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

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)

The objective of this study is to compare the safety and efficacy of RGN-259 to placebo for the treatment of Neurotrophic Keratopathy (NK)

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.

Inclusion Criteria

1. Be male or female of any race, at least 18 years of age;
2. Have provided written informed consent;
3. Be able and willing to follow instructions, including participation in all study assessments and visits;
4. At the time of Visit 1, have documentation or observation of a Persistent Epithelial Defect (PED) in one or both eyes, defined as a corneal epithelial defect that has not resolved after 1 week of conventional treatment using non-preserved ocular lubricants, non-preserved topical ophthalmic antibiotics, oral doxycycline, patching, amniotic membrane, serum tears, and/or therapeutic contact lenses;
5. 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;
6. Have evidence of decreased corneal sensitivity ≤40 mm using the Cochet-Bonnet aesthesiometer at Visit 1;
7. Have BCVA score ≤75 letter counts in the study eye based on the ETDRS protocol;
8. Have at least one eye (the same eye) satisfy all criteria for d, e, f, g above;
9. 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;
10. Male subjects must agree to use an adequate method of contraception.

Exclusion Criteria

1. 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.
2. Have any clinically significant slit-lamp findings in the study eye that in the opinion of the Investigator may interfere with the study parameters;
3. 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 the study parameters;
4. Have a Unanesthetized Schirmer's test score of ≤3 mm at Visit 1;
5. Have a lid function abnormality (ex. Lagophthalmos) which, in the opinion of the Investigator, is the primary cause of the persistent epithelial defect;
6. Have an ongoing ocular infection (bacterial, viral or fungal) or active inflammation (e.g., follicular conjunctivitis) in the study eye.
7. History of any ocular surgery (including laser or refractive surgical procedures) within the three months before study enrollment.
8. 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.
9. Have any planned ocular surgical procedures or are likely to require ocular surgery for the study eye during the study;
10. Have received Botox® injection to induce blepharoptosis in the study eye within 90 days prior to Visit 1;
11. 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.
12. Have used OxervateTM in the study eye within the past 2 months;
13. Anticipate use of serum tears in the study eye during the study period.
14. 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;
15. 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;
16. Have any autoimmune or chronic inflammatory disease that might have hindered the efficacy of the study treatment or its evaluation;
17. Be on topical (Ocular/Nasal) immunosuppressive therapy within 30 days prior to screening or is likely to require this during the course of the study;
18. Have a known allergy and/or sensitivity to the study product or its components;
19. History of drug, medication or alcohol abuse or addiction;
20. Have participated in an investigational drug study within 30 days prior to screening;
21. 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.