Safety Study of rAAV2/8-hCYP4V2 in Patients With Bietti's Crystalline Dystrophy (BCD)

NCT04722107 | Unknown Early Phase 1 FDA Drug

• 1 other identifier: ZVS101e-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objectives: To evaluate the safety of rAAV2/8-hCYP4V2 gene replacement therapy drug administered as a single subretinal injection in patients with Bietti's Crystalline Dystrophy (BCD). Secondary Objectives: To preliminarily explore the clinical effectiveness of rAAV2/8-hCYP4V2 gene replacement therapy drugs.

Conditions

Bietti's Crystalline Dystrophy

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  Incidence of adverse events, vital signs, physical examination, ophthalmic 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.

  24 months

• Incidence of serious adverse events

  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

  24 months

• Clinically important changes from baseline after ZVS101e treatment

  Clinically important changes including abnormal physical examinations, vital signs, ECG, laboratory findings (chemistry, hematology, urinalysis) and ophthalmologic findings (BCVA, slit lamp examination, ophthalmoscopy, IOP, funds photography, FAF, OCT, OCTA).

  24 months

Secondary Outcomes (10)

• Mean change from baseline in BCVA after ZVS101e treatment

  24 months

• Change from Baseline in visual field

  24 months

• Change from Baseline in contrast sensitivity

  24 months

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

  24 months

• Change from Baseline in OCTA

  24 months

Study Arms (1)

Single arm

EXPERIMENTAL

All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye

Drug: rAAV2/8-hCYP4V2

Interventions

rAAV2/8-hCYP4V2 DRUG

rAAV2/8-hCYP4V2 is developed by Chigenovo Co., Ltd., it contains recombinant adeno-associated virus serotype 8 (rAAV8) vectors which carry human CYP4V2 gene

Also known as: ZVS101e, rAAV8-hCYP4V2

Single arm

Eligibility Criteria

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

You may qualify if:

• \) Age ≥ 18 years old at the time of informed consent ;
• \) Patients with a clinical diagnosis of Bietti's crystalline dystrophy (BCD);
• \) Genetic test confirmed to carry two pathogenic variants of CYP4V2;
• \) Agree to take effective contraceptive measures from the beginning of the study to 2 year after the administration;
• \) Voluntarily participate in this clinical trial and have signed the informed consent form.

You may not qualify if:

• \) Patients lack sufficient retinal photoreceptors, retinal photoreceptors less than 1 optic disc area or retinal thickness less than 100 μm in the macula；
• \) Existing or pre-existing of choroidal neovascular (CNV) lesions that were secondary to BCD, or other eye conditions interfering（ (e.g., high refractive error, retinal vasculitis, etc.) ） that may prevent surgery or interfere with the interpretation of the study endpoint;
• \) Prior use of medicines which may affect the experimental observation within the 6 months before screening (such as ranibizumab, bevacizumab, aflibercept, conbercept)；
• \) Prior intraocular surgery in the target eye (e.g. PDT, pars plana vitrectomy, retinal laser therapy )
• \) Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen；
• \) Allergic constitution (such as those who are allergic to two or more drugs and foods);
• \) Abnormal physical examination, vital signs, laboratory tests (blood routine, urine routine, blood biochemistry, coagulation function, immunological examination, female blood pregnancy), 12-lead ECG, X-ray chest radiograph findings with any clinically significant abnormality, and where participation in this study may increase the subject's risk or interfere with data interpretation as assessed by the investigator；
• \) 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；
• \) Participation in any medicine or medical device clinical trials within 3 months prior to enrollment;;
• \) Neutralizing antibodies to rAAV\> 1:1000 by immunologic test;
• \) For females in pregnancy or lactation period;
• )Carrying other ophthalmic pathogenic mutations
• \) Any other conditions which leads the investigator to determine the participant is unsuitable for this study.

Sponsors & Collaborators

• Beijing Tongren Hospital: lead

Study Sites (1)

Beijing Tongren Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (1)

• 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

MeSH Terms

Conditions

Bietti Crystalline Dystrophy

Study Officials

• wenbin Wei, Doctor

  Vice President of Beijing Tongren Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

wenbin Wei, Doctor

CONTACT

13701255115; tr_weiwenbin@163.com

xiuli Zhao, Doctor

CONTACT

18811612056; xiulizhao@medmail.com.cn

Study Design

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

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: January 25, 2021
• Study Start: April 21, 2021
• Primary Completion: January 25, 2024
• Study Completion: April 29, 2024
• Last Updated: June 5, 2023

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)