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

A Single-Arm, Open-Label, Phase 1/2 Clinical Trial of ZVS203e in Subjects With Retinitis Pigmentosa Associated With RHO Mutation

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Drug: ZVS203e

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jinlu Zhang, MD; Phone Number: 15810570898; Email: zhangjinlu@chinagene.cc

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single arm; All patients enrolled in the study will receive a single subretinal injection of ZVS203e in one eye	Drug: ZVS203e; 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.; Other Names: rAAV8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 weeks post-treatment
Change from Baseline in OCT	Compare changes in retinal morphology and alterations in cell layers of the retina before and after drug administration.	24 weeks post-treatment
Evaluate the immunogenicity of ZVS203e	Changes in SauriCas9 antibody, AAV8 antibody, and neutralizing antibody levels from baseline in the subjects.	24 weeks post-treatment
Evaluate the pharmacokinetic characteristics of ZVS203e	Changes in AAV8 vector DNA and mRNA levels in the blood and tears of participants compared to baseline.	24 weeks post-treatment
Change from Baseline in multi-luminance mobility test (MLMT)	MLMT was assessed using both eyes at 1 or more of 7 levels of illumination, ranging from 400 lux (a brightly lit office) to 1 lux (a moonless summer night).	24 weeks post-treatment

Collaborators and Investigators

• Sponsor: Chigenovo Co., Ltd
• Investigators: Principal Investigator: Hongliang Dou, M.D., Peking University Third Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 18, 2025
• Primary Completion (Estimated): June 18, 2030
• Study Completion (Estimated): June 18, 2045

Study Registration Dates

• First Submitted: April 22, 2025
• First Submitted That Met QC Criteria: April 28, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): May 1, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Retinitis pigmentosa; RHO; Gene editing; ZVS203e
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: ZYB-2025-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No