A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing CNGB3 in Patients With Congenital Achromatopsia Caused by Mutations in the CNGB3 Gene
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 32
- 试验地点
- 16
- 主要终点
- Adverse events
研究概览
简要总结
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.
详细描述
This will be a non-randomized, open-label, Phase 1/2 study of the safety and efficacy of AGTC-401 administered to one eye by subretinal injection in individuals with achromatopsia caused by mutations in the CNGB3 gene. The primary study endpoint will be safety and the secondary study endpoint will be efficacy.
Subjects will be enrolled sequentially in seven dosing groups. Subjects in Groups 1, 2, 3, 4, 5, and 6 will be at least 18 years of age and will receive varying dose levels of study agent. Subjects in Group 4a will be 6 to 17 years of age and will receive the same dose as Group 4. Subjects in Groups 5a and 7 will be between 4 and 8 years of age. Subjects in Group 5a will receive the same dose as Group 5, and subjects in Group 7 will receive the maximum tolerated dose identified in Groups 1, 2, 3, 4, 4a, 5, 5a, and 6.
Safety will be monitored by evaluation of ocular and non-ocular adverse events and hematology and clinical chemistry parameters. Efficacy parameters will include visual acuity, light discomfort testing, color vision, static visual field, ERG, adaptive optics retinal imaging, functional MRI (fMRI), color brightness test and OCT.
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
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects with documented mutations in both alleles of the CNGB3 gene;
- •Retinal disease consistent with a clinical diagnosis of achromatopsia;
- •At least 18 years of age for Groups 1, 2, 3, 4, 5 and
- •At least 6 years of age for Group 4a, and 4-8 years of age for Groups 5a and 7;
- •Able to perform tests of visual and retinal function;
- •Visual acuity in the study eye not better than 55 ETDRS letters (Snellen equivalent 20/80) based on the average of two examinations at the baseline visit;
- •Acceptable laboratory parameters;
- •For females of childbearing potential: A negative pregnancy test within 2 days before administration of study agent.
排除标准
- •Best-corrected visual acuity difference between the two eyes of > 15 ETDRS letters (3 lines);
- •Evidence of degenerative myopia in the study eye;
- •Pre-existing eye conditions that would contribute to vision loss in either eye or increase the risk of subretinal injection in the study eye.
结局指标
主要结局
Adverse events
时间窗: 1 year
Proportion of participants experiencing grade 3 or greater adverse events
次要结局
- Visual acuity(1 year)
- Light aversion(1 year)
- Color vision(1 year)