Safety Trial of rAAV2/8-hCYP4V2 Gene Replacement Therapy Drug Administered as a Single Subretinal Injection in Patients With Bietti's Crystalline Dystrophy (BCD)
试验速览
- 阶段
- 早期 1 期
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
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.
详细描述
This is a single-arm, open-label, and single-center study of ZVS101e in patients with BCD. A total of 12 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
- •Meet the following target eye selection criteria： Best corrected visual acuity between 2.3 LogMAR and 0.5 LogMAR (including 2.3 LogMAR and 0.5 LogMAR, equivalent to Snellen visual acuity of hand move to 20/63); No refractive media clouding affecting fundus examination, visual examination and retinal function examination; The eye with the poorer visual acuity of the two eyes of the subject is the target eye. Note: For all subjects, only one eye will be used as the "target eye". If both eyes meet the inclusion criteria and the visual acuity is comparable, the target eye will be determined medically by the investigator.
- •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.
排除标准
- •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.
研究组 & 干预措施
Single arm
All patients enrolled in the study will receive a single subretinal injection of ZVS101e in one eye
干预措施: rAAV2/8-hCYP4V2 (Drug)
结局指标
主要结局
Incidence of adverse events
时间窗: 24 months
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.
Incidence of serious adverse events
时间窗: 24 months
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
Clinically important changes from baseline after ZVS101e treatment
时间窗: 24 months
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).
次要结局
- Change from Baseline in contrast sensitivity(24 months)
- Change from Baseline in multi-luminance mobility test (MLMT)(24 months)
- Change from Baseline in retinal thickness(24 months)
- Mean change from baseline in BCVA after ZVS101e treatment(24 months)
- Change from Baseline in visual field(24 months)
- Change from Baseline in microperimetry(24 months)
- Change from Baseline in mfERG(24 months)
- Change from Baseline in OCTA(24 months)
- Change from Baseline in NEI VFQ-25 total score(24 months)
- Change from Baseline in fundus autofluorescence (FAF)(24 months)