Bietti's Crystalline DystrophyEarly Phase 1NCT05714904
Safety and Tolerability of ZVS101e in Patients With Bietti 's Crystalline Dystrophy
A Early Phase 1 study testing ZVS101e in people with Bietti's Crystalline Dystrophy, run by Peking University Third Hospital at 1 site in China.
Trial summary
The purpose of the study is to evaluate the safety and tolerability of an adeno-associated virus vector expressing CYP4V2 in patients with Bietti's crystalline dystrophy (BCD). This is a single-arm, open-label, and single-center study. 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
- 9 participants
- Where
- 1 siteChina
- Study dates
- 23 Sep 2022to Dec 2027
- Phase
- Early Phase 1
- 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
- Subjects who meet all of the following inclusion criteria may be eligible to participate in this study:
- The subject voluntarily signs the written informed consent form and is willing to comply with the long-term follow-up protocol and companion protocol;
- Clinically diagnosed with Bietti's crystalline dystrophy (BCD) (aged ≥ 18 years);
- Confirmed by genetic testing to carry biallelic mutations in the CYP4V2 gene, with no pathogenic mutations of other ophthalmic genetic diseases;
- The subject and their spouse agree to use highly effective barrier contraception during the trial and for 2 years after drug administration;
- The study eye must meet the following requirements:
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- Best-corrected visual acuity (BCVA) ≥ 0.5 LogMAR (equivalent to decimal visual acuity ≤ 0.3);
- No refractive media turbidity that affects fundus examination, and the subject must be able to undergo visual and retinal function assessments;
- Visible photoreceptor layer (outer nuclear layer) in the macular area on standard optical coherence tomography (OCT) scans.
- *Defination of the study eye: For all subjects, only one eye is designated as the "study eye" (i.e., the eye receiving treatment). If both eyes of a subject meet the inclusion criteria, the eye with poorer visual acuity is selected as the study eye. If both eyes are affected equally, the right eye is selected as the study eye.
Who cannot join
- Subjects meeting any of the following criteria will be excluded from the study:
- Insufficient viable retinal photoreceptors, as determined by OCT or ophthalmoscopy.
- The investigator determines that the study eye has or has had choroidal neovascularization (CNV) secondary to BCD.
- Received other treatments within 3 months prior to screening that could affect the evaluation of the investigational drug's results (e.g., ranibizumab, bevacizumab, aflibercept, conbercept, triamcinolone acetonide, steroids, etc.).
- The study eye has previously undergone intraocular surgeries, such as retinal reattachment surgery or vitrectomy.
- Presence of other ocular diseases that may interfere with the surgical procedure or complicate the interpretation of study endpoints or surgical complications (e.g., glaucoma, diabetic retinopathy, or retinal vasculitis).
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- Currently using, or potentially requiring, systemic medications known to cause ocular toxicity (e.g., psoralen, risedronate, or tamoxifen).
- History of hypersensitivity or allergic constitution (e.g., allergy to two or more drugs or foods).
- Clinically significant abnormal laboratory findings, including:
- Liver function: Chronic liver disease, or ALT elevation > 3 times the upper limit of normal (ULN).
- Uncontrolled hypertension, defined as mean systolic blood pressure (SBP) ≥ 160 mmHg or mean diastolic blood pressure (DBP) ≥ 100 mmHg.
- Uncontrolled diabetes mellitus, defined as HbA1c > 10%.
- Abnormal coagulation function, defined as prothrombin time (PT) ≥ ULN + 3 seconds, or activated partial thromboplastin time (aPTT) ≥ ULN + 10 seconds.
- Positive serology for Hepatitis B surface antigen (HBsAg), Hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or syphilis antibody.
- Abnormalities in tumor markers (alpha-fetoprotein, carcinoembryonic antigen, CA125, CA153, or CA199).
- Any past or present medical history that may affect the safety of the trial or the in vivo process of the drug, especially clinically significant cardiovascular, hepatic, renal, endocrine, gastrointestinal, pulmonary, neurological, hematological, oncologic, immunological, or metabolic disorders (e.g., severe heart failure [NYHA Class III and IV], cor pulmonale, etc.), as determined by the investigator.
- Participation in any drug or medical device clinical trial within 3 months prior to screening.
- Immunologic testing reveals neutralizing antibodies to rAAV > 1:1000.
- Pregnant or lactating women.
- Any other conditions that, in the investigator's opinion, render the participant unsuitable for this clinical trial.
Trial locations and contacts
1 site in 1 country.
China1 site
Peking University Third Hospital
Beijing, Beijing Municipality, 100191
About this study
Official title: An Exploratory Clinical Study on Single Subretinal Injection of ZVS101e (rAAV2/8-hCYP4V2) Into Eyes With Bietti's Crystalline Dystrophy (BCD)
The purpose of the study is to evaluate the safety and tolerability of an adeno-associated virus vector expressing CYP4V2 in patients with Bietti's crystalline dystrophy (BCD). This is a single-arm, open-label, and single-center study.
