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

NCT06952842 | Not Yet Recruiting Phase 1

• 1 other identifier: ZYB-2025-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Retinitis Pigmentosa

Keywords

Gene editing; ZVS203e; RHO; Retinitis pigmentosa

Outcome Measures

Primary Outcomes (2)

• 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.

  24 weeks post-treatment

• 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.

  24 weeks post-treatment

Secondary Outcomes (5)

• Change from Baseline in Visual function metrics

  24 weeks post-treatment

• Change from Baseline in OCT

  24 weeks post-treatment

• Evaluate the immunogenicity of ZVS203e

  24 weeks post-treatment

• Evaluate the pharmacokinetic characteristics of ZVS203e

  24 weeks post-treatment

• Change from Baseline in multi-luminance mobility test (MLMT)

  24 weeks post-treatment

Study Arms (1)

Single arm

EXPERIMENTAL

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

Drug: ZVS203e

Interventions

ZVS203e DRUG

ZVS203e 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.

Also known as: rAAV8

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chigenovo Co., Ltd: lead

Study Sites (1)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Related Publications (2)

• Liu X, Jia R, Meng X, Li Y, Yang L. Retinal degeneration in humanized mice expressing mutant rhodopsin under the control of the endogenous murine promoter. Exp Eye Res. 2022 Feb;215:108893. doi: 10.1016/j.exer.2021.108893. Epub 2021 Dec 14.

  PMID: 34919893 BACKGROUND

• Liu X, Qiao J, Jia R, Zhang F, Meng X, Li Y, Yang L. Allele-specific gene-editing approach for vision loss restoration in RHO-associated retinitis pigmentosa. Elife. 2023 Jun 5;12:e84065. doi: 10.7554/eLife.84065.

  PMID: 37272616 BACKGROUND

MeSH Terms

Conditions

Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Hongliang Dou, M.D.

  Peking University Third Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinlu Zhang, MD

CONTACT

15810570898; zhangjinlu@chinagene.cc

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: May 1, 2025
• Study Start: May 18, 2025
• Primary Completion (Estimated): June 18, 2030
• Study Completion (Estimated): June 18, 2045
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)