NEXAGON for the Treatment of Corneal Persistent Epithelial Defects Following Severe Ocular Chemical and/or Thermal Injuries

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Randomized, Prospective, Double-masked, Vehicle-controlled Study to Assess the Efficacy and Safety of Nexagon® (NEXAGON) Applied Topically in Subjects With Corneal Persistent Epithelial Defects Resulting From Severe Ocular Chemical and/or Thermal Injuries

Conditions
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Corneal Persistent Epithelial Defect

Intervention / Treatment
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* Drug: Nexagon® (lufepirsen) High Dose Concentration
* Drug: Nexagon® (lufepirsen) Low Dose Concentration
* Drug: Vehicle
* Drug: Open-label Nexagon® (lufepirsen)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female of any age. 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. The PED is non-responsive to current standard of care for at least 14 days from injury. The PED measures at least 2 mm along the largest diameter at Day 1 of the Treatment Period. Providing written informed consent and ability to comply with the visit and dosing schedule. Exclusion Criteria: Subjects who will be unlikely to tolerate the wearing of a Bandage Contact Lens. Have active ocular infection. Subjects with corneal perforation or impending corneal perforation. 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. Subjects receiving systemic corticosteroids (equivalent to GREATER THAN 10 mg/day of prednisone) or immunosuppressive or chemotherapeutic agents unless the dose has remained unchanged for 30 days and will remain unchanged during the study. Subjects being treated with systemic corticosteroids (equivalent to >10 mg/day of prednisone) or immunosuppressive or chemotherapeutic agents unless the dose has remained unchanged for 30 days prior to Day 1. Subjects with severe lid abnormalities or ocular conditions that contribute to the persistence of the epithelial defect. Female subjects of childbearing potential who are pregnant, nursing, planning a pregnancy or not using an adequate and medically acceptable form of birth control. Subjects who have participated in an interventional clinical trial within 30 days prior to Day 1.
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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nexagon® (lufepirsen) High Dose Concentration<br> | Drug: Nexagon® (lufepirsen) High Dose Concentration<br>* Nexagon® (lufepirsen) is administered topically in the affected eye three (3) times over 28 days.<br>Drug: Open-label Nexagon® (lufepirsen)<br>* Open-label Nexagon® (lufepirsen) for participants who do not heal (re-epithelialize) at the end of the 28-day treatment phase.<br>|
| Experimental: Nexagon® (lufepirsen) Low Dose Concentration<br> | Drug: Nexagon® (lufepirsen) Low Dose Concentration<br>* Nexagon® (lufepirsen) is administered topically in the affected eye three (3) times over 28 days.<br>Drug: Open-label Nexagon® (lufepirsen)<br>* Open-label Nexagon® (lufepirsen) for participants who do not heal (re-epithelialize) at the end of the 28-day treatment phase.<br>|
| Placebo Comparator: Vehicle<br> | Drug: Vehicle<br>* Vehicle is administered topically in the affected eye three (3) times over 28 days.<br>* Other names: Placebo;Drug: Open-label Nexagon® (lufepirsen)<br>* Open-label Nexagon® (lufepirsen) for participants who do not heal (re-epithelialize) at the end of the 28-day treatment phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 56 days. | 
| 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. | Up to 30 days after last application of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to corneal epithelial recovery, as assessed by slit lamp examination. | The time (number of days) from randomization to the time of initial re-epithelialization for a cornea that remains re-epithelialized and durable for at least 28 days will be recorded following confirmation by slit lamp examination. | Within 28 days | 
| Improvement from baseline of visual acuity measured by the Snellen scale. | Improvement of visual acuity on the Snellen scale from baseline until study exit will be measured. | Up to 56 days | 
| The number of NEXAGON treatment doses required to achieve recovery of the corneal epithelium will be assessed. | The number of NEXAGON dose applications required to achieve corneal epithelial recovery will be recorded. Corneal epithelial recovery is defined as corneal reepithelialization and maintenance of a durable epithelium for at least 28 days and will be confirmed by slit lamp examination. | Within 56 days |