A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (COMET-4)

November 10, 2023 updated by: Aerie Pharmaceuticals

A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512, a Cold Thermoreceptor Modulator, for the Treatment of Dry Eye Disease (COMET-4)

This will be a 12-month, multicenter, vehicle-controlled, double-masked, randomized Phase 3 study conducted at approximately 10 sites in the United States. All subjects enrolled will have dry eye disease (DED). The study will consist of a Baseline (Day 1) visit as well as visits at Day 14, Day 90, Day 180, Day 270, and Day 365 (Study Exit).

Study Overview

Status

Active, not recruiting

Conditions

Study Type

Interventional

Enrollment (Actual)

275

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arizona
      • Chandler, Arizona, United States, 85225
        • Arizona Eye Center
      • Sun City, Arizona, United States, 85351
        • PRG - Arizona Eye Institute
    • California
      • Glendale, California, United States, 91204
        • Global Research Management
      • Los Angeles, California, United States, 90048
        • Macy Eye Center
      • Newport Beach, California, United States, 92663
        • Eye Research Foundation
      • Northridge, California, United States, 91325
        • Shultz Vision
    • New York
      • Manhasset, New York, United States, 11030
        • SightMD
    • Tennessee
      • Maryville, Tennessee, United States, 37803
        • University Eye Specialists
    • Virginia
      • Lynchburg, Virginia, United States, 24502
        • Piedmont Eye Center
    • Washington
      • Seattle, Washington, United States, 98119
        • Periman Eye Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Male or female, 18 years of age or older at baseline visit
  • Have a previous history of DED, clinician diagnosed or patient reported, within the previous 12 months of the Baseline visit
  • Have used or desired to use artificial tears for DED symptoms within 3 months prior to the Baseline visit
  • Have a documented Schirmer test with or without topical anesthesia score ≥ 2 and < 10 mm/5 min in at least one eye within 1 year prior to the Baseline visit
  • Total ocular surface staining score of ≥ 1 and ≤ 12 and no region = 5, based on the Oxford grading scheme at the Baseline visit
  • Corrected visual acuity equal to or better than logMar +0.7 (Snellen equivalent equal to or better than 20/100), as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in both eyes at the Baseline visit
  • Good general and ocular health, as determined by the investigator using medical history, ophthalmic examination and history, and vital signs (heart rate and blood pressure) at the Baseline visit

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
  • 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
  • Use of contact lenses in either eye within 7 days prior to the Baseline visit or planned use during the study
  • Use of any topical ocular anti-inflammatory medication within 30 days prior to the Baseline 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 topical ocular autologous serum within 30 days prior to the Baseline visit or anticipated use during the study
  • Use of any topical ocular glaucoma medication within 30 days prior to the Baseline visit or anticipated use during the study
  • Use of Tyrvara™ (varenicline solution, nasal spray 0.03mg) within 30 days prior to the Baseline 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 Baseline visit or anticipated use during the study
  • Use of lid heating therapy (i.e., LipiFlow®, iLUX®) or Meibomian gland probing/therapeutic expression within 6 months prior to the Baseline visit or anticipated during the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AR-15512 Ophthalmic Solution (0.003%)
0.003% AR-15512 to be administered BID for 365 days. Both eyes will be treated.
Topical ocular administration of one drop in both eyes BID for 365 days.
Placebo Comparator: Vehicle
AR-15512 vehicle to be administered BID for 365 days. Both eyes will be treated.
Topical ocular administration of one drop in both eyes BID for 365 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: Day 1, 14, 90, 180, 270 & 365

Incidence of Adverse Events

Subjects will be verbally asked by clinic staff to report any changes to any aspect of their health (systemic or ocular) at each study visit. A low incidence indicates a better outcome.

Day 1, 14, 90, 180, 270 & 365
Blood Pressure
Time Frame: Day 1, 14, 90, 180, 270 & 365

Change from baseline

Each subjects systolic and diastolic blood pressure will be measured using an appropriate sphygmomanometer and will be recorded in mmHg. Minimal change from the start of the study indicates a better outcome.

Day 1, 14, 90, 180, 270 & 365
Heart Rate
Time Frame: Time Frame: Day 1, 14, 90, 180, 270 & 365

Change from Baseline

Each subjects heart rate will be measured using manual or automated methods and recorded in bpm. Minimal change from the start of the study indicates a better outcome.

Time Frame: Day 1, 14, 90, 180, 270 & 365
Endothelial cell counts
Time Frame: Day 1 and 365

Change from baseline

Specular microscopy will be used to measure cells in the central cornea to determine cell density which will be recorded. Minimal change from the start of the study indicates a better outcome.

