An Investigator-initiated, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of HG005 in Pediatric Patients With Stargardt Disease (STGD1) Caused by Biallelic ABCA4 Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Incidence and severity of systemic adverse events
研究概览
简要总结
Stargardt disease type 1 (STGD1) is a rare genetic eye condition that causes progressive vision loss, often beginning in childhood or adolescence. It is the most common form of inherited macular degeneration and can lead to legal blindness. STGD1 is caused by mutations in the ABCA4 gene, which normally helps clear waste from the photoreceptor cells in the retina. When ABCA4 gene doesn't function properly, toxic substances like A2E accumulate and damage the retinal pigment epithelium (RPE), leading to vision loss.
There are currently no approved treatments for STGD1. HG005 is an investigational gene therapy designed to deliver a healthy copy of the ABCA4 gene to the retina. Because the gene is too large to fit into a single AAV (adeno-associated virus) vector, HG005 used two AAV vectors that work together in retinal cells to produce the full-length, functional ABCA4 protein. The goal of HG005 is to restore normal waste removal, protect retinal cells from further damage, and slow or stop vision loss.
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
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient ≥ 6 and ≤17 years at the time of signing informed consent, with clinical diagnosis of Stargardt disease;
- •At least one ABCA4 allele on each chromosome;
- •Both eyes must have well-defined macular atrophic lesions consistent with the diagnosis of Stargardt macular dystrophy.
- •Meet visual acuity criteria based on ETDRS letter chart
- •Subject must agree to contraception during the study.
- •Acceptable hematology, clinical chemistry, urine laboratory, and protocol required eye examination.
排除标准
- •Presence of active intraocular inflammation or uveitis history in either eye;
- •Presence of ocular or periocular infection history in either eye within 2 weeks prior to selection;
- •History or presence of corneal dystrophy in the study eye;
- •History of HIV or hepatitis A, B, or C infection;
- •Previous treatment with any gene therapy or cell therapy (e.g., stem cell transplantation);
- •Additional intraocular surgery in study eye 3 months prior to baseline visit;
- •Participation in an oral therapeutic STGD clinical trial within 3 months (or within 5 half-lives after last dose) prior to Screening
- •Any concomitant treatment that, in the opinion of the investigator, might interfere with the surgical procedure or healing process of the eye
- •Any other conditions that would not allow the potential subject to complete follow-up examinations during the study and would, in the opinion of the investigator, make the potential subject unsuitable for the study.
结局指标
主要结局
Incidence and severity of systemic adverse events
时间窗: 26 & 52 weeks
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
次要结局
- Change of study eye versus control eye in Low Luminance Visual Acuity(LLVA)(52 weeks)
- Change of study eye versus control eye in Fundus Autofluorescence (FAF)(52 weeks)
- Change of study eye versus control eye in Optical Coherence Tomography (OCT)(52 weeks)