Safety and Efficacy of ZVS101e in Patients With Bietti 's Crystalline Dystrophy

NCT05832684 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ZYA-2022-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Bietti's Crystalline Dystrophy

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to day 180

Secondary Outcomes (7)

• Change from Baseline in visual field

  Up to day 180

• Change from Baseline in contrast sensitivity

  Up to day 180

• Change from Baseline in microperimetry

  Up to day 180

• Change from Baseline in mfERG

  Up to day 180

• Change from Baseline in retinal thickness

  Up to day 180

Other Outcomes (1)

• Change from Baseline in multi-luminance mobility test (MLMT)

  Up to day 180

Study Arms (1)

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.

Drug: ZVS101e

Interventions

ZVS101e DRUG

ZVS101e contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human wild type CYP4V2 gene.

Also known as: rAAV2/8-hCYP4V2, rAAV8-hCYP4V2, AAV8-hCYP4V2

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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;
• \. 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);
• \. Genetic test confirmed to carry two pathogenic variants of CYP4V2 and carry no pathogenic mutations of other ophthalmic genetic diseases;
• \. 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).

You may not qualify if:

• \. Subjects with insufficient viable retinal cells, or macular retinal less than 100 μm thick;
• \. 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;
• \. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
• \. 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);
• \. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
• \. Those with the following laboratory abnormalities which are clinically significant:
• 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;
• \. Patients with rAAV8 neutralizing antibody titer ≥ 1:1000;
• \. Complicating systemic diseases (such as medical conditions causing immunosuppression) that would preclude the gene transfer, ocular surgery and drug in vivo activity;
• \. Known drug allergy to the drug planned to be used in the study;
• \. Patients who cannot communicate or cooperate with medical staff due to neurological, mental illness or language disorder, which affects patient compliance;
• \. 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.;

Sponsors & Collaborators

• Chigenovo Co., Ltd: lead

Study Sites (3)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

Tianjin Medical University Eye Hospital

Tianjin, Tianjin Municipality, 300392, China

Location

Related Publications (2)

• 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.

  PMID: 35925866 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.

  PMID: 38653979 BACKGROUND

MeSH Terms

Conditions

Bietti Crystalline Dystrophy

Study Officials

• Xiaorong Li, MD

  Tianjin Medical University Eye Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2023
• First Posted: April 27, 2023
• Study Start: February 20, 2023
• Primary Completion: December 1, 2024
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)