Read the detailed description
The investigational drug ZVS101e is administered as a single dose via subretinal injection.
The trial is divided into two stages. The first stage is a dose-escalation phase, enrolling subjects in a 3+3 design across two dose cohorts. The second stage is a dose-expansion phase, in which 3 to 6 additional subjects will be enrolled in the dose cohort demonstrating a more favorable safety and efficacy profile.
The duration of the study for each subject includes a screening period, a core follow-up period of 52 (±4) weeks, and a 1-year long-term safety follow-up.
- Conditions
- Bietti's Crystalline Dystrophy
- Being tested
- ZVS101e
- Keywords
- gene therapy, CYP4V2, BCD
- 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
ZVS101e is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene.
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | All the patients enrolled in the study will receive a single subretinal injection in one eye.
Stage1:Dose-Escalation 3 subjects will be enrolled in each of the 2 cohorts. Cohort 1: Subretinal administration of a single low dose ZVS101e at Day 0. Cohort 2: Subretinal administration of a single high dose ZVS101e at Day 0.
Stage 2: Dose Expansion 3 to 6 additional subjects will be enrolled into the cohort with superior safety and efficacy. Receives: Drug: ZVS101e |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Assessment (AEs/SAEs) at Week 52
Safety assessment (AEs/SAEs) in the injected eye over 52(±4) weeks post-ZVS101e injection.
Measured: Baseline up to Week 52
Safety Assessment (AEs/SAEs) at Week 104
Safety assessment (AEs/SAEs) in the injected eye over 104(±4) weeks post-ZVS101e injection.
Measured: Baseline up to Week 104
Secondary outcomes (8)
Mean Change from Baseline in BCVA
BCVA (LogMAR) of the injected eyes will be assessed to evaluate the improvement of visual acuity. Visual acuity testing will record changes in central visual acuity, defined as the ability to resolve standard optotype images. This assessment will be performed using the ETDRS visual acuity chart. The measured central visual acuity will be recorded directly as the number of ETDRS letters or converted to logMAR (logarithm of the minimum angle of resolution) scores to facilitate comparison.
Measured: Baseline up to Week 52
Immunogenicity Assessment
Cellular and humoral immunogenicity will be assessed.
Measured: Baseline up to Week 52
Vector Shedding
Vector DNA shedding in bilateral tear fluid and biodistribution in whole blood will be assessed.
Measured: Baseline up to Week 52
Change from Baseline in Retinal Thickness
Central retinal thickness and outer nuclear layer structure of the injected eye will be assessed for the injected eye using OCT.
Measured: Baseline up to Week 52
Change from Baseline in Visual Field
Visual field for the injected eye will be assessed by Humphrey perimetry.
Measured: Baseline up to Week 52
Change from Baseline in Contrast Sensitivity
Change from baseline in contrast sensitivity for the injected eye will be measured by the CSV-1000E instrument.
Measured: Baseline up to Week 52
Change from Baseline in Color Vision
Change from baseline in color vision will be assessed in the injected eye. Subjects' color vision was classified and graded by having them identify the pictures within Color Vision Examination Plates.
Measured: Baseline up to Week 52
Change from Baseline in mfERG
The mean change from baseline in mfERG waveform parameters will be assessed for the injected eye. The measurement will be performed based on the standards of international society for clinical electrophysiology of vision (ISCEV).
Measured: Baseline up 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 posted6 Feb 2023
- Study start23 Sep 2022
- Primary completion31 Jul 2025
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Bietti's Crystalline DystrophyStudies of the same condition, open and under way.
- More trials run by Peking University Third HospitalThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The trial is divided into two stages. The first stage is a dose-escalation phase, enrolling subjects in a 3+3 design across two dose cohorts. The second stage is a dose-expansion phase, in which 3 to 6 additional subjects will be enrolled in the dose cohort demonstrating a more favorable safety and efficacy profile. The duration of the study for each subject includes a screening period, a core follow-up period of 52 (±4) weeks, and a 1-year long-term safety follow-up.
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Third Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hongliang Dou, MD, Principal investigator, Peking University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05714904
- Sponsor's protocol ID
- ZVS101e-01
- Status last verified
- Sep 2026
- First submitted
- 13 Dec 2022
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41520174Wang 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 38653979Jia 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 35925866
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study on Single Subretinal Injection of ZVS101e (rAAV2/8-hCYP4V2) Into Eyes With Bietti's Crystalline Dystrophy (BCD)
- ClinicalTrials.gov ID
- NCT05714904
- Acronym / sponsor ID
- ZVS101e-01
- Conditions
- Bietti's Crystalline Dystrophy
- Keywords
- gene therapy, CYP4V2, BCD
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Peking University Third HospitalUniversity, hospital or other
- Study start
- 23 Sep 2022 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- Dec 2027 (estimated)
- First posted
- 6 Feb 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 the study is to evaluate the safety and tolerability of an adeno-associated virus vector expressing CYP4V2 in patients with Bietti's crystalline dystrophy (BCD). This is a single-arm, open-label, and single-center study.
