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

Chigenovo

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Retinitis Pigmentosa

Treatments: Drug: ZVS203e

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT06952842

ZYB-2025-001

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with a clinical diagnosis of retinitis pigmentosa (RP) (aged 18 years or older);
2. RHO (c.403C>T, p.R135W) gene site-specific mutation was confirmed by genetic testing, and no other ophthalmic genetic diseases were complicated;
3. The researchers judged that the target eye had viable retinal photoreceptor cells and retinal pigment epithelial cells;
4. 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);
5. The subject and his or her spouse agree to use effective contraception during the trial period and for at least 1 year after dosing;
6. Voluntarily participate in clinical trials and sign informed consent, and can complete the whole test process according to the protocol requirements.

Exclusion criteria

1. The researcher determined that the target eye currently has or had macular lesions such as macular hiatal hole or macular neovascularization;
2. 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.
3. Within 3 months prior to enrollment, the study eye had received any intraocular surgery, such as phacoemulsification cataract extraction.
4. The study eye had undergone retinal reattachment or vitrectomy.
5. Participants who had participated in any drug or medical device clinical trial within 3 months before enrollment;
6. 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.
7. 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).
8. Known allergy to the drug planned to be used in the study.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Single arm

Experimental group

Description:

All patients enrolled in the study will receive a single subretinal injection of ZVS203e in one eye

Treatment:

Drug: ZVS203e