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.
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 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.
Single group
ZVS203e
DrugZVS203e injection is a clear, transparent liquid containing a recombinant adeno-associated virus serotype 8 (rAAV8) vector that expresses humanized SauriCas9 protein and single guide RNA (sgRNA) targeting specific mutations in the RHO gene.
Evaluate the safety and tolerability of subretinal injection of ZVS203e solution
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)
Change in best-corrected visual acuity (BCVA) of the treated eye at 24 weeks compared to baseline.
Change from Baseline in Visual function metrics
Treatment outcomes for visual function metrics include changes from baseline in LLVA, dynamic visual field, microperimetry, FST, contrast sensitivity, color vision, and mfERG; as well as changes from baseline in the NEI-VFQ-25 score reported by the participants.
Change from Baseline in OCT
Compare changes in retinal morphology and alterations in cell layers of the retina before and after drug administration.
Evaluate the immunogenicity of ZVS203e
Changes in SauriCas9 antibody, AAV8 antibody, and neutralizing antibody levels from baseline in the subjects.
Evaluate the pharmacokinetic characteristics of ZVS203e
Changes in AAV8 vector DNA and mRNA levels in the blood and tears of participants compared to baseline.
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