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

• ClinicalTrials.gov Identifier: NCT05493111
• Recruitment Status: Completed
• First Posted: August 9, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Aerie Pharmaceuticals
• Information provided by (Responsible Party): Aerie Pharmaceuticals

Study Description

Brief Summary:

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).

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)
• Actual Enrollment: 275 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Qualified subjects will be enrolled in the study and randomized in a 2:1 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 365 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 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)
• Actual Study Start Date: November 1, 2022
• Actual Primary Completion Date: February 28, 2024
• Actual Study Completion Date: February 28, 2024

Arms and Interventions

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.	Drug: AR-15512 Ophthalmic Solution; 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.	Drug: Vehicle; Topical ocular administration of one drop in both eyes BID for 365 days.

Outcome Measures

Primary Outcome Measures :

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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

Other Outcome Measures:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Arizona Eye Center

Chandler, Arizona, United States, 85225

PRG - Arizona Eye Institute

Sun City, Arizona, United States, 85351

United States, California

Global Research Management

Glendale, California, United States, 91204

Macy Eye Center

Los Angeles, California, United States, 90048

Eye Research Foundation

Newport Beach, California, United States, 92663

Shultz Vision

Northridge, California, United States, 91325

United States, New York

SightMD

Manhasset, New York, United States, 11030

United States, Tennessee

University Eye Specialists

Maryville, Tennessee, United States, 37803

United States, Virginia

Piedmont Eye Center

Lynchburg, Virginia, United States, 24502

United States, Washington

Periman Eye Institute

Seattle, Washington, United States, 98119

Sponsors and Collaborators

Aerie Pharmaceuticals

Investigators

• Study Director: Michelle Senchyna, PhD; Aerie Pharma

More Information

• Responsible Party: Aerie Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05493111
• Other Study ID Numbers: AR-15512-LTSS
• First Posted: August 9, 2022
• Last Update Posted: April 24, 2024
• Last Verified: April 2024

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