Study Evaluating the Safety and Efficacy of AR-15512 (COMET-2)

A Phase 3 Study Evaluating the Safety and Efficacy of AR-15512, a Cold Thermoreceptor Modulator, for the Treatment of Dry Eye Disease (COMET-2)

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) for an individual duration of participation of approximately 15 weeks.

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: 0.003% AR-15512 ophthalmic solution; Drug: AR-15512 vehicle ophthalmic solution

Detailed Description

At the end of the Screening Visit, all qualified subjects will be assigned to administer one drop of AR-15512 Vehicle twice a day to both eyes for approximately 14 days (vehicle run-in period). After the vehicle run-in period, subjects will be re-evaluated for signs and symptoms of Dry Eye Disease (DED). Subjects who requalify based on inclusion/exclusion criteria will be enrolled in the study and randomized in a 1:1 ratio to receive 0.003% AR-15512 or AR-15512 Vehicle administered as 1 drop in each eye twice a day for 90 days. At the end of the Day 90 visit, subjects will exit the study.

Aerie Pharmaceuticals was acquired by Alcon on November 22, 2022.

• Study Type: Interventional
• Enrollment (Actual): 465
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 90027
      • Global Research Management, Inc
    • Torrance, California, United States, 90505
      • Premiere Practice Management, LLC
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Vision Institute
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • The Eye Care Group
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Segal Drug Trials, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46240
      • Michael Washburn Center for Ophthalmic Research, LLC
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Butchertown Clinical Trials
  • Maine
    • Lewiston, Maine, United States, 04240
      • Central Maine Eye Care
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • Moyes Eye Center
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Center for Sight
  • North Carolina
    • Shelby, North Carolina, United States, 28150
      • CORE, Inc.
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Bergstrom Eye Research
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Verum Research
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retina Research
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • Advancing Vision Research
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care, PA
    • Smyrna, Tennessee, United States, 37167
      • Advancing Vision Research
  • Texas
    • Austin, Texas, United States, 78750
      • Austin Clinical Research
    • Harlingen, Texas, United States, 78550
      • Valley Retina Institute, PA
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute, PA
    • San Antonio, Texas, United States, 78229
      • R and R Eye Research, LLC
    • San Antonio, Texas, United States, 78209
      • Eye Clinics of South Texas
  • Utah
    • Clinton, Utah, United States, 84015
      • Alpine Research Organization Inc.

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Signs and symptoms of dry eye disease (DED) at the Screening and Baseline visits;
• Corrected visual acuity of +0.70 logarithm Minimum angle of resolution (LogMAR) or better in both eyes at Screening and Baseline visits;
• Other protocol-specified inclusion criteria may apply.

Key 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;
• Medication use as specified in the protocol;
• History or presence of significant systemic disease;
• Other protocol-specified exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.003% AR-15512; 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	Drug: 0.003% AR-15512 ophthalmic solution; Administered via topical ocular instillation
Placebo Comparator: AR-15512 Vehicle; AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days	Drug: AR-15512 vehicle ophthalmic solution; Inactive ingredients administered via topical ocular instillation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 14 in Study Eye Unanesthetized Schirmer Score	The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 14 following drop exposure. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis.	Baseline (Day 1) pre-drop; Day 14 post-drop

