THOR - Tübingen Choroideremia Gene Therapy Trial Open Label Phase 2 Clinical Trial 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
- best corrected visual acuity in treated eye
研究概览
简要总结
An open label monocentric phase II trial in adult males with a clinical phenotype of choroideremia and a confirmed molecular diagnosis of a null mutation in the gene encoding REP1 to assess the anatomical and functional outcomes, as well as the safety of a single subretinal injection of rAAV2.REP1 in 6 subjects with genetically confirmed choroideremia for up to 24 months.
详细描述
Study name: THOR - Tübingen Choroideremia gene therapy trial open label Phase 2 clinical trial using an adeno-associated viral vector (AAV2) encoding Rab-escort protein 1 (REP1)
Phase: Phase II
Indication: Adult males with a clinical phenotype of choroideremia and a confirmed molecular diagnosis of a null mutation in the gene encoding REP1
Aim of study: To assess the anatomical and functional outcomes, as well as the safety of a single subretinal injection of rAAV2.REP1 in subjects with genetically confirmed choroideremia for up to 24 months.
Primary Endpoint: Change from baseline in best corrected visual acuity in treated eye, compared to untreated control eye
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
- •Participant is willing and able to give informed consent for participation in the study.
- •Male aged 18 years or above.
- •Genetically confirmed diagnosis of choroideremia. Patients without a confirmed mutation in the CHM gene, but who have the clinical phenotype typical of choroideremia can only be enrolled if they meet all the following three criteria: (i) family history consistent with X-linked inheritance, (ii) absent REP1 protein on Western blot of a blood sample and, (iii) normal RPE65 gene on sequencing.
- •Active disease visible clinically within the macula region
- •Best-corrected visual acuity equal to or worse than 6/9 (20/32; Decimal 0.63; LogMAR 0.2) but better than or equal to 6/60 (20/200; Decimal 0.1; LogMAR 1.0) in the study eye.
排除标准
- •Female and child participants (under the age of 18)
- •Participants with a history of amblyopia in the study eye
- •Men unwilling to use barrier contraception methods, if relevant
- •Absence of quantifiable visual function in the fellow eye 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 which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study, or the participant's ability to participate in the study. This would include not taking or having a contraindication to oral prednisolone, such as a history of gastric ulcer or significant side effects.
- •Participants who have participated in another research study involving an investigational product in the past 12 weeks, or having had gene or cellular therapy at any time prior to this study.
- •Patients with amblyopic eyes should be excluded in general, since the evaluation of the primary endpoint presupposes the ability to fixate both eyes
- •Prior intraocular surgery within six months
- •Intolerance to local anesthesia and/or contraindication to IVT surgery (anemia Hb<8g/dl, severe cardiovascular disease, severe coagulopathy, etc.)
- •High fever or high fever disease, patients with a history of autoimmune conditions/ other systemic diseases that may have ocular manifestations (e.g. sarcoidosis) or neurodegenerative conditions (e.g. multiple sclerosis, neuromyelitis optica, Parkinson's disease)
- •Patients suffering from other genetic mutations leading to pathological retinal conditions
- •Patients treated by oral corticoids within 14 days prior inclusion at the study entry
结局指标
主要结局
best corrected visual acuity in treated eye
时间窗: up to 24 months after vector administration
Change from baseline in best corrected visual acuity in treated eye, compared to untreated control eye up to 24 months after vector administration
次要结局
- fundus autofluorescence analysis(24 months after vector administration)
- colour vision(24 months after vector administration)
- Absence of vector-related adverse reactions(24 months after vector administration)
- contrast sensitivity(24 months after vector administration)
- central visual field using microperimetry readings(24 months after vector administration)