Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of NK: SEER-2

Study Overview
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Brief Summary
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The objective of this study is to compare the safety and efficacy of RGN-259 to placebo for the treatment of Neurotrophic Keratopathy (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.

Official Title
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A Phase 3, Multi-Center, Randomized, Parallel, Double Masked, Placebo-Controlled Clinical Study to Assess the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution for the Treatment of Neurotrophic Keratopathy (SEER-2)

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 written informed consent; Be able and willing to follow instructions, including participation in all study assessments and visits; At the time of Visit 1, have documentation or observation of a PED in one or both eyes, defined as a corneal epithelial defect that has not resolved after 1 week of conventional, nonsurgical treatment using non-preserved ocular lubricants, non-preserved topical ophthalmic antibiotics, oral doxycycline, patching, amniotic membrane, serum tears, and/or therapeutic contact lenses; Have stage 2 or 3 neurotrophic keratopathy (Mackie Classification) in at least one eye of which the longest dimension (length or width) of the defect measures a minimum length of 1 mm (study eye) and which is confirmed by the investigator not to be simply superficial punctate keratitis, at Visit 1; Have evidence of decreased corneal sensitivity ≤40 mm using the Cochet-Bonnet aesthesiometer at Visit 1; Have BCVA score ≤75 letter counts in the study eye based on the ETDRS chart; Have at least one eye (the same eye) satisfy all criteria for d, e, f, g above; Female subjects of child-bearing potential must be non-lactating and using and agree to continue using an acceptable method of contraception for at least 4 weeks prior to the first dose of study product and until 12 weeks after last dose, and have a negative urine pregnancy test during screening; Male subjects must agree to use an adequate method of contraception. Exclusion Criteria: Have any condition that, in the opinion of the Investigator, would interfere with the subject's ability to complete the study, would interfere with the interpretation of safety or efficacy, or would present an undue risk to the subject; Have any clinically significant slit-lamp findings in the study eye that in the opinion of the investigator may interfere with the study parameters; Clinically significant active blepharitis, meibomian gland dysfunction (MGD), or lid margin inflammation or active ocular allergy in study eye that requires treatment that in the opinion of the investigator may interfere with study parameters; Have a Unanesthetized Schirmer's test score of ≤3 mm at Visit 1; Have a lid function abnormality (ex. Lagophthalmos) which, in the opinion of the investigator, is the primary cause of the persistent epithelial defect; Have a previous fungal infection or be currently diagnosed with ongoing ocular infection or active inflammation in the study eye not related to NK; History of any ocular surgery (including laser or refractive surgical procedures) within the three months before study enrollment; Prior surgical procedure(s) for the treatment of NK (e.g. tarsorrhaphy, conjunctival flap, etc.) within the three months before study enrollment with the exception of amniotic membrane transplantation. Have any planned ocular surgical procedures or are likely to require ocular surgery for the study eye during the study; Have received Botox® injection to induce blepharoptosis in the study eye within 90 days prior to Visit 1; Have used contact lenses (for therapeutic or refractive correction) in the study eye within 14 days prior to Visit 1, or anticipate use of contact lenses during the study period; Have used Oxervate™ in the study eye within the past 2 months; Anticipate use of serum tears in the study eye during the study period; Have a presence or history of any ocular or systemic disorder or condition that might hinder the efficacy of the study treatment or its evaluation, could possibly interfere with the interpretation of study results, or could be judged by the Investigator to be incompatible with the study visit schedule or conduct; Have used drugs which affect lacrimation or function of the trigeminal nerve within 30 days of Visit 1 or anticipate use of these systemic medication throughout the course of the study; Have any autoimmune or chronic inflammatory disease that might have hindered the efficacy of the study treatment or its evaluation; Be on immunosuppressive therapy within 30 days prior to screening or is likely to require this during the course of the study; Have a known allergy and/or sensitivity to the study product or its components; Have a history of drug, medication or alcochol abuse or addiction; Have participated in an investigational drug study within 30 days prior to screening; Have fever, inflammation, or systemic signs of illness suggestive of systemic or invasive infection, including COVID-19 or a positive test for COVID-19, within 2 weeks prior to first dose of study drug.

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: 0.1% RGN-259 Opthalmic Solution<br>It is a preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into study eye(s), five times per day for 28 days | Drug: RGN-259<br>* A preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into study eye(s), five times per day for 28 days<br>* Other names: Timbetasin;|
| Placebo Comparator: Placebo Ophthalmic Solution (Vehicle for RGN-259 Ophthalmic Solution)<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. Direct instillation into study eye(s), five times per day for 28 days<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 of PED at Day 29 | Percentage of subjects achieving complete healing of the Persistent Epithelial Defect (PED) at Day 29 determined by corneal fluorescein staining as measured by the Central Reading Center. | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects achieving complete healing of PED at Day 29 | Percentage of subjects achieving complete healing of the PED determined by corneal fluorescein staining as measured by the Investigator. | Day 29 | 
| Percentage change from baseline of lesion size | Percentage change from baseline of lesion size determined by corneal fluorescein staining (measurements of greatest dimension of fluorescein staining) | Day 8, 15, 22, 29, 36, and 43 | 
| NK stage by Mackie classification | NK stage graded according to the Mackie classification (Stage I, II, III. Higher scores mean a better or worse outcome) | Day 8, 15, 22, 29, 36, and 43 | 
| Visual Acuity determined by ETDRS | Visual Acuity determined by Early Treatment of Diabetic Retinopathy Study (ETDRS) | Day 8, 15, 22, 29, 36, and 43 | 
| Corneal sensitivity inside the lesion determined by Cochet Bonnet aesthesiometer (Unit: mm) |  | Day 8, 15, 22, 29, 36, and 43 | 

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