Compassionate Administration of ZVS101e for Extended Treatment

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).

Study Overview

• Status: Enrolling by invitation
• Conditions: Bietti Crystalline Corneoretinal Dystrophy
• Intervention / Treatment: Drug: ZVS101e

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 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.
2. Voluntarily participate in clinical trials and sign informed consent forms, and be willing to complete all trial procedures as required by the protocol.
3. Study the BCVA of the eye ≤60 ETDRS letters.

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. 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.
5. Known to be allergic to the drugs planned to be used in the study.

6. 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).

7. Pregnant or lactating women.

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: ZVS101e treatment; The study eye of the subject receives a subretinal injection of ZVS101e.	Drug: ZVS101e; ZVS101e is a recombinant adeno-associated virus serotype 8 (rAAV8) vector expressing human CYP4V2 protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events and serious adverse events	This study specifies that the recording of adverse events begins on Day 0 (D0). Adverse events (AEs) include, but are not limited to, the following: Worsening of pre-existing medical conditions/diseases (i.e., conditions present prior to enrollment in the clinical trial), including exacerbation of symptoms, signs, frequency of episodes, or abnormal laboratory test results;; Any newly occurring adverse medical conditions (including symptoms, signs, or newly diagnosed diseases);; Abnormal laboratory test values or results with clinical significance, or other safety assessments (e.g., vital signs measurements).	4 weeks

Collaborators and Investigators

• Sponsor: Chigenovo Co., Ltd

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: December 14, 2025
• First Submitted That Met QC Criteria: December 14, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bietti Crystalline Dystrophy
• Other Study ID Numbers: ZYA-2025-004

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