An Open Label Phase 2 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Change in Best Corrected Visual Acuity From Baseline
研究概览
简要总结
Phase II gene therapy study, involving a total of 6 male patients with choroideremia. The study will be conducted at the Bascom Palmer Eye Institute, University of Miami. Patients will be required to attend a total of 11 study visits over a 24 month period with an additional 3 year follow-up.
详细描述
This is a Phase II, open label study involving patients with a clinical phenotype of choroideremia and a confirmed CHM genotype. Following consent, patients will be required to attend an initial screening visit (Visit 1). Within 2 weeks of the screening visit patients will undergo a surgical procedure (Visit 2) under general anesthesia which will include a standard vitrectomy, retinal detachment and administration of a subretinal injection of AAV2-REP1 (1x1011 genome particles). Patients will be required to attend a further 9 study visits (Visits 3-11) over a 24 month period for functional, and anatomical assessments as well as monitoring of adverse events. The primary endpoint is the change from baseline in visual acuity in the study eye, compared to control eye. Secondary study endpoints are, change from baseline in autofluorescence evaluation, microperimetry readings and other anatomic and functional outcomes (all in the study eye compared to control eye). Secondary endpoints also include safety assessments to be conducted throughout the study. The fellow eyes of these patients will be utilized as controls in this study and will receive no study treatment.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •18 Years and older
- •Able to give informed consent
- •Genetically confirmed diagnosis of choroideremia
- •Active disease visible clinically within the macula region
- •Best-corrected visual acuity equal to or worse than 20/32 but better than or equal to 20/200 in the study eye.
排除标准
- •Under the age of 18
- •History of amblyopia in the study eye
- •Men unwilling to use barrier contraception methods
- •Relevant grossly asymmetrical disease or other ocular morbidity which might confound use of the fellow eye as a long-term control
- •Any other significant ocular and non-ocular disease/disorder or retinal surgery
- •Contraindication to use of medications or contrast agents
- •Participated in research study involving an investigational product in the past 12 weeks
- •Having had gene or cellular therapy at any time prior to this study.
结局指标
主要结局
Change in Best Corrected Visual Acuity From Baseline
时间窗: Baseline, 24 Months
Patients will have an assessment of visual acuity using the Early Treatment of Diabetic Retinopathy Study (ETDRS) vision charts in both eyes. Low Luminance BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart and was reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). The study eye was defined as the eye that met inclusion/exclusion criteria with the worst standard BCVA. If the BCVA in both eyes was similar the Patient determines the worse eye be selected as the study eye. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
次要结局
- Change in Retinal Macular Autofluorescence From Baseline(12 and 24 months)
- Changes in Microperimetry From Baseline(Baseline to 24 months)
- Number of Participants Who Experience an Adverse Event(24 months)
研究者
Byron Lam
Professor of Ophthalmology
University of Miami