Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-VMD2-hMERTK) Gene Vector to Patients With Retinal Disease Due to MERTK Mutations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Systemic and Ocular Safety
研究概览
简要总结
This study was to assess the safety of gene transfer via subretinal administration of rAAV2-VMD2-hMERTK in subjects with MERTK-associated retinitis pigmentosa (RP).
详细描述
In this phase I open-label, dose-escalation trial, one eye of each patient (the worse-seeing eye in five subjects) will receive a submacular injection of the subretinal rAAV2-VMD2-hMERTK. Patients will be followed daily for 10 days and then at 30, 60, 90, 180, 270, 365, 540, and 730 days post-injection. Data will be collected on (1) full ophthalmologic examination including best-corrected VA, intraocular pressure, color fundus photographs, macular spectral-domain optical coherence tomography, and full-field stimulus threshold test (FST) in both the study and fellow eyes; (2) systemic safety data including CBC, liver, and kidney function tests, coagulation profiles, urine analysis, AAV antibody titers, peripheral blood PCR and ASR measurement; and (3) listing of ophthalmological or systemic adverse effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MERTK-associated retinal disease;
- •VA: 20/100 or less in worse eye
- •Ability to perform tests of visual and retinal function;
- •Good general health based on a complete physical examination and hematology and chemistry studies performed at a pre-treatment evaluation;
- •Ability to comply with research procedures;
排除标准
- •Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or surgical complications (for example, glaucoma, corneal or lenticular opacities);
- •Complicating systemic diseases (such as medical conditions causing immunosuppression) that would preclude the gene transfer, ocular surgery or known sensitivity or allergy to medications planned for use in the peri-operative period;
- •Use of anti-platelet agents that may alter coagulation within 7 days prior to study agent administration;
- •Use of immunosuppressive medications;
- •Pregnancy or breastfeeding;
- •Individuals (males and females) of childbearing potential who are unwilling to use effective contraception for 1 year following agent administration and barrier contraception for 3 months following agent administration;
- •Any other condition that would prevent a subject from completing follow-up examinations during the course of the study and that, in the opinion of the investigator, makes the subject unsuitable for the study.
- •Current, or recent (within the past 30 days, or 10 half lives of the drug) participation, in any other research protocol involving investigational agents or therapies.
- •Recent (within past 6 months) receipt of an investigational biologic therapeutic agent.Subjects will not be excluded based on their gender, race or ethnicity.
结局指标
主要结局
Systemic and Ocular Safety
时间窗: 2 years
Detailed history \& physical exam were obtained at baseline visit and each post-injection protocol visit searching for systemic adverse events. Included were electrocardiogram, chest X-ray, complete blood count \& differential, prothrombin time \& INR, partial thromboplastin time, serum electrolytes, full serum chemistries including liver and renal function, urinalysis; serum antibody titers to AAV2 capsid components and antigen-specific reactivity (ASR) assays; blood analysis by DNA PCR to detect vector spread. Ophthalmic safety monitored changes from baseline included 1) corneal abnormalities, afferent pupillary defect, intraocular inflammation, cataract \& intraocular pressure changes; 2) retinal changes based on fundus photos; 3) Macular SD-OCT changes in Central macular (CMT) and central foveal thickness (CFT) measurements when patient fixation allowed it, and 4) full field stimulus threshold (FST) to detect any retinal toxicity .
次要结局
- Visual Acuity Measurement(2 years and up to 5 years)
- Full-field Stimulus Threshold Testing (FST).(2 years)
- Central Foveal Thickness (CFT) on Optical Coherence Tomography (OCT).(2 years)
- Central Macular Thickness (CMT) on Optical Coherence Tomography (OCT).(2 years)