Day 1 and 365
Hematology, chemistry, and urinalysis
Time Frame: Day 1, 180 & 365

Change from baseline

A small volume of blood and urine will be collected from each subject and these samples will be sent to a laboratory to evaluate each subjects overall health. Values for each assessment will be recorded in their respective clinical units. Minimal change from the start of the study indicates a better outcome.

Day 1, 180 & 365
LogMAR Visual Acuity
Time Frame: Day 1, 14, 90, 180, 270 & 365

Change from baseline

Each subject's vision will be assessed using an eye chart and the score will be recorded as the number of letters read. If a subject wears glasses, these will be worn during the test. Minimal change from the start of the study indicates a better outcome.

Day 1, 14, 90, 180, 270 & 365
Early Treatment of Diabetic Retinopathy Study (ETDRS) Visual Acuity
Time Frame: Day 1 & 365

Change from baseline

Change from baseline Each subject's vision will be assessed using a standardized eye chart and ETDRS testing procedure. The score will be recorded as the number of letters read. Minimal change from the start of the study indicates a better outcome.

Day 1 & 365
Biomicroscopy
Time Frame: Day 1, 14, 90, 180, 270 & 365

Change from baseline

With the aid of a microscope, the front part of the eyes and eyelids and the surface of the cornea will be examined and graded based on standard clinical scales and recorded as normal or abnormal. Minimal change from the start of the study indicates a better outcome.

Day 1, 14, 90, 180, 270 & 365
Total ocular staining
Time Frame: Day 1, 14, 90, 180, 270 & 365

Change from baseline

Dye is applied to the surface of the eye and the amount of dye that remains after several minutes will viewed through a microscope and graded using a standardized scale (0-5). Lower scores indicate a better outcome.

Day 1, 14, 90, 180, 270 & 365
Intraocular pressure (IOP)
Time Frame: Day 1, 14, 90, 180, 270 & 365

Change from baseline

A small tonometer device will be pressed against the surface of the eye to determine the pressure inside the eye. The pressure will be recorded in mmHg. Lower scores indicate a better outcome.

Day 1, 14, 90, 180, 270 & 365
Dilated fundus exam
Time Frame: Day 1, 14, 90, 180, 270 & 365

Change from baseline

The back of the eyes will be dilated, examined and graded based on standard clinical scales and recorded as normal or abnormal. Minimal change from the start of the study indicates a better outcome

Day 1, 14, 90, 180, 270 & 365

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimum Plasma Concentration (Cmin)
Time Frame: Day 1, 14 and 90
From the blood samples collected from each subject, the minimum amount of AR-15512, the test drug, that may be present in the blood will be measured at a laboratory. Each measure will be recorded in pg/ml. Lower numbers represent better outcome.
Day 1, 14 and 90
Accumulation Ratio (Rcmax)
Time Frame: Day 1, 14 and 90
From the blood samples collected from each subject, the amount of AR-15512, the test drug, that may have accumulated in the blood will be measured in a laboratory. Each measure will be recorded as a number based on a ratio (e.g. Cmax Day 90 / Cmax Day 1). Lower numbers represent better outcome.
Day 1, 14 and 90
Time to Maximum Concentration (Tmax)
Time Frame: Day 1, 14 and 90
From the blood samples collected from each subject, the time at which the highest amount of AR-15512, the test drug, is measured in the blood will be measured in a laboratory. Each measure will be recorded in hours/min/sec.
Day 1, 14 and 90
Time to Last Detectable Concentration (Tlast)
Time Frame: Day 1, 14 and 90
From the blood samples collected from each subject, the time at which the last detectable amount of AR-15512, the test drug, is measured in the blood will be measured in a laboratory. Each measure will be recorded in hours/min/sec. Lower number represents better outcome.
Day 1, 14 and 90
Total Exposure (AUC0-last)
Time Frame: Day 1, 14 and 90
From the blood samples collected from each subject, the overall amount of AR-15512, the test drug, in the blood from the start of dose administration to the time after dosing at which the last quantifiable concentration was observed will be measured in a laboratory. Each measure will be recorded in µg*h/L. Lower numbers represent better outcome.
Day 1, 14 and 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Michelle Senchyna, PhD, Aerie Pharma

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2022

Primary Completion (Estimated)

March 31, 2024

Study Completion (Estimated)

March 31, 2024

Study Registration Dates

First Submitted

July 26, 2022

First Submitted That Met QC Criteria

August 5, 2022

First Posted (Actual)

August 9, 2022

Study Record Updates

Last Update Posted (Actual)

November 13, 2023

Last Update Submitted That Met QC Criteria

November 10, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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