagulation or use of anti-platelet agents within 7 days prior to study agent administration;
- •Pregnancy or breastfeeding;
- •Individuals (males and females) of childbearing potential who are unwilling to use effective contraception for 1 year following agent administration and barrier contraception for 3 months following agent administration;
- •Any other condition that would prevent a subject from completing follow-up examinations during the course of the study;
- •Any other condition that, in the opinion of the investigator, makes the subject unsuitable for the study;
- •Current or recent participation in any other research protocol involving investigational agents or therapies, including recent (within past 6 months) receipt of an investigational biologic therapeutic agent.
- •Subjects will not be excluded based on their gender, race or ethnicity.
研究组 & 干预措施
rAAV2-hRPE65
干预措施: rAAV2-hRPE65 (Genetic)
结局指标
主要结局
The primary outcome measure is ocular and systemic safety of the treatment.
时间窗: 3 years
次要结局
- Visual function, as quantified before and after vector administration.(3 years)