A Single-Arm, Open-Label, Phase 1/2 Clinical Trial of ZVS203e in Subjects With Retinitis Pigmentosa Associated With RHO Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Evaluate the safety and tolerability of subretinal injection of ZVS203e solution
研究概览
简要总结
This trial employs a single-arm, open-label seamless Phase I/II design, consisting of two stages: Phase I dose exploration and Phase II dose expansion.The primary objective of this trial is to evaluate the safety, tolerability, and efficacy of subretinal injection of ZVS203e solution.
详细描述
ZVS203e injection is administered via a single subretinal injection of rAAV8 vector carrying CRISPR/Cas9 gene-editing tools to silence mutated genes, allowing retinal cells to express only normal functional proteins, thereby treating RHO-adRP.
This trial employs a single-arm, open-label seamless Phase I/II design, consisting of two stages: Phase I dose escalation and Phase II dose expansion, with an anticipated total enrollment of 9 to 18 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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a clinical diagnosis of retinitis pigmentosa (RP) (aged 18 years or older);
- •RHO (c.403C>T, p.R135W) gene site-specific mutation was confirmed by genetic testing, and no other ophthalmic genetic diseases were complicated;
- •The researchers judged that the target eye had viable retinal photoreceptor cells and retinal pigment epithelial cells;
- •The best corrected visual acuity of the target eye is between 2.0 LogMAR and 0.5 LogMAR (including 2.0 LogMAR and 0.5 LogMAR, which is equivalent to a number of fingers to 60 letters);
- •The subject and his or her spouse agree to use effective contraception during the trial period and for at least 1 year after dosing;
- •Voluntarily participate in clinical trials and sign informed consent, and can complete the whole test process according to the protocol requirements.
排除标准
- •The researcher determined that the target eye currently has or had macular lesions such as macular hiatal hole or macular neovascularization;
- •Have other eye conditions that may prevent surgery or interfere with interpretation of the study endpoint, such as glaucoma, diabetic retinopathy, eye or periocular infections, active endophthalmitis, etc.
- •Within 3 months prior to enrollment, the study eye had received any intraocular surgery, such as phacoemulsification cataract extraction.
- •The study eye had undergone retinal reattachment or vitrectomy.
- •Participants who had participated in any drug or medical device clinical trial within 3 months before enrollment;
- •Previously treatment of either eye with gene therapy or stem cell therapy for RP and other ocular diseases, including but not limited to viral vector gene therapy, RNA therapy.
- •Treatment with medications that may affect the efficacy and safety evaluation of the investigational product within 3 months prior to enrollment (e.g., ranibizumab, bevacizumab, aflibercept, conbercept).
- •Known allergy to the drug planned to be used in the study.
研究组 & 干预措施
Single arm
All patients enrolled in the study will receive a single subretinal injection of ZVS203e in one eye
干预措施: ZVS203e (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of subretinal injection of ZVS203e solution
时间窗: 24 weeks post-treatment
Types, severity, and incidence of adverse events (AE) and serious adverse events (SAE) in the eyes and throughout the body within 24 weeks post-treatment, including dose-limiting toxicities (DLT) during the dose escalation phase.
Change from baseline in best-corrected visual acuity (BCVA)
时间窗: 24 weeks post-treatment
Change in best-corrected visual acuity (BCVA) of the treated eye at 24 weeks compared to baseline.
次要结局
- Change from Baseline in OCT(24 weeks post-treatment)
- Evaluate the pharmacokinetic characteristics of ZVS203e(24 weeks post-treatment)
- Change from Baseline in Visual function metrics(24 weeks post-treatment)
- Evaluate the immunogenicity of ZVS203e(24 weeks post-treatment)
- Change from Baseline in multi-luminance mobility test (MLMT)(24 weeks post-treatment)