A Preliminary Clinical Study on the Safety and Efficacy of the Gene Replacement Drug ZVS106e in the Treatment of Hereditary Retinal Degeneration (IRDs) Caused by ABCA4 Biallelic Mutations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Evaluate the safety and tolerability of subretinal injection of ZVS106e solution
研究概览
简要总结
To evaluate the preliminary safety of monocular and single subretinal injection of ZVS106e injection in the treatment of patients with hereditary retinal degeneration (ABCA4-IRDS) caused by ABCA4 biallelic mutations.
详细描述
The main research objective: To evaluate the preliminary safety of single subretinal injection of ZVS106e injection in one eye for patients with hereditary retinal degeneration (ABCA4-IRDS) caused by biallelic mutations in ABCA4. Secondary research objective: To preliminarily explore the clinical efficacy of ZVS106e injection in the treatment of patients with hereditary retinal degeneration (ABCA4-IRDS) caused by ABCA4 biallelic mutations. The purpose of the exploratory study is to evaluate the improvement of retinal structure and visual function in non-injection eyes compared to the baseline.
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
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥8 years old;
- •Patients diagnosed with hereditary retinal degeneration caused by ABCA4 biallelic mutations through genetic testing, and without other ophthalmic genetic diseases;
- •The target eye must meet the following requirements: the best corrected visual acuity is 0.5 to 2.0 LogMAR (including 0.5 and 2.0 LogMAR, equivalent to the decimal visual acuity index up to 0.3);
- •The subject and his or her spouse agree to take effective contraceptive measures during the trial period and for at least one year after administration.
- •Voluntarily participate in clinical trials and sign informed consent forms, and be able to complete all trial processes as required by the protocol.
排除标准
- •The researchers determined that the target eye currently has or has previously had other macular lesions such as retinal schisis or epiretinal membrane. Or have other eye diseases that may hinder the surgery or interfere with the interpretation of the study endpoint;
- •Having received drug treatment that may affect the observation of the trial within the three months prior to screening;
- •The target eye has undergone the following intraocular surgeries: retinal repositioning and vitrectomy;
- •There are known eye/visual diseases, disorders or lesions that cause or are related to vision loss, or whose related treatments or therapies are known to cause or are related to vision loss;
- •Having suffered from a viral infectious disease that may affect the efficacy and safety evaluation of the investigational drug or having received an antiviral vaccine within one month prior to enrollment;
- •Systemic medications that are currently in use or may be required to cause eye toxicity, such as psoralen, risselinic acid or tamoxifen, etc.
- •Known to be allergic to the drugs planned to be used in the study;
- •Suffering from poorly drug-controlled hypertension: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg;
- •The following laboratory test abnormalities have clinical significance:
- •Liver function: Chronic liver disease, elevation of ALT or AST >2 times the upper limit of the normal value; Those with abnormal coagulation function (prothrombin time ≥ 3 seconds above the upper limit of the normal value, activated partial thromboplastin time ≥ 10 seconds above the upper limit of the normal value); Serum virological examination: Positive for active hepatitis B, hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or syphilis antibody;
- •There is any past or current medical history that may affect the safety of the trial or the in vivo process of the drug, especially a history of diseases such as cardiovascular, liver, kidney, endocrine, digestive tract, lung, nervous, hematological, tumor, immune or metabolic disorders that the investigators consider to have clinical significance;
- •Those who have participated in any clinical trials of drugs or medical devices within the three months prior to screening;
- •Pregnant or lactating women; According to the researcher's judgment, those who are deemed unsuitable to participate in this clinical trial for other reasons
研究组 & 干预措施
Single arm
All patients enrolled in the study will receive a single subretinal injection of ZVS106e in one eye
干预措施: ZVS106e (Drug)
结局指标
主要结局
Evaluate the safety and tolerability of subretinal injection of ZVS106e solution
时间窗: 52 weeks post-treatment
Types, severity, and incidence of adverse events (AE) and serious adverse events (SAE) in the eyes and throughout the body within 52 weeks post-treatment, including dose-limiting toxicities (DLT) during the dose escalation phase.
次要结局
- Change from Baseline in Visual function metrics(52 weeks post-treatment)
- Change from Baseline in OCT(52 weeks post-treatment)
- Change from baseline in best-corrected visual acuity (BCVA)(52 weeks post-treatment)
- Change from Baseline in Fundus autofluorescence (FAF)(52 weeks post-treatment)
- Change from Baseline in multi-luminance mobility test (MLMT)(52 weeks post-treatment)
研究者
Qingjiong Zhang
PI
Zhongshan Ophthalmic Center, Sun Yat-sen University