Study Evaluating the Safety and Efficacy of AR-15512 (COMET-3)

• ClinicalTrials.gov Identifier: NCT05360966
• Recruitment Status: Recruiting
• First Posted: May 4, 2022
• Last Update Posted: January 19, 2023
• Sponsor: Aerie Pharmaceuticals
• Information provided by (Responsible Party): Aerie Pharmaceuticals

Study Description

Brief Summary:

This will be a Phase 3, multicenter, vehicle-controlled, double-masked, randomized study conducted at approximately 20 sites in the United States. All subjects enrolled will have dry eye disease (DED). The study will consist of Screening (Day -14) and Baseline (Day 1) visits as well as visits at Day 7, Day 14, Day 28, and Day 90 (Study Exit).

Condition or disease	Intervention/treatment	Phase
Dry Eye Disease	Drug: AR-15512 Ophthalmic Solution; Drug: Vehicle	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 460 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Qualified subjects will be enrolled in the study and randomized in a 1:1 ratio within each site to receive 0.003% AR 15512 or AR-15512 vehicle to be administered twice daily (BID) as 1 drop in each eye for 90 days.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: During the randomized treatment period, the investigator and site staff performing eligibility / efficacy and safety assessments and the subjects will be masked.
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study Evaluating the Safety and Efficacy of AR-15512, a Cold Thermoreceptor Modulator, for the Treatment of Dry Eye Disease (COMET-3)
• Actual Study Start Date: July 18, 2022
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: AR-15512 Ophthalmic Solution (0.003%); 0.003% AR-15512 to be administered BID for 90 days. Both eyes will be treated.	Drug: AR-15512 Ophthalmic Solution; Topical ocular administration of one drop in both eyes BID for 90 days.
Placebo Comparator: Vehicle; AR-15512 vehicle to be administered BID for 90 days. Both eyes will be treated.	Drug: Vehicle; Topical ocular administration of one drop in both eyes BID for 90 days.

Outcome Measures

Primary Outcome Measures :

1. Unanesthetized Schirmer test [ Time Frame: Day 14 ]

   Proportion of subjects ≥ 10 mm increase in unanesthetized Schirmer score.

   Schirmer strips placed, without anesthesia, in both eyes measure the amount of tear wetting over a 5-minute period, in whole millimeters to a maximum score of 35 mm. An ≥ 10 mm score over time indicates a better outcome.

Secondary Outcome Measures :

1. SANDE (Symptom Assessment iN Dry Eye) Questionnaire Score [ Time Frame: Day 28 ]

   Change from Baseline in SANDE score.

   The SANDE questionnaire consists of two visual analogue scales (VAS), each ranging from 0mm to 100mm to indicate the frequency (from "Rarely" to "All the Time") and severity (from "Very Mild" to "Very Severe") of dry eye symptoms. A higher score indicates greater frequency or severity. Each subject marks both VAS to indicate their level of frequency and severity. The SANDE score is calculated by multiplying the frequency score by the severity score and obtaining the square root. A reduced SANDE score over time indicates a better outcome.

2. SANDE (Symptom Assessment iN Dry Eye) Questionnaire Score [ Time Frame: Day 7, 14, 90 ]

   Change from Baseline in SANDE score.

   The SANDE questionnaire consists of two visual analogue scales (VAS), each ranging from 0mm to 100mm to indicate the frequency (from "Rarely" to "All the Time") and severity (from "Very Mild" to "Very Severe") of dry eye symptoms. A higher score indicates greater frequency or severity. Each subject marks both VAS to indicate their level of frequency and severity. The SANDE score is calculated by multiplying the frequency score by the severity score and obtaining the square root. A reduced SANDE score over time indicates a better outcome.

3. Unanesthetized Schirmer score [ Time Frame: Day 7, 14, 28 & 90 ]

   Change from Baseline

   Schirmer strips placed, without anesthesia, in both eyes measure the amount of tear wetting over a 5-minute period, in whole millimeters to a maximum score of 35 mm. An increased score over time indicates a better outcome.

4. Ocular Discomfort Score (ODS) - VAS [ Time Frame: Day 28 & 90 ]

   Change from Baseline

   Subjects mark a visual analogue scale (VAS) between 0mm to 100mm to indicate (from "no symptom" to "maximal symptom") their ocular discomfort. A reduced score over time indicates a better outcome.

5. Eye Dryness Score (EDS) - VAS [ Time Frame: Day 28 & 90 ]

   Change from Baseline

   Subjects mark a visual analogue scale (VAS) between 0mm to 100mm to indicate (from "no symptom" to "maximal symptom") their eye dryness. A reduced score over time indicates a better outcome.

