ZVS101e in Patients With Bietti's Crystalline Dystrophy

Official title

Clinical Translation and Application Protocol for ZVS101e in the Gene Therapy of Bietti Crystalline Corneoretinal Dystrophy

Overview

The goal of this clinical trial is to evaluate the safety and early effectiveness of ZVS101e in patients with Bietti crystalline dystrophy who meet the eligibility criteria for treatment under the translational application program in the Hainan Boao Lecheng International Medical Tourism Pilot Zone. Participants will: undergo screening and baseline assessments to confirm eligibility; receive a single subretinal injection of ZVS101e in the study eye; complete follow-up visits over 4 weeks after treatment for safety monitoring and assessment of early effectiveness.

Interventions

• Drug ZVS101e
  ZVS101e injection contains a recombinant adeno-associated virus serotype 8 (rAAV8) vector that expresses human CYP4V2 protein.

Primary outcome measures

• Change from baseline in Best corrected visual acuity (BCVA) [Time frame: From enrollment to the end of treatment at 52 weeks]
• The incidence and severity of adverse events and serious adverse events [Time frame: From enrollment to the end of treatment at 52 weeks]

Eligibility criteria

Inclusion criteria

• Voluntarily participate in the research and sign the informed consent form, and be willing to complete the entire process according to the protocol requirements;
• Clinically diagnosed with Bietti's Crystalline Dystrophy (BCD), age ≥ 18 years;
• Confirmed by genetic testing to carry homozygous or compound heterozygous mutations in CYP4V2, and not complicated with other ophthalmic genetic diseases;
• Target eye BCVA ≤ 60 ETDRS letters.

Exclusion criteria

Subjects will be excluded if they meet any 1 of the following exclusion criteria:

• The target eye currently has or has a history of macular lesions; suffers from ocular diseases that may hinder surgery or interfere with the interpretation of study endpoints;
• The target eye has previously undergone retinal reattachment surgery, vitrectomy, or any intraocular surgery within 3 months before enrollment;
• Within 1 month before enrollment, suffered from viral infectious diseases that may affect the evaluation of the efficacy and safety of the investigational drug, or received antiviral vaccines;
• The target eye has previously received gene therapy or stem cell therapy for BCD or other ocular diseases;
• Known allergy to the drugs planned for use in the study;
• The laboratory abnormalities are considered clinically significant;
• Pregnant or lactating females.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• Boao Super Hospital — Qionghai
• Hainan Boao Ophthalmology Center, Zhongshan Ophthalmic Center, Sun Yat-sen University — Qionghai

Publications

• Wang J, Zhang J, Yu S, Li H, Chen S, Luo J, Wang H, Guan Y, Zhang H, Yin S, Wang H, Li H, Liu J, Zhu J, Yang Q, Sha Y, Zhang C, Yang Y, Yang X, Zhang X, Zhao X, Wang L, Yang L, Wei W. Gene replacement therapy in Bietti crystalline corneoretinal dystrophy: an open-label, single-arm, exploratory trial. Signal Transduct Target Ther. 2024 Apr 24;9(1):95. doi: 10.1038/s41392-024-01806-3. PMID 38653979
• Jia R, Meng X, Chen S, Zhang F, Du J, Liu X, Yang L. AAV-mediated gene-replacement therapy restores viability of BCD patient iPSC derived RPE cells and vision of Cyp4v3 knockout mice. Hum Mol Genet. 2023 Jan 1;32(1):122-138. doi: 10.1093/hmg/ddac181. PMID 35925866

Identifiers

NCT: NCT07653971 · ZYA-2025-003

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