Safety and Efficacy Study of GEB-101 Injection in Subjects With TGFBI-related Corneal Dystrophy

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.

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.