Efficacy and Safety of ZVS101e in Patients With Bietti 's Crystalline Dystrophy

A Multicenter, Randomized，Controlled，Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of ZVS101e Administered as a Single Subretinal Injection in Subjects With Bietti's Crystalline Dystrophy (BCD)

This is a multi-center, randomized and controlled phase 3 clinical trial.

Study Overview

• Status: Recruiting
• Conditions: Bietti Crystalline Corneoretinal Dystrophy; Bietti Crystalline Dystrophy
• Intervention / Treatment: Drug: ZVS101e

Detailed Description

Subjects who have signed the written informed consent form and who were eligible for enrollment after screening will be randomly assigned to the treatment group or untreated control group. Each Participant in the treatment group will receive a unilateral subretinal injection of ZVS101e in the study eye.

Participants in the control group will receive no treatment during the first 52 weeks of enrollment.

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jinlu Zhang, MD; Phone Number: +86-15810570898; Email: zhangjinlu@chinagene.cc
• Study Contact Backup: Name: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Not yet recruiting
      • Peking University Third Hospital
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc
  • Guangdong
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • Zhongshan Ophthalmic Center, Sun Yat-sen University
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916
  • Heilongjiang
    • Haerbin, Heilongjiang, China
      • Not yet recruiting
      • The First Affiliated Hospital of Harbin Medical University
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc
  • Henan
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Provincial People's Hospital
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc
  • Shanghai
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • West China Hospital of Sichuan University
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Medical University Eye Hospital
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc
  • Zhejiang
    • Wenzhou, Zhejiang, China
      • Not yet recruiting
      • Eye Hospital, Wenzhou Medical University
      • Contact: Tingting Wu, BS; Phone Number: +86-18500191916; Email: wutingting@chinagene.cc

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. All of the following inclusion criteria should be met for enrollment into the trial:
2. Fully understand the purpose and requirements of this trial, voluntarily participate in the clinical trial and sign the informed consent form, and be able to complete all trial procedures as required by the protocol;
3. Clinical diagnosis of Bietti's crystalline dystrophy (BCD), age≥18 years ;
4. Genetic testing confirmed biallelic CYP4V2 mutations without other ophthalmic genetic diseases;
5. Best-corrected visual acuity of 5-60 ETDRS letters.

Exclusion Criteria:

1. The study eye has or has had macular lesions such as macular hole or macular neovascularization; glaucoma, diabetic retinopathy, or any other ocular disease that may preclude surgery or interfere with interpretation of the study endpoints
2. The study eye had received the following intraocular surgical treatments: retinal reattachment, vitrectomy;
3. The study eye had received any intraocular surgery, such as phacoemulsification 3 months prior to enrollment;
4. Previously treatment of either eye with gene therapy or stem cell therapy for BCD and other ocular diseases, including but not limited to viral vector gene therapy, RNA therapy;
5. Pregnant or lactating women;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; Each Participant in this group will receive a unilateral subretinal injection of ZVS101e in the study eye	Drug: ZVS101e; subretinal injection of ZVS101e; Other Names: AAV8-hCYP4V2; AAV2/8-hCYP4V2; Puliretgene parvec
No Intervention: Control group; Participants in the control group will receive no treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of study eyes with a ≥15-letter improvement from baseline in BCVA	Best corrected visual acuity (BCVA) will be assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. A 15-letter improvement over the baseline is clinical meaningful.	From baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in BCVA	Best corrected visual acuity (BCVA) will be assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The larger the letter number, the better the vision.	From baseline to Week 52
Proportion of study eyes with a ≥10-letter improvement from baseline in BCVA	Best corrected visual acuity (BCVA) will be assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.	From baseline to Week 52
Change from baseline in multi-luminance mobility test (MLMT) score	MLMT will be assessed using both eyes at different levels of illumination. A higher score indicates better functional vision.	From baseline to Week 52
Change from baseline in 25-Item visual function questionnaire (VFQ-25) score	National eye institute 25-item visual function questionnaire (NEI VFQ-25) consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively.	From baseline to Week 52
Change from Baseline in microperimetry	Microperimetry will be measured using MP-3，changes in retinal sensitivity (dB) will be analyzed.	From baseline to Week 52
Change from baseline in OCT	Retinal thickness will be assessed using OCT.	From baseline to Week 52
Incidence and severity of ocular and systemic adverse events	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.	From baseline to Week 52

Collaborators and Investigators

• Sponsor: Chigenovo Co., Ltd
• Investigators: Study Director: Jinlu Zhang, MD, 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 1, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: phase 3; gene replacement therapy; ZVS101e; AAV8-hCYP4V2; Bietti crystalline corneoretinal dystrophy
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Corneal Diseases; Eye Diseases, Hereditary; Retinal Diseases; Corneal Dystrophies, Hereditary
• Other Study ID Numbers: ZYA-2024-001

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
• product manufactured in and exported from the U.S.: No