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
Trial Snapshot
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Incidence of DLTs
Study Overview
Brief Summary
The goal of this clinical trial is to evaluate the safety and efficacy of GEB-101 injection in subjects with TGFBI-related Corneal Dystrophy
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Masking Description
Phase 1, None (Open Label); Phase 2, double-blind masking.
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Phase 1
GEB-101 dose 1 GEB-101 dose 2 GEB-101 dose 3 GEB-101 dose 4 GEB-101 dose 5
Intervention: GEB-101 Injection (Genetic)
Phase 2
GEB-101(RP2D)
Intervention: GEB-101 Injection (Genetic)
Outcomes
Primary Outcomes
Incidence of DLTs
Time Frame: 30 Days
Number and proportion of dose limited toxicity（DLTs）
Incidence of AEs
Time Frame: 360 Days
Number and severity of overall and ocular and systemic adverse events (AEs)
Incidence of SAEs
Time Frame: 360 Days
Number and severity of overall and ocular and systemic serious adverse events (SAEs)
Secondary Outcomes
- 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)