Bietti's Crystalline DystrophyPhase 1/2NCT05832684
Safety and Efficacy of ZVS101e in Patients With Bietti 's Crystalline Dystrophy
A Phase 1/2 study testing ZVS101e in people with Bietti's Crystalline Dystrophy, run by Chigenovo Co., Ltd at 3 sites in China.
Trial summary
The purpose of this study was to evaluate the safety and efficacy of ZVS101e administered by subretinal injection in subjects with Bietti's crystalline dystrophy (BCD) and to select the optimal effective dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bietti's 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
- 24 participants
- Where
- 3 sitesChina
- Study dates
- 20 Feb 2023to Dec 2028
- Phase
- Phase 1/2
- 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
- 1. Fully understand the purpose and requirements of this trial, voluntarily participate in the clinical trial, sign the informed consent form, and be able to complete the whole trial processes as required by the protocol;
- 2. Patients with clinical diagnosis of Bietti's crystalline dystrophy (BCD) (age ≥ 18 years) (including the critical value, and the age is based on the time of signing the informed consent form);
- 3. Genetic test confirmed to carry two pathogenic variants of CYP4V2 and carry no pathogenic mutations of other ophthalmic genetic diseases;
- 4. The study eye must meet the following requirements: Best-corrected visual acuity between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR).
Who cannot join
- 1. Subjects with insufficient viable retinal cells, or macular retinal less than 100 μm thick;
- 2. Pre-existing eye conditions in the study eye that the investigator determines could interfere with ocular evaluation, preclude surgery, interfere with interpretation of study endpoints or pose surgical complications;
- 3. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
- 4. The study eye has been treated with other drugs within 3 months that could affect the evaluation of the investigational drug (such as ranibizumab, bevacizumab, aflibercept, conbercept);
- 5. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
- 6. Those with the following laboratory abnormalities which are clinically significant:
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- Liver function: chronic liver disease, ALT increased > 2 times the upper limit of normal;
- Hypertension, mean SBP ≥ 160 mmHg or mean DBP ≥ 100 mmHg;
- Coagulation function (prothrombin time ≥ upper limit of normal (3 seconds' longer), activated partial thromboplastin time ≥ upper limit of normal (10 seconds' longer));
- Serum virology test: Active hepatitis B, hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab) or syphilis antibody positive;
- 7. Patients with rAAV8 neutralizing antibody titer ≥ 1:1000;
- 8. Complicating systemic diseases (such as medical conditions causing immunosuppression) that would preclude the gene transfer, ocular surgery and drug in vivo activity;
- 9. Known drug allergy to the drug planned to be used in the study;
- 10. Patients who cannot communicate or cooperate with medical staff due to neurological, mental illness or language disorder, which affects patient compliance;
- 11. Treatment of either eye with gene therapy drugs for BCD and other ocular diseases, including but not limited to other viral vector gene therapies, mRNA therapy, etc.;
- 12. Has or has had a systemic immune-compromising disease;
- 13. Subjects of reproductive age without any effective contraception and female subjects who have tested positive for pregnancy or are lactating at screening or baseline;
- 14. A condition that, in the opinion of the investigator, would preclude participation in the study.
Trial locations and contacts
3 sites in 1 country.
China3 sites
Peking University Third Hospital
Beijing, Beijing Municipality, 100191
West China Hospital, Sichuan University
Chengdu, Sichuan
Tianjin Medical University Eye Hospital
Tianjin, Tianjin Municipality, 300392
About this study
Official title: A Phase I/II Clinical Study to Evaluate the Safety and Efficacy of ZVS101e Administered as a Single Monocular Subretinal Injection in Subjects With Bietti's Crystalline Dystrophy (BCD)
The purpose of this study was to evaluate the safety and efficacy of ZVS101e administered by subretinal injection in subjects with Bietti's crystalline dystrophy (BCD) and to select the optimal effective dose.
Read the detailed description
This is a single-arm, open-label, and multi-center study of ZVS101e in patients with BCD. Up to 24 subjects are expected to be enrolled. Each participant will receive ZVS101e by subretinal injection in one eye on a single occasion. Safety, efficacy and vector shedding characteristics of ZVS101e are then measured over 180 days. Participants will subsequently enter a long-term follow-up study over a 4.5-year period.
- Conditions
- Bietti's Crystalline Dystrophy
- Being tested
- ZVS101e
- 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 rAAV2/8-hCYP4V2, rAAV8-hCYP4V2, AAV8-hCYP4V2
ZVS101e contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human wild type CYP4V2 gene.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Dose escalation and expansion of ZVS101e. All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye. Receives: Drug: ZVS101e |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of ocular and systemic adverse events (AEs) after ZVS101e treatment
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: Up to day 180
Incidence of ocular and systemic serious adverse events (SAEs) after ZVS101e treatment
A serious adverse event (SAE) is any untoward medical occurrence at any dose that leading to the following:
Results in death; Life-threatening, refers to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe; Significant or permanent disability/incapacity, where disability refers to a serious disruption and damage of a person's ability to perform normal life functions; Requires inpatient hospitalization or prolongation of existing hospitalization; Congenital anomaly or birth defect; Other medically important events.
Measured: Up to day 180
Mean change from baseline in BCVA (LogMAR)
BCVA of both eyes will be assessed using the early treatment of diabetic retinopathy study (ETDRS) chart.
Measured: Up to day 180
Secondary outcomes (7)
Change from Baseline in visual field
Visual field will be assessed by Humphrey perimetry, changes in retinal light sensitivity will be analyzed.
