Corneal Endothelial Dystrophy, Fuchs Endothelial Corneal Dystrophy, Pseudophakic Bullous Keratopathy, Endothelial Dysfunction
Conditions
Brief summary
Prospective, multicenter, randomized, masked, vehicle-controlled, dose-escalation study
Detailed description
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.
Interventions
DRUGTTHX1114(NM141)
engineered FGF-1 delivered intracamerally
OTHERVehicle (placebo)
Placebo
Sponsors
Trefoil Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, Masked, Vehicle-controlled, Dose-escalation study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLTs/ Adverse Reactions | Day 90 | Suspected Adverse Reactions Reported Following Study Drug Adminsitration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vehicle (Placebo) Placebo weekly x 4
Vehicle (placebo): Placebo | 5 |
| Low Dose TTHX1114(NM141) low-dose weekly x 4
TTHX1114(NM141): engineered FGF-1 delivered intracamerally | 7 |
| Mid-dose TTHX1114(NM141) mid-dose weekly x 4
TTHX1114(NM141): engineered FGF-1 delivered intracamerally | 3 |
| High-dose TTHX1114(NM141) high-dose weekly x 4
TTHX1114(NM141): engineered FGF-1 delivered intracamerally | 7 |
| Total | 22 |
Baseline characteristics
| Characteristic | Vehicle (Placebo) | Low Dose | Mid-dose | High-dose | Total |
|---|---|---|---|---|---|
| Age, Continuous | 76.6 years STANDARD_DEVIATION 11.8 | 75.7 years STANDARD_DEVIATION 7.8 | 81.3 years STANDARD_DEVIATION 11 | 68.9 years STANDARD_DEVIATION 11.1 | 74.5 years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 3 Participants | 7 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 7 Participants | 3 Participants | 7 Participants | 22 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 2 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 7 | 0 / 3 | 0 / 7 |
| other Total, other adverse events | 2 / 5 | 1 / 7 | 2 / 3 | 3 / 7 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 | 0 / 3 | 0 / 7 |
Outcome results
Primary
DLTs/ Adverse Reactions
Suspected Adverse Reactions Reported Following Study Drug Adminsitration
Time frame: Day 90
Population: Safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vehicle (Placebo) | DLTs/ Adverse Reactions | 0 Participants |
| Low Dose | DLTs/ Adverse Reactions | 0 Participants |
| Mid-dose | DLTs/ Adverse Reactions | 0 Participants |
| High-dose | DLTs/ Adverse Reactions | 0 Participants |