Detailed description
The investigational drug ZVS101e is administered as a single dose via subretinal injection.
The trial is divided into two stages. The first stage is a dose-escalation phase, enrolling subjects in a 3+3 design across two dose cohorts. The second stage is a dose-expansion phase, in which 3 to 6 additional subjects will be enrolled in the dose cohort demonstrating a more favorable safety and efficacy profile.
The duration of the study for each subject includes a screening period, a core follow-up period of 52 (±4) weeks, and a 1-year long-term safety follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The trial is divided into two stages. The first stage is a dose-escalation phase, enrolling subjects in a 3+3 design across two dose cohorts. The second stage is a dose-expansion phase, in which 3 to 6 additional subjects will be enrolled in the dose cohort demonstrating a more favorable safety and efficacy profile. The duration of the study for each subject includes a screening period, a core follow-up period of 52 (±4) weeks, and a 1-year long-term safety follow-up.
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: ZVS101eAll the patients enrolled in the study will receive a single subretinal injection in one eye. Stage1:Dose-Escalation 3 subjects will be enrolled in each of the 2 cohorts. Cohort 1: Subretinal administration of a single low dose ZVS101e at Day 0. Cohort 2: Subretinal administration of a single high dose ZVS101e at Day 0. Stage 2: Dose Expansion 3 to 6 additional subjects will be enrolled into the cohort with superior safety and efficacy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects who meet all of the following inclusion criteria may be eligible to participate in this study:
- The subject voluntarily signs the written informed consent form and is willing to comply with the long-term follow-up protocol and companion protocol;
- Clinically diagnosed with Bietti's crystalline dystrophy (BCD) (aged ≥ 18 years);
- Confirmed by genetic testing to carry biallelic mutations in the CYP4V2 gene, with no pathogenic mutations of other ophthalmic genetic diseases;
- The subject and their spouse agree to use highly effective barrier contraception during the trial and for 2 years after drug administration;
Key exclusion criteria (20 listed)
- Insufficient viable retinal photoreceptors, as determined by OCT or ophthalmoscopy.
- The investigator determines that the study eye has or has had choroidal neovascularization (CNV) secondary to BCD.
- Received other treatments within 3 months prior to screening that could affect the evaluation of the investigational drug's results (e.g., ranibizumab, bevacizumab, aflibercept, conbercept, triamcinolone acetonide, steroids, etc.).
- The study eye has previously undergone intraocular surgeries, such as retinal reattachment surgery or vitrectomy.
- Presence of other ocular diseases that may interfere with the surgical procedure or complicate the interpretation of study endpoints or surgical complications (e.g., glaucoma, diabetic retinopathy, or retinal vasculitis).
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-hCYP4V2ZVS101e is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene. | Drug | Dose escalation |
Primary outcome
Safety Assessment (AEs/SAEs) at Week 52
Time frame: Baseline up to Week 52
Safety assessment (AEs/SAEs) in the injected eye over 52(±4) weeks post-ZVS101e injection.
Safety Assessment (AEs/SAEs) at Week 104
Time frame: Baseline up to Week 104
Safety assessment (AEs/SAEs) in the injected eye over 104(±4) weeks post-ZVS101e injection.
8 secondary outcomes
Mean Change from Baseline in BCVA
Time frame: Baseline up to Week 52
Immunogenicity Assessment
Time frame: Baseline up to Week 52
Vector Shedding
Time frame: Baseline up to Week 52
Change from Baseline in Retinal Thickness
Time frame: Baseline up to Week 52
Change from Baseline in Visual Field
Time frame: Baseline up to Week 52
Change from Baseline in Contrast Sensitivity
Time frame: Baseline up to Week 52
Change from Baseline in Color Vision
Time frame: Baseline up to Week 52
Change from Baseline in mfERG
Time frame: Baseline up 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 13 Oct 2026.
- 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 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.
- 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.
- 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.
Hongliang Dou, MD principal investigator
Peking University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing ZVS101e in people with Bietti's Crystalline Dystrophy, run by Peking University Third Hospital at 1 site 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 10 inclusion and 20 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 13 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 1 site 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Safety Assessment (AEs/SAEs) at Week 52 (time frame: Baseline up to Week 52). The study lists 2 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 NCT05714904, which also lists 3 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 13 Oct 2026.