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).

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: Vehicle; Drug: AR 15512 Ophthalmic Solution

• 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 Surgery
  • 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

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 solution 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 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unanesthetized Schirmer test	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.	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SANDE (Symptom Assessment iN Dry Eye) Questionnaire Score	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.	Day 28
Unanesthetized Schirmer score	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.	Day 7, 14, 28 & 90
Ocular Discomfort Score (ODS) - VAS	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.	Day 28 & 90
Eye Dryness Score (EDS) - VAS	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.	Day 28 & 90
Unanesthetized Schirmer score	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.	Day 7, 28 & 90
Quality of Life VAS	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.	Day 7, 14, 28 & 90
Conjunctival Redness	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.	Day 90
SANDE (Symptom Assessment iN Dry Eye) Questionnaire Score	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.	Day 7, 14 & 90
Ocular Pain - VAS	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.	Day 90

Collaborators and Investigators

• Sponsor: Aerie Pharmaceuticals
• Investigators: Study Director: Michelle Senchyna, PhD, Aerie Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2022
• Primary Completion (Actual): July 21, 2023
• Study Completion (Actual): July 21, 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): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 7, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; 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