Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy : SEER-1

Study Overview
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Brief Summary
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The objective of this study is to assess the safety and efficacy of RGN-259 Ophthalmic Solution compared to placebo for the treatment of NK.

Detailed Description
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Neurotrophic keratopathy (NK) is a degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervation. The resulting loss of corneal sensitivity (anesthesia) leads to a reduction in lacrimation and a decline in status, metabolism, and mitosis of corneal epithelial cells. Previous studies (physician-sponsored studies) used to treat to nine patients with NK, six of whom had discrete geographic, non-healing lesions, and three of whom had punctate lesions and the study result reported.

Official Title
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Phase 3, Multi-Center, Randomized, Double Masked, Placebo Controlled Clinical Study to Assess the Safety and Efficacy of RGN-259 Ophthalmic Solution for the Treatment of Neurotrophic Keratopathy: SEER-1

Conditions
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Neurotrophic Keratopathy

Intervention / Treatment
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* Drug: RGN-259
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be male or female of any race, at least 18 years of age Have provided verbal and written informed consent. Be able and willing to follow instructions, including participation in all study assessments and visits; Have stage 2 or 3 neurotrophic keratopathy in at least one eye If a female of childbearing potential, have a negative urine pregnancy test at Visit 1 and agree to use an adequate method of birth control throughout the study period. Exclusion Criteria: Have any clinically significant slit lamp findings at Visit 1 that in the opinion of the investigator may interfere with the study parameters; Have significant blepharitis, meibomian gland dysfunction (MGD), lid margin inflammation or active ocular allergy that requires treatment Have a lid function abnormality (ex. Lagophthalmos) which, in the opinion of the investigator, is the primary cause of the persistent epithelial defect; Be diagnosed with ongoing ocular infection (bacterial, viral or fungal) or active inflammation (e.g. follicular conjunctivitis) not related to NK Anticipate the use of fluoroquinolone-containing antibiotic eye drops during the study; Have used contact lenses (excluding therapeutic contact lenses) within 14 days prior to Visit 1 or anticipates use of contact lenses during the study period; Have an uncontrolled systemic disease that in the opinion of the investigator may interfere with the study parameters; Anticipate a change in immunosuppressive therapy during the course of the study;

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RGN-259<br>It is a preservative-free, sterile eye drop solution containing Tβ4 | Drug: RGN-259<br>* A preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into affected eye(s), five times a day for 4 weeks.<br>* Other names: Tβ4;|
| Placebo Comparator: Placebo<br>It is composed of the same excipients as RGN-259 but does not contain Tβ4. | Drug: Placebo<br>* It is composed of the same excipients as RGN-259 but does not contain Tβ4<br>* Other names: Vehicle Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Complete Healing at Day 29. | Percentage of subjects achieving complete healing of the persistent epithelial defect as determined by corneal fluorescein staining at day 29 after first dosing. | 29 days after first dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving Complete Healing at 8, 15, 22, 36, 43 Days | Percentage of subjects achieving complete healing of the Persistent Epithelial Defect(PED) determined by corneal fluorescein staining at 8, 15, 22, 36, 43 days after first dosing. | 8, 15, 22, 36, 43 days after first dosing | 
| Epithelial Defect Measurement and Classification as Stage 1, 2 or 3 Using Mackie Classification. | Epithelial Defect Measurement and Classification as stage 1, 2 or 3 using Mackie Classification at 8, 15, 22, 29, 36, 43 days after first dosing | 8, 15, 22, 29, 36, 43 days after first dosing | 
| Tear Film Break-up Time at 29, 36, 43 Days | Tear Film Break-up Time at 29, 36, 43 days after first dosing | 29, 36, 43 days after first dosing | 
| Ocular Discomfort by Questionnaire at 8, 15, 22, 29, 36, 43 Days After First Dosing | Ocular Discomfort by Questionnaire at 8, 15, 22, 29, 36, 43 Days After First Dosing at Visits 2, 3, 4, 5, 6, and 7 (The scale used to determine the difference in Ocular Discomfort by questionnaire on each visit is from 0(None) to 5(Most). This outcome was calculated from two time points as the value at the later time point minus the value at the first dosing points and the lower value are considered to be a better outcome. and the all relevant time points used in the calculation in the Time Frame was 8, 15, 22, 29, 36, 43 days.) | 8, 15, 22, 29, 36, 43 days after first dosing | 
| Visual Acuity(logMAR) at 8, 15, 22, 29, 36, 43 Days | Visual acuity(logMAR) at 8, 15, 22, 29, 36, 43 days (The Visual acuity was assessed by LogMAR calculation method. In the case of the LogMAR method, Each letter has a score value of 0.02 log units. Since there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units. and The lower value are considered to be a better outcome.) The formula used in calculating the score is: LogMAR VA = 0.1 + LogMAR value of the best line read - 0.02 X (number of optotypes read) used to determine the difference in Ocular Discomfort by questionnaire on each visit is the ORA scale: 0 None to 5: Most And as this outcome was calculated from two time points as the value at the later time point minus the value at the first dosing points, The lower value are considered to be a better outcome. and the all relevant time points used in the calculation in the Time Frame was 8, 15, 22, 29, 36, 43 days.) | 8, 15, 22, 29, 36, 43 days after first dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurotrophic Keratopathy, NK