A Multicenter, Phase I/II, Clinical Study to Evaluate the Safety, Tolerability and Efficacy of Intrastromal Injection of Genome-editing GEB-101 in Participants With TGFBI-related Corneal Dystrophy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Incidence of DLTs
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and efficacy of GEB-101 injection in subjects with TGFBI-related Corneal Dystrophy
详细描述
This is a Phase 1/2 seamless, adaptive, multi-center, sequential study evaluates the safety and efficacy of GEB-101 in adult participants with TGFBI-related corneal dystrophy.
The Phase 1 part is a single-arm, open-label, dose-escalation study with three planned cohorts , followed by 2 expansion cohorts at the recommended Phase 2 dose.
The Phase 2 transitions to a randomized, double-blind, vehicle-controlled, self-controlled design.
After completing the primary 1-year follow-up, a long-term follow-up will be proposed to all the participants who received GEB-101 treatment, with close in site follow-up conducted from Year 2 to Year 5, followed by telephone or questionnaire-based follow-up until Year 15.
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
盲法说明
Phase 1, None (Open Label); Phase 2, double-blind masking.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, age 18-70 years (inclusive).
- •TGFBI gene mutation confirmed.
- •Patients with corneal dystrophy who are symptomatic.
- •Willing and able to give signed informed consent and follow study instructions.
排除标准
- •In either eye: Have any active infection, glaucoma, corneal disease, or other ocular conditions that may affect the assessment of efficacy or safety.
- •In the study eye: Have a history of specific intraocular or corneal surgery, or the presence of active intraocular inflammation or vitreous hemorrhage.
- •Patient with other corneal disorders that may hinder therapeutic surgery or interfere with the interpretation of study results.
- •Prior gene therapy administration in either eye.
- •Active infection occurring or suspected within 4 weeks prior to the investigational product, requiring systemic anti-infective therapy.
- •Subjects with a history of major cardiovascular events within 6 months, the presence of any clinically significant condition, a diagnosis of malignancy within 5 years (with specified exceptions), or active infection with HIV, syphilis, hepatitis C, or hepatitis B.
- •Female subjects who are pregnant, breastfeeding, or planning to become pregnant during the study period.
- •Disease, condition, or disorder that in the judgement of Investigator could confound study assessments or limit compliance to study protocol.
研究组 & 干预措施
Phase 1
GEB-101 dose 1 GEB-101 dose 2 GEB-101 dose 3 GEB-101 dose 4 GEB-101 dose 5
干预措施: GEB-101 Injection (Genetic)
Phase 2
GEB-101(RP2D)
干预措施: GEB-101 Injection (Genetic)
结局指标
主要结局
Incidence of DLTs
时间窗: 30 Days
Number and proportion of dose limited toxicity（DLTs）
Incidence of AEs
时间窗: 360 Days
Number and severity of overall and ocular and systemic adverse events (AEs)
Incidence of SAEs
时间窗: 360 Days
Number and severity of overall and ocular and systemic serious adverse events (SAEs)
次要结局
- Change in BCVA from baseline over time(360 Days)
- Change in corneal haze level from baseline over time(360 Days)
- Time to recurrence of disease(360 Days)