6. Unanesthetized Schirmer score [ Time Frame: Day 7, 28 & 90 ]

   Proportion of subjects with ≥ 10 mm increase in score

   Schirmer strips placed, without anesthesia, in both eyes measure the amount of tear wetting over a 5-minute period, in whole millimeters to a maximum score of 35 mm. An ≥ 10 mm score over time indicates a better outcome.

7. Quality of Life VAS [ Time Frame: Day 7, 14, 28 & 90 ]

   Change from Baseline

   Subjects mark a visual analogue scale (VAS) between 0mm to 100mm to indicate (from "strongly disagree" to "strongly agree") their agreement with the statement "Over the past 3 days my dry eye has interfered with my daily activities and reduced my quality of life". A reduced score over time indicates a better outcome.

8. Ocular Pain - VAS [ Time Frame: Day 90 ]

   Change from Baseline

   Subjects mark a visual analogue scale (VAS) between 0mm to 100mm to indicate (from "no symptom" to "maximal symptom") their ocular discomfort. A reduced score over time indicates a better outcome.

9. Conjunctival Redness [ Time Frame: Day 90 ]

   Change from Baseline

   Investigators or designated sub-Investigators grade redness of the eye on a scale from 0 to 4 (from 0 "normal" to 4 "severe"). A reduced score over time indicates a better outcome.

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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
• Corrected visual acuity (+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
• Regular use of lid hygiene within 14 days prior to the Screening visit or any planned use during the study
• Use of artificial tears within 2 hours prior to the Screening visit or anticipated use during the study
• Use of any topical ocular anti-inflammatory medication within 30 days prior to the Screening visit or anticipated use during the study (e.g., ocular cyclosporine [Restasis®, Cequa™], lifitegrast [Xiidra®], or any other prescription ophthalmic product for DED, topical ocular corticosteroid- or non-steroidal-anti-inflammatory agents
• Use of Tyrvaya™ (varenicline solution, nasal spray 0.03mg) within 30 days prior to the Screening visit or anticipated use during the study
• Use of medications for 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 30 days prior to the Screening visit or anticipated use during the study.
• Initiation, discontinuation, or change in dose of a systemic medication known to cause ocular drying (e.g., antihistamines or tricyclic antidepressants) less than 14 days prior to the Screening visit or a change in dosage is anticipated during the study.
• Initiation, discontinuation, or change in dose of a systemic corticosteroid less than 60 days prior to the Screening visit or a change in dosage is anticipated during the study.
• Initiation, discontinuation, or change in dose of a systemic immunomodulator (e.g., hydroxychloroquine, methotrexate, cyclosporine) less than 60 days prior to the Screening visit or a change in dosage is anticipated during the study
• History or presence of significant systemic disease (i.e.: cardiovascular, pulmonary, hepatic, renal, hematologic, immunologic)

Contacts and Locations

Contacts

Contact: Antoinette Brown; 949-526-8708; COMET-3@aeriepharma.com

Contact: Raul Ramos; 908-440-0086; COMET-3@aeriepharma.com

Locations

United States, California

Eye Research Foundation; Recruiting

Newport Beach, California, United States, 92663

United States, Florida

Argus Research Center; Not yet recruiting

Cape Coral, Florida, United States, 33904

United States, Illinois

Jacksoneye, S.C.; Not yet recruiting

Lake Villa, Illinois, United States, 60046

United States, Indiana

Pankratz Eye Institute; Recruiting

Columbus, Indiana, United States, 47203

United States, Massachusetts

Andover Eye Associates - Andover; Recruiting

Andover, Massachusetts, United States, 01810

Andover Eye Associates - Raynham; Recruiting

Raynham, Massachusetts, United States, 02767

United States, North Carolina

Wilmington Eye; Not yet recruiting

Leland, North Carolina, United States, 28451

Pure Ophthalmic Research; Recruiting

Mint Hill, North Carolina, United States, 28227

United States, Rhode Island

Andover Eye Associates; Recruiting

Warwick, Rhode Island, United States, 02886

United States, Virginia

Piedmont Eye Center; Not yet recruiting

Lynchburg, Virginia, United States, 24502

Virginia Eye Institute; Recruiting

Richmond, Virginia, United States, 23230

Sponsors and Collaborators

Aerie Pharmaceuticals

Investigators

• Study Director: Michelle Senchyna, PhD; Aerie Pharmaceuticals

More Information

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05360966
• Other Study ID Numbers: AR-15512-CS302
• First Posted: May 4, 2022
• Last Update Posted: January 19, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Ophthalmic Solutions; Pharmaceutical Solutions