NCT05285644: COMET-2

Study Evaluating the Safety and Efficacy of AR-15512

Completed Phase 3 Results posted Last updated 23 July 2025

What this trial tests

Phase 3 trial testing 0.003% AR-15512 ophthalmic solution in Dry Eye Disease in 465 participants. Completed in 24 July 2023.

Timeline

9 May 2022

Primary endpoint
24 July 2023

24 July 2023

Quick facts

Lead sponsor	Aerie Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	465
Start date	9 May 2022
Primary completion	24 July 2023
Estimated completion	24 July 2023
Sites	23 locations across United States

Drugs / interventions tested

• 0.003% AR-15512 ophthalmic solution — full drug profile →
• AR-15512 vehicle ophthalmic solution — full drug profile →

Conditions studied

• Dry Eye Disease — all drugs for Dry Eye Disease →

Sponsor

Aerie Pharmaceuticals — full company profile →

Who can join

30 and older, any sex, with Dry Eye Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Baseline (Day 1) pre-drop; Day 14 post-drop

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.

Group	Value	95% CI
0.003% AR-15512	42.6
AR-15512 Vehicle	8.2

Least Squares Mean Change From Baseline in Global Symptom Assessment iN Dry Eye (SANDE) Score on Day 28 Secondary · Baseline (Day 1); 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).

Group	Value	95% CI
0.003% AR-15512	-19.7	± 1.61
AR-15512 Vehicle	-14.7	± 1.58

Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 14 (Study Eye) Secondary · Baseline (Day 1) pre-drop; Day 14 post-drop

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.

Group	Value	95% CI
0.003% AR-15512	9.8	± 0.55
AR-15512 Vehicle	2.6	± 0.54

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 Secondary · Baseline (Day 1) pre-drop; Day 1 post-drop

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.

Group	Value	95% CI
0.003% AR-15512	36.1
AR-15512 Vehicle	9.4

Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 1 (Study Eye) Secondary · Baseline (Day 1) pre-drop; Day 1 post-drop

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.

Group	Value	95% CI
0.003% AR-15512	8.9	± 0.53
AR-15512 Vehicle	2.7	± 0.52

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 Secondary · Baseline (Day 1) pre-drop; Day 90 post-drop

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.

Group	Value	95% CI
0.003% AR-15512	46.7
AR-15512 Vehicle	13.6

Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 90 (Study Eye) Secondary · Baseline (Day 1) pre-drop; Day 90 post-drop

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.

Group	Value	95% CI
0.003% AR-15512	10.7	± 0.59
AR-15512 Vehicle	3.1	± 0.57

Least Squares Mean Change From Baseline in Global SANDE Score on Day 90 Secondary · Baseline (Day 1); 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).

Group	Value	95% CI
0.003% AR-15512	-23.5	± 1.78
AR-15512 Vehicle	-20.7	± 1.77

Least Squares Mean Change From Baseline in SANDE Frequency Score on Day 90 Secondary · Baseline (Day 1); 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.

Group	Value	95% CI
0.003% AR-15512	-22.8	± 1.89
AR-15512 Vehicle	-20.1	± 1.89

Least Squares Mean Change From Baseline in SANDE Severity Score on Day 90 Secondary · Baseline (Day 1); 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.

Group	Value	95% CI
0.003% AR-15512	-23.1	± 1.87
AR-15512 Vehicle	-20.5	± 1.84

Least Squares Mean Change From Baseline in Eye Dryness Score (EDS) on Day 90 Secondary · Baseline (Day 1); 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.

Group	Value	95% CI
0.003% AR-15512	-22.5	± 1.89
AR-15512 Vehicle	-19.1	± 1.84

Least Squares Mean Change From Baseline in Ocular Discomfort Score (ODS) on Day 90 Secondary · Baseline (Day 1); 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.

Group	Value	95% CI
0.003% AR-15512	-32.2	± 2.06
AR-15512 Vehicle	-28.2	± 2.04

Adverse events — posted to ClinicalTrials.gov

Time frame: An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 15 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pretreatment

Serious: 1/465 (0%)

Deaths: 0/465

0.003% AR-15512 Ocular

Serious: 0/230 (0%)

Deaths: 0

0.003% AR-15512 Nonocular

Serious: 1/230 (0%)

Deaths: 0/230

AR-15512 Vehicle Ocular

Serious: 0/235 (0%)

Deaths: 0

AR-15512 Vehicle Nonocular

Serious: 6/235 (3%)

Deaths: 0/235

Serious adverse events (11 terms)

Reaction	System	Pretreatment	0.003% AR-15512 Ocular	0.003% AR-15512 Nonocular	AR-15512 Vehicle Ocular	AR-15512 Vehicle Nonocular
Coronary artery occlusion	Cardiac disorders	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Haemorrhoidal haemorrhage	Gastrointestinal disorders	—	—	—	—	—
Volvulus	Gastrointestinal disorders	—	—	—	—	—
Norovirus infection	Infections and infestations	—	—	—	—	—
Pneumonia influenzal	Infections and infestations	—	—	—	—	—
Cartilage injury	Injury, poisoning and procedural complications	—	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—	—
Seizure	Nervous system disorders	—	—	—	—	—
Alcohol withdrawal syndrome	Psychiatric disorders	—	—	—	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Pretreatment	0.003% AR-15512 Ocular	0.003% AR-15512 Nonocular	AR-15512 Vehicle Ocular	AR-15512 Vehicle Nonocular
Instillation site pain	General disorders	—	—	—	—	—

Most-reported serious reactions: Coronary artery occlusion, Constipation, Haemorrhoidal haemorrhage, Volvulus, Norovirus infection, Pneumonia influenzal, Cartilage injury, Breast cancer.

Data from ClinicalTrials.gov NCT05285644 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Acoltremon Ophthalmic Solution 0.003% for Signs and Symptoms of Dry Eye Disease: Results of Phase 3 Pivotal COMET-2 and COMET-3 Studies.
   Pattar GR, Wirta D, Jerkins G, Paauw J, et al · · 2026 · cited 4× · PMID 41038456 · DOI 10.1016/j.ophtha.2025.09.018
2. Matching-adjusted indirect comparison of acoltremon ophthalmic solution 0.003% and cyclosporine 0.05% ophthalmic emulsion for increased tear production in patients with dry eye disease.
   Pflugfelder S, Okoro T, Ainslie-Garcia M, Haltner A, et al · · 2026 · PMID 42132429 · DOI 10.57264/cer-2026-0032