A Phase 1, Open-label, Multiple-cohort, Dose-escalation Study to Evaluate the Safety and Tolerability of HG202 High-fidelity CRISPR-Cas13 (hfCas13Y) RNA-targeting Therapy for Neovascular Age-related Macular Degeneration (nAMD)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15
- 主要终点
- Incidence and severity of ocular and systemic adverse events
研究概览
简要总结
Age-related macular degeneration (AMD) leads to severe and irreversible vision loss, while neovascular AMD (nAMD) accounts for 80-90% of AMD blindness. Current anti-VEGF therapies are the standard of care, but these therapies require life-long repeated intraocular injections. These frequent intravitreal injections increase the risk of complications, including submacular hemorrhage, intraocular hypertension, inflammation, and retinal detachment. Therefore, repeated treatments for nAMD place a substantial burden on healthcare systems, patients, and their caregivers. Additionally, approximately 25-35% of individuals with aggressive nAMD show suboptimal responses to the anti-VEGF therapies, experience treatment-extended failure, or require intensive, frequent intraocular injections, and do not prevent irreversible vision loss.
HG202 is a CRISPR/Cas13 RNA-editing therapy delivered through one single AAV vector to partially knock down the expression of VEGFA and thus inhibit CNV formation in AMD. The long-term, stable delivery of HG202 following a one-time gene-editing therapy treatment for nAMD may potentially reduce the frequent injections and the potential risks of currently available anti-VEGF therapies since it does not rely on the long-term expression of anti-VEGF antibodies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females ≥ 50 and ≤ 85 years at the time of signing the ICF;
- •Active macular choroidal neovascularization (MNV) secondary to nAMD in the study eye;
- •Sentinel (1st) subject for each dose cohort must have a BCVA ≤ 20/63 and ≥ 20/400 (≤63 and ≥ 19 ETDRS letters) in the study eye. Following the sentinel subject evaluation, the rest of the subjects in the dose cohort must have a BCVA between ≤ 20/40 and ≥ 20/400 (≤ 73 and ≥ 19 ETDRS letters) in the study eye.
- •Able to perform visual acuity and retinal function tests and able and willing to comply with study procedures for this clinical trial.
排除标准
- •Retinal or subretinal hemorrhage, scarring, or fibrosis of greater than 50% of the total lesion in the study eye;
- •Other ocular diseases that may affect central vision in the study eye;
- •Any other cause of CNV than nAMD in the study eye
- •Uncontrolled glaucoma in the study eye;
- •History or presence of corneal transplant or corneal dystrophy in the study eye;
- •History of other intraocular surgery in the study eye within 3 months prior to baseline;
- •Prior gene therapy or oligonucleotide therapy;
- •Other conditions judged by the investigator as inappropriate for the study.
结局指标
主要结局
Incidence and severity of ocular and systemic adverse events
时间窗: 52 weeks
Number of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
次要结局
- Mean change from baseline in best-corrected visual acuity (BCVA)(52 weeks)
- Mean change in annualized rate of supplemental injections(52 weeks)