Corneal Abnormality, Corneal Dystrophies, Corneal Dystrophies, Hereditary, Hereditary Corneal Dystrophy
Conditions
Keywords
Corneal Dystrophies, Corneal Dystrophy, TGFBI Corneal Dystrophies, Granular Corneal Dystrophy, Lattice Corneal Dystrophy, Reis-Bücklers Corneal Dystrophy, Thiel-Behnke Corneal Dystrophy, TGFBI-related corneal dystrophies, Gene Therapy
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.
Interventions
GENETICGEB-101 Injection
Single intrastromal injection
Sponsors
GenEditBio Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Phase 1, None (Open Label); Phase 2, double-blind masking.
Intervention model description
Phase 1, single group assignment; Phase 2, parallel assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of DLTs | 30 Days | Number and proportion of dose limited toxicity（DLTs） |
| Incidence of AEs | 360 Days | Number and severity of overall and ocular and systemic adverse events (AEs) |
| Incidence of SAEs | 360 Days | Number and severity of overall and ocular and systemic serious adverse events (SAEs) |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Countries
China, United States
Outcome results
None listed