AzTrials
AzTrials

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.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

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:
Show all 18Show fewer
  • 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

Other trials in China

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.

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 groups in NCT05832684
Study groupRoleWhat they receive
ExperimentalExperimentalDose 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.

  1. 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

  2. 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

  3. 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)

  1. 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

  2. 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

  3. 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

  4. 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

  5. Change from Baseline in retinal thickness

    Retinal thickness will be assessed for both eyes using OCT.

    Measured: Up to day 180

  6. 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

  7. 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.

  1. First posted27 Apr 2023
  2. Study start20 Feb 2023
  3. Primary completion23 Jul 2024
  4. Study completionDec 2028 (estimated)

Resources

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)
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 40482806

  • 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.

    PubMed 42025802

  • 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.

    PubMed 35925866

  • 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.

    PubMed 38653979

  • 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 41520174

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 uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in