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

NCT ID: NCT05714904

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-23
• Study Completion Date: 2025-03-31

Brief 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).

Detailed Description

This is a single-arm, open-label, and single-center study of ZVS101e in patients with BCD. A total of 6 participants will be enrolled. A retinal surgeon will administer the vector by subretinal injection. Safety, efficacy and vector shedding characteristics of ZVS101e are then measured over 2 years.

Conditions

Bietti's Crystalline Dystrophy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

2 cohorts of 3 patients each. All the patients enrolled in the study will receive a single subretinal injection in one eye.

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.

Group Type: EXPERIMENTAL

ZVS101e

Intervention Type: DRUG

ZVS101e is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene.

Interventions

ZVS101e

ZVS101e is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene.

Intervention Type: DRUG

Other Intervention Names

rAAV2/8-hCYP4V2; rAAV8-hCYP4V2

Eligibility Criteria

Inclusion Criteria

1. Willingness to adhere to protocol as evidenced by written informed consent;

2. Patients with clinical diagnosis of Bietti's crystalline dystrophy (BCD) (age ≥ 18 years) (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. Agree to use reliable barrier contraception for 2 year after administration of ZVS101e;

5. The study eye must meet the following requirements: BCVA between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR); No refractive medium turbidity that affects fundus examination; Visible photoreceptor (outer nuclear) layer on a standard optical coherence tomography (OCT) scan.

Exclusion Criteria

1. Lack of sufficient viable retinal cell. Specifically, if indirect ophthalmoscopy reveals less than I disc area of retina which is not involved by complete retinal degeneration, these eyes will be excluded. In addition, in eyes where OCT scans of sufficient quality can be obtained, areas of retina with thickness measurements less than 100 μm, or absence of neural retina, will not be targeted for delivery of AAV2-hCYP4V2;

2. Existing or pre-existing of choroidal neovascular (CNV) lesions that were secondary to BCD, or other eye conditions interfering with the surgery or the interpretation of the clinical endpoint, in the investigators' opinion;

3. 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);

4. The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;

5. Pre-existing eye conditions that the investigator evaluates could interfere with ocular evaluation, preclude surgery, interfere with interpretation of study endpoints or surgical complications (such as glaucoma, high refractive error, diabetes retinopathy or retinal vasculitis );

6. Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;

7. Patient with allergic constitution (such as those allergic to two or more drugs and food);

8. Those with the following laboratory abnormalities which are clinically significant:

Liver function: chronic liver disease, ALT increased >3 times the upper limit of normal; With uncontrolled hypertension, mean systolic blood pressure ≥ 160 mmHg or mean diastolic blood pressure ≥ 100 mmHg; With uncontrolled diabetes, HbA1c>10%; Patients with abnormal 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; Abnormality of tumor markers (alpha fetoprotein, carcinoembryonic antigen, CA125 carbohydrate antigen, CA153 carbohydrate antigen, CA199 carbohydrate antigen)

9. Having any past or present medical history that may affect the safety of the trial or the in vivo process of the drug, especially the medical history of cardiovascular, hepatic, renal, endocrine, gastrointestinal, pulmonary, neurological, hematological, oncologic, immunological or metabolic disorders and others that are thought clinically significant by the investigator, such as diabetes, severe cardiac failure (New York Heart Association Class III and IV);

10. Participation in any medicine or medical device clinical trials within 3 months prior to enrollment;

11. Neutralizing antibodies to rAAV> 1:1000 by immunologic test;

12. For females in pregnancy or lactation period;

13. Any other conditions which leads the investigator to determine the participant is unsuitable for this study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University Third Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hongliang Dou, MD

Role: PRINCIPAL_INVESTIGATOR

Peking University

Locations

Peking University Third Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hongliang Dou, MD

Role: CONTACT

douhongliang3736@sina.com

010-82266563

Xuefeng Feng, PhD

Role: CONTACT

xue168feng@sina.com

Facility Contacts

Hongliang Dou, MD

Role: primary

douhongliang3736@sina.com

010-82266563

References

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.

Reference Type: BACKGROUND

PMID: 35925866 (View on PubMed)

Other Identifiers

ZVS101e-01

Identifier Type: -

Identifier Source: org_study_id