A Single-arm, Open-label Exploratory Clinical Study to Assess the Preliminary Safety of the Gene Editing Drug ZVS203e for the Management of Retinitis Pigmentosa Caused by Mutations in the RHO Gene
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Incidence of adverse events (AEs）
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and efficacy of a single escalating doses of ZVS203e administered via subretinal injection in participants with RP caused by RHO site-specific gene mutation (RHO-RP).
详细描述
This is a single-arm, open-label, single ascending dose study of ZVS203e in participants with RHO-RP. Up to 9 participants will be enrolled in this study. Safety, efficacy and vector shedding characteristics of ZVS203e are then measured.
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
- •Patients with clinical diagnosis of Retinitis Pigmentosa (RP) (age ≥ 18 years) ;
- •Genetic test confirmed to carry a fix mutation of RHO and carry no pathogenic mutations of other ophthalmic genetic diseases;
- •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) ;
- •Agree to take effective contraceptive measures from the beginning of the study to 1 year after the administration;
- •5.Willingness to adhere to protocol as evidenced by written informed consent;
排除标准
- •Existing or pre-existing of macular lesions such as retinoschisis or macular membrane, or other eye conditions interfering with the surgery or the interpretation of the clinical endpoint, in the investigators' opinion;
- •The study eye has been treated with other drugs within 3 months that could affect the evaluation of the investigational drug;
- •The study eye has been treated with the following intraocular procedures: retinal detachment surgery, vitrectomy;
- •The presence of an ocular/visual disease, disorder or lesion known to cause, or to be associated with, vision loss, or whose associated treatment or therapy is known to cause, or to be associated with, vision loss；
- •Currently taking or may require systemic medications that can cause ocular toxicity, such as psoralen, risedronate, or tamoxifen;
- •Known allergy to the drug planned for use in the study；
- •7.Those with the following laboratory abnormalities which are clinically significant: Liver function: chronic liver disease, ALT increased >2 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;
- •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;
- •Any other conditions which leads the investigator to determine the participant is unsuitable for this study.
研究组 & 干预措施
Dose escalation
Three 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 ZVS203e at Day 0. Cohort 2: Subretinal administration of a single medium dose ZVS203e at Day 0. Cohort 3: Subretinal administration of a single high dose ZVS203e at Day 0.
干预措施: ZVS203e (Drug)
结局指标
主要结局
Incidence of adverse events (AEs）
时间窗: Baseline up to Week 52
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 (SAEs)
时间窗: Baseline up to Week 52
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.
次要结局
- Mean change from baseline in BCVA after ZVS203e treatment(Baseline up to Week 52)
- Change from Baseline in multi-luminance mobility test (MLMT)(Baseline up to Week 52)
- Change from Baseline in retinal thickness(Baseline up to Week 52)
- Change from Baseline in fundus autofluorescence (FAF)(Baseline up to Week 52)
- Change from Baseline in color vision(Baseline up to Week 52)
- Change from Baseline in mfERG(Baseline up to Week 52)
- Change from Baseline in visual field(Baseline up to Week 52)
- Change from Baseline in contrast sensitivity(Baseline up to Week 52)
- Change from Baseline in NEI VFQ-25 total score(Baseline up to Week 52)