A Phase 1/ Phase 2 Study of TTHX1114(NM141)

Study Overview
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Brief Summary
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Prospective, multicenter, randomized, masked, vehicle-controlled, dose-escalation study

Detailed Description
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This is a prospective, multi-center, randomized, masked, vehicle-controlled, dose-escalation study that will include an observational (no intervention) sub-study. Eligible subjects with moderate to severe corneal endothelial dystrophy (defined as Endothelial Cell Density < 2000 mm^2) in at least one eye will be enrolled and randomized.

Official Title
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A Phase 1/ Phase 2 Study Evaluating the Safety and Efficacy of the Investigational New Drug TTHX1114(NM141) on the Regeneration of Corneal Endothelial Cells in Patients With Corneal Endothelial Dystrophies Following Intracameral Delivery

Conditions
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Corneal Endothelial Dystrophy, Fuchs Endothelial Corneal Dystrophy, Pseudophakic Bullous Keratopathy, Endothelial Dysfunction

Intervention / Treatment
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* Drug: TTHX1114(NM141)
* Other: Vehicle (placebo)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Fuchs Endothelial Corneal Dystrophy, pseudophakic bullous keratopathy, or endothelial dysfunction/ insufficiency due to surgical intervention diagnosed more than 6 months prior to Study Day 0 Central endothelial cell count of < 2000 mm^2 in at least one eye as determined by the central reading facility Key Exclusion Criteria: Conditions that would impair examination of the anterior chamber structure Documented repeated elevated intra ocular pressure (in either eye) Corneal transplant (in either eye) Posterior Polymorphous Corneal Dystrophy (PPCD) History of uveitis or herpetic keratitis Cataract surgery within the past 3 months Refractive surgery (in the Study Eye) Anterior Chamber IOL placement (in the Study Eye) Active extra-ocular inflammation from any non-infectious or infectious cause within the past 6 months Expected or planned ocular surgery within the next 3 months Use of cytotoxic chemotherapy within the last 1 month Treatment with a rho kinase inhibitor within the last 3 months Use of cyclosporine ophthalmic emulsion or lifitegrast ophthalmic solution in the last 30 days Systemic or ophthalmic corticosteroid use in the 30 days prior to Study Day 0 unless approved by the Medical Monitor History of significant allergy, hypersensitivity, or intolerance to any drug compound, food, or other substance Unwilling to use birth control

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Masked, Vehicle-controlled, Dose-escalation study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle (placebo)<br>Placebo weekly x 4 | Other: Vehicle (placebo)<br>* Placebo<br>|
| Experimental: Low dose<br>TTHX1114(NM141) low-dose weekly x 4 | Drug: TTHX1114(NM141)<br>* engineered FGF-1 delivered intracamerally<br>|
| Experimental: Mid-dose<br>TTHX1114(NM141) mid-dose weekly x 4 | Drug: TTHX1114(NM141)<br>* engineered FGF-1 delivered intracamerally<br>|
| Experimental: High-dose<br>TTHX1114(NM141) high-dose weekly x 4 | Drug: TTHX1114(NM141)<br>* engineered FGF-1 delivered intracamerally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLTs/ Adverse Reactions | Suspected Adverse Reactions Reported Following Study Drug Adminsitration | Day 90 |