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This is a multi-center, randomized and controlled phase 3 clinical trial.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment group | Experimental | Each Participant in this group will receive a unilateral subretinal injection of ZVS101e in the study eye |
|
| Control group | No Intervention | Participants in the control group will receive no treatment |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ZVS101e | Drug | subretinal injection of ZVS101e |
|
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jinlu Zhang, MD | Chigenovo Co., Ltd | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Beijing | Beijing Municipality | China | |||
| Zhongshan Ophthalmic Center, Sun Yat-sen University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40482806 | Background | 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. | |
| 41520174 |
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| ID | Term |
|---|---|
| C535440 | Bietti Crystalline Dystrophy |
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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 |
| Guangzhou |
| Guangdong |
| China |
| The First Affiliated Hospital of Harbin Medical University | Haerbin | Heilongjiang | China |
| Henan Provincial People's Hospital | Zhengzhou | Henan | China |
| Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine | Shanghai | Shanghai Municipality | China |
| West China Hospital of Sichuan University | Chengdu | Sichuan | China |
| Tianjin Medical University Eye Hospital | Tianjin | Tianjin Municipality | China |
| Eye Hospital, Wenzhou Medical University | Wenzhou | Zhejiang | China |
| Background |
| 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. |
| 42025802 | Background | 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. |
| 35925866 | Background | 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. |
| 38653979 | Background | 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. |