Safety and Efficacy of ZVS203e in the Treatment of Retinitis Pigmentosa Caused by RHO Gene Mutation

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.