A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease

Study Overview
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Brief Summary
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This is a Phase 2b, multicenter, vehicle-controlled, double-masked, randomized study. All subjects enrolled will have dry eye disease. The study consists of Screening and Baseline visits to determine eligibility followed by efficacy assessments at Day 14 (Visit 3), 28 (Visit 4) and 84 (Visit 5 / Study Exit). Safety will be assessed at all study visits. All subjects will be exposed to the Controlled Adverse Environment (CAE®) at the Screening, Baseline, Day 28 and Day 84 visits. Only subjects who qualify based on inclusion/exclusion criteria, will be enrolled in the study and randomized at a 1:1:1 ratio within each site, to receive AR-15512 0.0014%, AR-15512 0.003% or AR-15512 vehicle to be administered as 1 drop in each eye twice daily for 84 days.

Official Title
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A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease (COMET-1)

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: AR15512
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 30 years of age or older at the Screening visit Signs of DED at the Screening and Baseline visits assessed by corneal staining and Schirmer test Symptoms of DED at both Screening and Baseline visits assessed by SANDE questionnaire and ODS-VAS BCVA 20/200 (+0.70 LogMAR) or better in both eyes at both the Screening and Baseline visits Exclusion Criteria: History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or subject safety. Current evidence of other significant ophthalmic disease requiring topical medication (e.g. glaucoma, ocular hypertension), which may interfere with vision (e.g., cataract, macular degeneration) or other disease which the investigator believes may interfere with study findings or interpretation. History of ocular surgery within 1 year prior to the Screening visit. Corneal transplant in either or both eyes. Use of contact lenses in either eye within 7 days prior to the Screening visit or planned use during the study. Punctal or intracanalicular plug present in either eyelid within 1 year prior to the Screening visit or anticipated plug insertion or occlusion at any time during the study. Use of artificial tears within 2 hours prior to the Screening visit or anticipated use during the study. Regular use of any topical ocular medications (including use of ocular cyclosporine or other prescription ophthalmic solution for DED, topical ocular corticosteroid- or non-steroidal-anti-inflammatory agents, glaucoma medications or other over-the-counter, herbal, prescription, any topical antibiotics, topical antihistamines, mast stabilizers, or nutritional supplements with the exception of artificial tears), within 30 days prior to the Screening visit or anticipated use during the study. Note: Occasional (as needed) >24 hours prior to the Screening Visit may be permitted Use of medications associated with the treatment of severe DED and/or Meibomian gland disease such as oral pilocarpine, oral cevimeline, oral macrolides, oral tetracyclines, oral tetracycline derivatives, and oral retinoids within 90 days prior to the Baseline visit or anticipated use during the study Use of systemic corticosteroids started < 90 days prior to the Baseline Visit or a change in dosage is anticipated during the study. Note: Non-ocular topically applied corticosteroids (including nasal sprays and inhalers) will be permitted during the study and the dose is not required to be stable. Use of TrueTear® within 45 days of the Screening visit or anticipated use during the study. Use of lid heating therapy or Meibomian gland probing/therapeutic expression within 1 year prior to the Screening visit or anticipated during the study. Use of systemic immunomodulators started < 90 days prior to the Baseline visit or a change in dosage is anticipated during the study. Any systemic medication known to cause ocular drying (ex/antihistamines, anti-depressants, beta-blockers) started < 14 days prior to the Screening visit or a change in dosage is anticipated during the study. Note: Occasional (as needed) use of medications such as systemic antihistamines will be permitted Diagnosis of recurrent, ongoing, or active ocular infection including, but not limited to herpes simplex or zoster, vaccinia, varicella, tuberculosis of the eye, acanthamoeba, or fungal disease. History or presence of significant systemic disease.

Ages Eligible for Study
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Minimum Age: 30 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
Interventional Model Description: Subjects will be randomized at a 1:1:1 ratio within each site to receive AR-15512 0.0014%, AR-15512 0.003% or AR 15512 vehicle
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AR15512 Ophthalmic Solution (0.0014%)<br>Low Dose | Drug: AR15512<br>* Administered via topical ocular instillation, one drop per eye, twice daily for 84 days. Both eyes will be treated.<br>|
| Experimental: AR15512 Ophthalmic Solution (0.003%)<br>High Dose | Drug: AR15512<br>* Administered via topical ocular instillation, one drop per eye, twice daily for 84 days. Both eyes will be treated.<br>|
| Placebo Comparator: Vehicle<br>AR15512 Ophthalmic Solution Vehicle | Drug: Vehicle<br>* Administered via topical ocular instillation, one drop per eye, twice daily for 84 days. Both eyes will be treated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Discomfort Score (ODS) on a Visual Analogue Scale (VAS) from 0 (no ocular discomfort) to 100 (maximum ocular discomfort) millimeters | Improvement from baseline in pre-Controlled Adverse Environment (CAE) ODS-VAS where a lower score is indicative of a better outcome. | 28 days | 
| Anesthetized Schirmer Test from 0 to 35 millimeters | Improvement from baseline in pre-Controlled Adverse Environment (CAE) anesthetized Schirmer score where a higher score is indicative of a better outcome. | 28 days |