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Mean Change From Baseline in Global Symptom Assessment iN Dry Eye (SANDE) Score on Day 28	The SANDE questionnaire assesses the frequency and severity of symptoms using 2 unique, 100 mm Visual Analog Scales to mark the frequency (0=rarely, 100=all the time) and severity (0=very mild, 100=very severe) of dry eye symptoms (prior to drop exposure). The 2 scores were multiplied and a square root was obtained for a resultant overall Global SANDE score of 0 to 100 where 0 represents no symptoms and 100 is maximum symptoms. A negative change indicates a better outcome. This was a subject based assessment (single score for both eyes).	Baseline (Day 1); Day 28
Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 1 (Study Eye)	The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 1 following drop exposure. The Day 1 post-drop score was compared to the Day 1 pre-drop score. A positive change over time indicates a better outcome. One eye (study eye) contributed data to the analysis.	Baseline (Day 1) pre-drop; Day 1 post-drop
Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 90 in Study Eye Unanesthetized Schirmer Score	The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 90 following drop exposure. The Day 90 post-drop score was compared to the Day 1 pre-drop score. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis.	Baseline (Day 1) pre-drop; Day 90 post-drop
Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 90 (Study Eye)	The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 90 following drop exposure. The Day 90 post-drop score was compared to the Day 1 pre-drop score. A positive change over time indicates a better outcome. One eye (study eye) contributed data to the analysis.	Baseline (Day 1) pre-drop; Day 90 post-drop
Least Squares Mean Change From Baseline in SANDE Frequency Score on Day 90	The SANDE questionnaire assesses the frequency of dry eye disease symptoms. Subjects used a 100 mm Visual Analog Scale (VAS) to mark the frequency of symptoms where 0=rarely and 100=all the time. A higher SANDE frequency score indicates greater symptoms of dryness and/or irritation. The questionnaire was completed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.	Baseline (Day 1); Day 90
Least Squares Mean Change From Baseline in SANDE Severity Score on Day 90	The SANDE questionnaire assesses the severity of dry eye disease symptoms. Subjects used a 100 mm Visual Analog Scale (VAS) to mark the severity of symptoms where 0=very mild and 100=very severe. A higher SANDE severity score indicates greater symptoms of dryness and/or irritation. The questionnaire was completed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.	Baseline (Day 1); Day 90
Least Squares Mean Change From Baseline in Eye Dryness Score (EDS) on Day 90	The subject used a 100 mm Visual Analog Scale (VAS) to mark their eye dryness, where 0=no eye dryness and 100=maximum eye dryness. Eye dryness was assessed at Day 1 and Day 90 prior to drop exposure (both visits). A higher eye dryness score indicates greater dryness. The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.	Baseline (Day 1); Day 90
Least Squares Mean Change From Baseline in Ocular Discomfort Score (ODS) on Day 90	The subject used a 100 mm Visual Analog Scale (VAS) to mark their eye dryness, where 0=no ocular discomfort and 100 mm=maximum ocular discomfort. A higher ocular discomfort score indicates greater discomfort. Ocular discomfort was assessed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.	Baseline (Day 1); Day 90
Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 14 (Study Eye)	The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 14 following drop exposure. The Day 14 value was compared to the Day 1 value. A positive change indicates a better outcome. One eye (study eye) contributed data to the analysis.	Baseline (Day 1) pre-drop; Day 14 post-drop
Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 1 in Study Eye Unanesthetized Schirmer Score	The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 1 following drop exposure. The Day 1 post-drop score was compared to the Day 1 pre-drop score. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis.	Baseline (Day 1) pre-drop; Day 1 post-drop
Least Squares Mean Change From Baseline in Global SANDE Score on Day 90	The SANDE questionnaire assesses the frequency and severity of symptoms using 2 unique, 100 mm Visual Analog Scales to mark the frequency (0=rarely, 100=all the time) and severity (0=very mild, 100=very severe) of dry eye symptoms (prior to drop exposure). The 2 scores were multiplied and a square root was obtained for a resultant overall Global SANDE score of 0 to 100 where 0 represents no symptoms and 100 is maximum symptoms. A negative change indicates a better outcome. This was a subject based assessment (single score for both eyes).	Baseline (Day 1); Day 90

Collaborators and Investigators

• Sponsor: Aerie Pharmaceuticals
• Investigators: Study Director: Scientific Advisor, Clinical R&D, Alcon Research, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2022
• Primary Completion (Actual): July 24, 2023
• Study Completion (Actual): July 24, 2023

Study Registration Dates

• First Submitted: March 4, 2022
• First Submitted That Met QC Criteria: March 15, 2022
• First Posted (Actual): March 17, 2022

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Corneal Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Pharmaceutical Solutions; Pharmaceutical Solutions; Ophthalmic Solutions
• Other Study ID Numbers: AR-15512-CS301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No