Bietti Crystalline Corneoretinal DystrophyPhase 3NCT06743646
Efficacy and Safety of ZVS101e in Patients With Bietti 's Crystalline Dystrophy
A Phase 3 study testing ZVS101e in people with Bietti Crystalline Corneoretinal Dystrophy and Bietti Crystalline Dystrophy, run by Chigenovo Co., Ltd at 5 sites in China.
Trial summary
This is a multi-center, randomized and controlled phase 3 clinical trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bietti Crystalline Corneoretinal Dystrophy, Bietti Crystalline Dystrophy
- What is being tested?
- ZVS101e
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 5 sitesChina
- Study dates
- 27 Dec 2024to 30 Jun 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All of the following inclusion criteria should be met for enrollment into the trial:
- 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;
- Clinical diagnosis of Bietti's crystalline dystrophy (BCD), age≥18 years ;
- Genetic testing confirmed biallelic CYP4V2 mutations without other ophthalmic genetic diseases;
- Best-corrected visual acuity of 5-60 ETDRS letters.
Who cannot join
- 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
- The study eye had received the following intraocular surgical treatments: retinal reattachment, vitrectomy;
- The study eye had received any intraocular surgery, such as phacoemulsification 3 months prior to enrollment;
- 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;
- Pregnant or lactating women;
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Peking University Third Hospital
Beijing, Beijing Municipality
West China Hospital of Sichuan University
Chengdu, Sichuan
Zhongshan Ophthalmic Center, Sun Yat-sen University
Guangzhou, Guangdong
Tianjin Medical University Eye Hospital
Tianjin, Tianjin Municipality
Henan Provincial People's Hospital
Zhengzhou, Henan
About this study
Official title: 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.
Read the 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.
- Being tested
- ZVS101e
- Keywords
- gene replacement therapy, ZVS101e, AAV8-hCYP4V2, phase 3, Bietti crystalline corneoretinal dystrophy
- Medical subject headings
- Bietti Crystalline Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZVS101eDrug
Also called AAV8-hCYP4V2, AAV2/8-hCYP4V2, Puliretgene parvec
subretinal injection of ZVS101e
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | Each Participant in this group will receive a unilateral subretinal injection of ZVS101e in the study eye Receives: Drug: ZVS101e |
| Control group | No intervention | Participants in the control group will receive no treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to Week 52
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From baseline to Week 52
Change from baseline in OCT
Retinal thickness will be assessed using OCT.
Measured: 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.
Measured: From baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2024
- Study start27 Dec 2024
- Primary completion20 Apr 2026
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Bietti Crystalline Corneoretinal DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chigenovo Co., Ltd
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Jinlu Zhang, MD, Study director, Chigenovo Co., Ltd
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06743646
- Sponsor's protocol ID
- ZYA-2024-001
- Status last verified
- Oct 2026
- First submitted
- 17 Dec 2024
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40482806Yang 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.
PubMed 41520174Yang 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.
PubMed 42025802Jia 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.
PubMed 35925866Wang 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.
PubMed 38653979
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT06743646
- Acronym / sponsor ID
- ZYA-2024-001
- Keywords
- gene replacement therapy, ZVS101e, AAV8-hCYP4V2, phase 3, Bietti crystalline corneoretinal dystrophy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 63 participants (actual)
- Lead sponsor
- Chigenovo Co., LtdResearch network
- Study start
- 27 Dec 2024 (actual)
- Primary completion
- 20 Apr 2026 (actual)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 20 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, randomized and controlled phase 3 clinical trial.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: ZVS101eEach 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- All of the following inclusion criteria should be met for enrollment into the trial:
- 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;
- Clinical diagnosis of Bietti's crystalline dystrophy (BCD), age≥18 years ;
- Genetic testing confirmed biallelic CYP4V2 mutations without other ophthalmic genetic diseases;
- Best-corrected visual acuity of 5-60 ETDRS letters.
Key exclusion criteria (5 listed)
- 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
- The study eye had received the following intraocular surgical treatments: retinal reattachment, vitrectomy;
- The study eye had received any intraocular surgery, such as phacoemulsification 3 months prior to enrollment;
- 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;
- Pregnant or lactating women;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZVS101eAlso: AAV8-hCYP4V2, AAV2/8-hCYP4V2, Puliretgene parvecsubretinal injection of ZVS101e | Drug | Treatment group |
Primary outcome
Proportion of study eyes with a ≥15-letter improvement from baseline in BCVA
Time frame: From baseline to Week 52
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.
7 secondary outcomes
Change from Baseline in BCVA
Time frame: From baseline to Week 52
Proportion of study eyes with a ≥10-letter improvement from baseline in BCVA
Time frame: From baseline to Week 52
Change from baseline in multi-luminance mobility test (MLMT) score
Time frame: From baseline to Week 52
Change from baseline in 25-Item visual function questionnaire (VFQ-25) score
Time frame: From baseline to Week 52
Change from Baseline in microperimetry
Time frame: From baseline to Week 52
Change from baseline in OCT
Time frame: From baseline to Week 52
Incidence and severity of ocular and systemic adverse events
Time frame: From baseline to Week 52
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Background: PubMed 40482806Jia 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.
- Background: PubMed 41520174Yang 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.
- Background: PubMed 42025802Yang 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.
- Background: PubMed 35925866Jia 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.
- Background: PubMed 38653979Wang 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jinlu Zhang, MD study director
Chigenovo Co., Ltd
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ZVS101e in people with Bietti Crystalline Corneoretinal Dystrophy and Bietti Crystalline Dystrophy, run by Chigenovo Co., Ltd at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of study eyes with a ≥15-letter improvement from baseline in BCVA (time frame: From baseline to Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06743646, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.