Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Efficacy of EDIT-101 in Adult and Pediatric Participants With Leber Congenital Amaurosis Type 10 (LCA10), With Centrosomal Protein 290 (CEP290)-Related Retinal Degeneration Caused by a Compound Heterozygous or Homozygous Mutation Involving c.2991+1655A>G in Intron 26 (IVS26) of the CEP290 Gene ("LCA10-IVS26")
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 34
- 试验地点
- 5
- 主要终点
- Frequency of Adverse Events related to EDIT-101
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 EDIT-101 administered via subretinal injection in participants with LCA10 caused by a homozygous or compound heterozygous mutation involving c.2991+1655A>G in intron 26 of the CEP290 gene ("LCA10-IVS26").
详细描述
This is an open-label, single ascending dose study of EDIT-101 in adult and pediatric (ie, ages 3 to 17) participants with LCA10-IVS26. Up to 34 participants will be enrolled in up to 5 cohorts to evaluate up to 3 dose levels of EDIT-101 in this study. EDIT-101 is a novel gene editing product designed to eliminate the mutation on the CEP290 gene that results in the retinal degeneration that defines LCA10-IVS26.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female
- •At least 3 years of age at screening with CEP290-related retinal degeneration caused by a homozygous or compound heterozygous mutation involving c.2991+1655A>G in IVS26 of the CEP290 gene.
- •Visual Acuity:
- •Sentinel participant will have severe vision loss with a logMAR BCVA of ≥1.6 to 3.9 (20/800 or worse to LP) in the study eye
- •Non-sentinel participants must have BCVA between 1.0 - 3.0 logMAR in the study eye
排除标准
- •Other known disease-causing mutations
- •Achieves a passing score for the mobility course at the most difficult level
- •In either eye, active systemic or ocular/intraocular infection or inflammation
- •In either eye, history of steroid-responsive intraocular pressure with increases > 25 mm Hg following corticosteroid exposure
- •Any vaccination/immunization in the last 28 days before screening
- •Inability or unwillingness to take oral prednisone
- •Prior gene therapy or oligonucleotide treatment
研究组 & 干预措施
Adults Low Dose
Single dose of EDIT-101 administered by subretinal injection surgery
干预措施: EDIT-101 (Drug)
Adults Middle Dose
Single dose of EDIT-101 administered by subretinal injection surgery
干预措施: EDIT-101 (Drug)
Adults High Dose
Single dose of EDIT-101 administered by subretinal injection surgery
干预措施: EDIT-101 (Drug)
Pediatric Middle Dose
Single dose of EDIT-101 administered by subretinal injection surgery
干预措施: EDIT-101 (Drug)
Pediatric High Dose
Single dose of EDIT-101 administered by subretinal injection surgery
干预措施: EDIT-101 (Drug)
结局指标
主要结局
Frequency of Adverse Events related to EDIT-101
时间窗: 1 year
Number of participants experiencing procedural related adverse events
时间窗: 1 year
Incidence of dose limiting toxicities
时间窗: 1 year
次要结局
- Change from baseline in macula thickness(1 year)
- Change from baseline in pupillary response(1 year)
- Change from baseline in QOL score for Age >18 years if BCVA is worse than 1.0 logMAR in both eyes using the Impact of Vision Impairment for Very Low Vision(1 year)
- Change from baseline in Patient Global Impressions of Change score(1 year)
- Change from baseline in contrast sensitivity(1 year)
- Change from baseline in color vision score using the Farnsworth 15 score(1 year)
- Change from baseline in QOL score for Age <8 years using the Children's Visual Function Questionnaire(1 year)
- Change from baseline in visual field using kinetic perimetry(1 year)
- Change from baseline in LogMAR measurement of BCVA(1 year)
- Change from baseline in macular sensitivity as measured by microperimetry(1 year)
- Change from baseline in QOL score for Age 8 to <18 years using the Impact of Vision Impairment for Children(1 year)
- Maximum tolerated dose as determined by occurrence of dose limiting toxicities(1 year)
- Change from baseline in QOL score for Age >18 years if BCVA is 1.0 logMAR or better in both eyes using the Impact of Vision Impairment(1 year)
- Change from baseline in Mobility course score(1 year)
- Change from baseline in dark adapted visual sensitivity using Full field light sensitivity threshold (FST)(1 year)
- Change from baseline in gaze tracking(1 year)