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

NCT ID: NCT06952842

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-18
• Study Completion Date: 2045-06-18

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.

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.

Conditions

Retinitis Pigmentosa

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm

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

Group Type: EXPERIMENTAL

ZVS203e

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

rAAV8

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chigenovo Co., Ltd

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hongliang Dou, M.D.

Role: PRINCIPAL_INVESTIGATOR

Peking University Third Hospital

Locations

Peking University Third Hospital

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Jinlu Zhang, MD

Role: CONTACT

zhangjinlu@chinagene.cc

15810570898

References

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.

Reference Type: BACKGROUND

PMID: 34919893 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37272616 (View on PubMed)

Other Identifiers

ZYB-2025-001

Identifier Type: -

Identifier Source: org_study_id