Measured: Up to day 180
Change from Baseline in contrast sensitivity
Change from baseline in contrast sensitivity at all spatial frequency will be measured using the CSV-1000E instrument.
Measured: Up to day 180
Change from Baseline in microperimetry
Microperimetry will be measured using MP-3，changes in retinal sensitivity (dB) will be analyzed.
Measured: Up to day 180
Change from Baseline in mfERG
The measurement will be performed based on the standards of international society for clinical electrophysiology of vision (ISCEV). Response Amplitude Density will be analyzed.
Measured: Up to day 180
Change from Baseline in retinal thickness
Retinal thickness will be assessed for both eyes using OCT.
Measured: Up to day 180
Change from Baseline in NEI VFQ-25 total 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: Up to day 180
Change from Baseline in color vision
Subjects' color vision was classified and graded by having them identify the pictures within Color Vision Examination Plates.
Measured: Up to day 180
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2023
- Study start20 Feb 2023
- Primary completion23 Jul 2024
- Study completionDec 2028 (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's Crystalline 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chigenovo Co., Ltd
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Xiaorong Li, MD, Principal investigator, Tianjin Medical University Eye Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05832684
- Sponsor's protocol ID
- ZYA-2022-001
- Status last verified
- Jun 2026
- First submitted
- 2 Apr 2023
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- 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, 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 38653979Yang 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 41520174
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Study to Evaluate the Safety and Efficacy of ZVS101e Administered as a Single Monocular Subretinal Injection in Subjects With Bietti's Crystalline Dystrophy (BCD)
- ClinicalTrials.gov ID
- NCT05832684
- Acronym / sponsor ID
- ZYA-2022-001
- Conditions
- Bietti's Crystalline Dystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Chigenovo Co., LtdResearch network
- Study start
- 20 Feb 2023 (actual)
- Primary completion
- 23 Jul 2024 (actual)
- Study completion
- Dec 2028 (estimated)
- First posted
- 27 Apr 2023 (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.
The purpose of this study was to evaluate the safety and efficacy of ZVS101e administered by subretinal injection in subjects with Bietti's crystalline dystrophy (BCD) and to select the optimal effective dose.
Detailed description
This is a single-arm, open-label, and multi-center study of ZVS101e in patients with BCD. Up to 24 subjects are expected to be enrolled. Each participant will receive ZVS101e by subretinal injection in one eye on a single occasion. Safety, efficacy and vector shedding characteristics of ZVS101e are then measured over 180 days. Participants will subsequently enter a long-term follow-up study over a 4.5-year period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: ZVS101eDose escalation and expansion of ZVS101e. All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 1. Fully understand the purpose and requirements of this trial, voluntarily participate in the clinical trial, sign the informed consent form, and be able to complete the whole trial processes as required by the protocol;
- 2. Patients with clinical diagnosis of Bietti's crystalline dystrophy (BCD) (age ≥ 18 years) (including the critical value, and the age is based on the time of signing the informed consent form);
- 3. Genetic test confirmed to carry two pathogenic variants of CYP4V2 and carry no pathogenic mutations of other ophthalmic genetic diseases;
- 4. The study eye must meet the following requirements: Best-corrected visual acuity between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR).
Key exclusion criteria (18 listed)
- 1. Subjects with insufficient viable retinal cells, or macular retinal less than 100 μm thick;
- 2. Pre-existing eye conditions in the study eye that the investigator determines could interfere with ocular evaluation, preclude surgery, interfere with interpretation of study endpoints or pose surgical complications;
- 3. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
- 4. The study eye has been treated with other drugs within 3 months that could affect the evaluation of the investigational drug (such as ranibizumab, bevacizumab, aflibercept, conbercept);
- 5. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
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: rAAV2/8-hCYP4V2, rAAV8-hCYP4V2, AAV8-hCYP4V2ZVS101e contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human wild type CYP4V2 gene. | Drug | Experimental |
Primary outcome
Incidence of ocular and systemic adverse events (AEs) after ZVS101e treatment
Time frame: Up to day 180
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.
Incidence of ocular and systemic serious adverse events (SAEs) after ZVS101e treatment
Time frame: Up to day 180
A serious adverse event (SAE) is any untoward medical occurrence at any dose that leading to the following: Results in death; Life-threatening, refers to an event in which the patient is at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe; Significant or permanent disability/incapacity, where disability refers to a serious disruption and damage of a person's ability to perform normal life functions; Requires inpatient hospitalization or prolongation of existing hospitalization; Congenital anomaly or birth defect; Other medically important events.
Mean change from baseline in BCVA (LogMAR)
Time frame: Up to day 180
BCVA of both eyes will be assessed using the early treatment of diabetic retinopathy study (ETDRS) chart.
7 secondary outcomes
Change from Baseline in visual field
Time frame: Up to day 180
Change from Baseline in contrast sensitivity
Time frame: Up to day 180
Change from Baseline in microperimetry
Time frame: Up to day 180
Change from Baseline in mfERG
Time frame: Up to day 180
Change from Baseline in retinal thickness
Time frame: Up to day 180
Change from Baseline in NEI VFQ-25 total score
Time frame: Up to day 180
Change from Baseline in color vision
Time frame: Up to day 180
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 17 Jun 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 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.
- Results publication: 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.
- 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.
Xiaorong Li, MD principal investigator
Tianjin Medical University Eye Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZVS101e in people with Bietti's Crystalline Dystrophy, run by Chigenovo Co., Ltd at 3 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 4 inclusion and 18 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 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Incidence of ocular and systemic adverse events (AEs) after ZVS101e treatment (time frame: Up to day 180). The study lists 3 primary outcomes in all. 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 NCT05832684, 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 17 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.