Corneal Persistent Epithelial Defect
Conditions
Brief summary
This study will enroll participants with a non-infected, corneal persistent epithelial defect (PED) resulting from an ocular chemical and/or thermal ocular injury which is non-responsive or refractory to current standard of care for at least 14 days. It will assess the efficacy and safety of Nexagon® (lufepirsen) plus standard of care versus NEXAGON-vehicle (placebo) plus standard of care. The recovery of the corneal epithelium will be the primary outcome measure, defined as a cornea that re-epithelializes by Day 28 of treatment and remains re-epithelialized for at least a further 28 days.
Interventions
DRUGNexagon® (lufepirsen) High Dose Concentration
Nexagon® (lufepirsen) is administered topically in the affected eye three (3) times over 28 days.
DRUGNexagon® (lufepirsen) Low Dose Concentration
Nexagon® (lufepirsen) is administered topically in the affected eye three (3) times over 28 days.
DRUGVehicle
Vehicle is administered topically in the affected eye three (3) times over 28 days.
DRUGOpen-label Nexagon® (lufepirsen)
Open-label Nexagon® (lufepirsen) for participants who do not heal (re-epithelialize) at the end of the 28-day treatment phase.
Sponsors
Amber Ophthalmics, Inc.
Glaukos Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Male and female of any age. 2. The presence of a non-infected, corneal persistent epithelial defect (PED) which has resulted from a severe chemical and/or thermal (burn) injury to one or both eyes. 3. The PED is non-responsive to current standard of care for at least 14 days from injury. 4. The PED measures at least 2 mm along the largest diameter at Day 1 of the Treatment Period. 5. Providing written informed consent and ability to comply with the visit and dosing schedule.
Exclusion criteria
1. Have active ocular infection. 2. Subjects with corneal perforation or impending corneal perforation. 3. Subjects with any other past or present ophthalmic disease or medical condition that, in the Investigator's opinion, may affect the safety of the subject or the outcome of the study. 4. Subjects with severe lid abnormalities or ocular conditions that contribute to the persistence of the epithelial defect. 5. Female subjects of childbearing potential who are pregnant, nursing, planning a pregnancy or not using an adequate and medically acceptable form of birth control. 6. Subjects who have participated in an interventional clinical trial within 30 days prior to Day 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Proportion of Subjects Achieving Corneal Epithelial Recovery, as Assessed by Slit Lamp Examination. | Up to 56 days. | Corneal epithelial recovery, defined as corneal reepithelialization and maintenance of a durable epithelium for at least 28 days, will be assessed by slit lamp examination. |
| Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v 5.0 | Up to 30 days after last application of intervention | Incidence of Treatment Emergent Adverse Events as assessed by CTCAE v 5.0. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nexagon® (Lufepirsen) High Dose Concentration Nexagon® (lufepirsen) High Dose Concentration: Nexagon® (lufepirsen) is administered topically in the affected eye three (3) times over 28 days.
Open-label Nexagon® (lufepirsen): Open-label Nexagon® (lufepirsen) for participants who do not heal (re-epithelialize) at the end of the 28-day treatment phase. | 12 |
| Nexagon® (Lufepirsen) Low Dose Concentration Nexagon® (lufepirsen) Low Dose Concentration: Nexagon® (lufepirsen) is administered topically in the affected eye three (3) times over 28 days.
Open-label Nexagon® (lufepirsen): Open-label Nexagon® (lufepirsen) for participants who do not heal (re-epithelialize) at the end of the 28-day treatment phase. | 12 |
| Vehicle Vehicle: Vehicle is administered topically in the affected eye three (3) times over 28 days.
Open-label Nexagon® (lufepirsen): Open-label Nexagon® (lufepirsen) for participants who do not heal (re-epithelialize) at the end of the 28-day treatment phase. | 11 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Nexagon® (Lufepirsen) High Dose Concentration | Nexagon® (Lufepirsen) Low Dose Concentration | Vehicle | Total |
|---|---|---|---|---|
| Age, Continuous | 25.9 years STANDARD_DEVIATION 20.42 | 30.3 years STANDARD_DEVIATION 16.38 | 30.9 years STANDARD_DEVIATION 19.03 | 29.0 years STANDARD_DEVIATION 18.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 12 Participants | 11 Participants | 34 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 11 Participants | 11 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment India | 11 participants | 11 participants | 11 participants | 33 participants |
| Region of Enrollment United States | 1 participants | 1 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 8 Participants | 28 Participants |
| Subjects with of Persistent Epithelial Defect | 12 Participants | 12 Participants | 11 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 7 / 12 | 8 / 12 | 7 / 11 |
| serious Total, serious adverse events | 0 / 12 | 1 / 12 | 0 / 11 |
Outcome results
Primary
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v 5.0
Incidence of Treatment Emergent Adverse Events as assessed by CTCAE v 5.0.
Time frame: Up to 30 days after last application of intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nexagon® (Lufepirsen) High Dose Concentration | Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v 5.0 | 7 Participants |
| Nexagon® (Lufepirsen) Low Dose Concentration | Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v 5.0 | 8 Participants |
| Vehicle | Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v 5.0 | 7 Participants |
Primary
The Proportion of Subjects Achieving Corneal Epithelial Recovery, as Assessed by Slit Lamp Examination.
Corneal epithelial recovery, defined as corneal reepithelialization and maintenance of a durable epithelium for at least 28 days, will be assessed by slit lamp examination.
Time frame: Up to 56 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nexagon® (Lufepirsen) High Dose Concentration | The Proportion of Subjects Achieving Corneal Epithelial Recovery, as Assessed by Slit Lamp Examination. | 8 Participants |
| Nexagon® (Lufepirsen) Low Dose Concentration | The Proportion of Subjects Achieving Corneal Epithelial Recovery, as Assessed by Slit Lamp Examination. | 8 Participants |
| Vehicle | The Proportion of Subjects Achieving Corneal Epithelial Recovery, as Assessed by Slit Lamp Examination. | 3 Participants |