Compassionate Administration of ZVS101e for Extended Treatment

Overview

To provide treatment options for the control group of subjects who completed the 52-week follow-up of the Phase III clinical trial (Protocol number: ZYA-2024-001) of ZVS101e in subjects with Bietti crystalline corneoretinal dystrophy (BCD).

Detailed description

The trial period lasts for a total of 8 weeks, including a 4-week screening period, a administration period, and visits on the 1st day, 7th day, and 4th week after administration. The patients will be followed up at the research center on the 1st day, 7th day and 4th week after administration to evaluate the safety.

Interventions

• Drug ZVS101e
  ZVS101e is a recombinant adeno-associated virus serotype 8 (rAAV8) vector expressing human CYP4V2 protein

Primary outcome measures

• Incidence and severity of adverse events and serious adverse events [Time frame: 4 weeks]

Eligibility criteria

Inclusion criteria

• Subjects who were randomly assigned as the control group in a multicenter, randomized controlled, Phase III clinical trial (Protocol number: ZYA-2024-001) on the efficacy and safety of a single subretinal injection of ZVS101e in subjects with BCD and completed a 52-week safety follow-up were included.
• Voluntarily participate in clinical trials and sign informed consent forms, and be willing to complete all trial procedures as required by the protocol.
• Study the BCVA of the eye ≤60 ETDRS letters.

Exclusion criteria

• The study eye currently has or has had macular degeneration such as macular holes or neovascularization in the macular area; Other ocular diseases such as glaucoma and diabetic retinopathy that may hinder surgery or interfere with the interpretation of the study endpoint.
• The study eye had undergone retinal repositioning surgery, vitrectomy, or had undergone any intraocular surgery within 3 months prior to enrollment, such as phacoemulsification for cataract.
• Within one month prior to enrollment, the patient had a viral infectious disease that may affect the efficacy and safety evaluation of the investigational drug or had received an antiviral vaccine.
• Any eye has previously received gene therapy or stem cell therapy for BCD and other ocular diseases, including but not limited to other viral vector gene therapies, mRNA therapies, etc.
• Known to be allergic to the drugs planned to be used in the study.
• The following laboratory test abnormalities have clinical significance:

Liver function: ALT or AST>2 times the upper limit of the normal value; Abnormal coagulation function (prothrombin time ≥ the upper limit of normal value by 3 seconds, activated partial thromboplastin time ≥ the upper limit of normal value by 10 seconds).

• Pregnant or lactating women.

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 · 5 centers

• Peking University Third Hospital — Beijing
• Zhongshan Ophthalmic Center, Sun Yat-sen University — Guangzhou
• Henan Provincial People's Hospital — Zhengzhou
• West China Hospital, Sichuan University — Chengdu
• Tianjin Medical University Eye Hospital — Tianjin

Publications

• Yang L, Li W, Zhang J, Chen S, Qiao J, Qu B, Zhang F, Shen X, Leung HYE, Lam DSC. ZVS101e: AAV-mediated gene replacement therapy for Bietti crystalline corneoretinal dystrophy (BCD). Asia Pac J Ophthalmol (Phila). 2026 May-Jun;15(3):100320. doi: 10.1016/j.apjo.2026.100320. Epub 2026 Apr 21. PMID 42025802
• Jia R, Chen S, Li W, Zhang J, Qu B, Qiao J, Meng X, Yu S, Liu X, Xu B, Chen T, Shen X, Sun W, Dou H, Mahajan VB, Zhang Q, Yang L. Unravelling CYP4V2: Clinical features, genetic insights, pathogenic mechanisms and therapeutic strategies in Bietti crystalline corneoretinal dystrophy. Prog Retin Eye Res. 2025 Jul;107:101377. doi: 10.1016/j.preteyeres.2025.101377. Epub 2025 Jun 5. PMID 40482806
• 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
• 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
• Yang L, Xing D, Zhang J, Liu B, Jiang X, Chen S, Li W, Qu B, Qiao J, Feng X, Jia H, Hu X, Yu S, Jia R, Wang L, Mahajan VB, Dou H, Lu F, Li X. Gene therapy for Bietti crystalline corneoretinal dystrophy: A phase 1/2 clinical trial. Mol Ther. 2026 Mar 4;34(3):1743-1755. doi: 10.1016/j.ymthe.2026.01.005. Epub 2026 Jan 10. PMID 41520174

Identifiers

NCT: NCT07307469 · ZYA-2025-004

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