AR-15512 for Dry Eye Syndrome

(COMET-4 Trial)

No longer recruiting at 10 trial locations

Overseen By Richard Coles

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Aerie Pharmaceuticals

Disqualifiers: Glaucoma, Cataract, Macular degeneration, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new eye drop, AR-15512, for individuals with Dry Eye Disease (DED). Participants will use either AR-15512 drops or a placebo (a look-alike solution with no active medicine) twice daily for a year. It suits those who have struggled with dry eyes in the past year and have used or wanted to use artificial tears recently. The study aims to determine if AR-15512 is a safe and effective treatment for easing dry eye symptoms. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol mentions that certain medications are specified, but it does not provide details on which ones. It's best to discuss your current medications with the study team to see if any need to be stopped.

Is there any evidence suggesting that AR-15512 Ophthalmic Solution is likely to be safe for humans?

Research has shown that AR-15512 is generally well-tolerated. In one study, participants reported no serious eye-related side effects, suggesting the treatment is safe for humans. Additionally, no major safety concerns have been identified, indicating that most users of AR-15512 did not experience harmful effects. Overall, based on previous studies, the treatment appears safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for dry eye syndrome, such as artificial tears and anti-inflammatory medications like cyclosporine, AR-15512 is unique because it utilizes a novel approach targeting the TRPM8 receptor. This receptor is involved in cold sensation and plays a role in tear production. By activating TRPM8, AR-15512 aims to increase natural tear production, potentially offering a more direct and effective relief for dry eye symptoms. Researchers are excited because this mechanism could provide a refreshing alternative to existing therapies, which often require long-term use and may not address the underlying causes of dryness.

What evidence suggests that AR-15512 might be an effective treatment for dry eye disease?

Research has shown that AR-15512 Eye Drops relieve dry eye symptoms. Studies have found that they increase tear production and reduce discomfort. In two large studies, AR-15512 met its main goals, demonstrating clear benefits for people with dry eye. Participants in this trial may receive either the 0.003% AR-15512 ophthalmic solution or a placebo comparator. Previous users reported a better quality of life and fewer signs of dry eye. This treatment offers a promising option for those dealing with dry eye problems. ^{4 5 6 7 8}

Who Is on the Research Team?

Scientific Advisor, CRD

Principal Investigator

Alcon Research, LLC

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a history of Dry Eye Disease (DED) within the last year, who have certain levels of eye surface staining and tear production. Participants should be in good general and ocular health but cannot use contact lenses or any topical eye treatments for DED or glaucoma recently.

Inclusion Criteria

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

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

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

Exclusion Criteria

I don't have any eye conditions that could affect this study's results or my safety.

I have used or plan to use eye drops made from my own blood in the last 30 days or during the study.

I haven't used any eye drops for glaucoma in the last 30 days and won't use them during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Washout

Subjects undergo a protocol-specified washout period for prohibited prior and concomitant therapies

2 weeks

Treatment

Participants receive 0.003% AR-15512 or AR-15512 Vehicle administered as 1 drop in each eye twice a day

52 weeks

Visits on Days 1, 14, 45, 90, 135, 180, 225, 270, 315, and 365

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AR-15512 Ophthalmic Solution

Trial Overview The study tests AR-15512 Ophthalmic Solution against a placebo (vehicle) over 12 months to evaluate its long-term safety in treating DED. Patients will visit clinics at set intervals after starting treatment to monitor effects.

How Is the Trial Designed?

Group I: 0.003% AR-15512 Experimental Treatment 1 Intervention

0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 365 days

Group II: AR-15512 Vehicle Placebo Group 1 Intervention

AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 365 days

Who Is Running the Clinical Trial?

Aerie Pharmaceuticals

Lead Sponsor

Trials

39

Recruited

8,300+

Published Research Related to This Trial

Dry eye syndrome is a common but often underdiagnosed condition that can lead to chronic pain and increased risk of ocular surface disease, highlighting the need for greater awareness and appropriate interventions.

Experts recommend using preservative-free artificial tear products as the first-line treatment for all levels of dry eye, as they are safer and more effective for patients, ensuring better ocular surface health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing importance of dry eye syndrome and the ideal artificial tear: consensus views from a roundtable discussion. Asbell, PA.[2022]

Recent advancements in technology have significantly improved the diagnosis and grading of dry eye disease by allowing for noninvasive measurements of tear stability, composition, and meniscus height.

Tests like tear osmolarity and imaging are becoming standard in clinical practice, offering more sensitivity and reliability compared to traditional methods, which may lead to better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New testing options for diagnosing and grading dry eye disease. Foulks, GN., Pflugfelder, SC.[2022]

In a Phase 2b study involving patients with dry eye disease, the 0.003% concentration of AR-15512 showed significant improvements in eye symptoms and quality of life measures over 12 weeks, particularly at Days 14, 28, and 84.

While the study did not meet its predefined co-primary endpoints, AR-15512 was associated with early and sustained improvements in eye surface health and symptoms, with the most common side effects being mild burning and stinging upon application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, vehicle-controlled, Phase 2b study of two concentrations of the TRPM8 receptor agonist AR-15512 in the treatment of dry eye disease (COMET-1). Wirta, DL., Senchyna, M., Lewis, AE., et al.[2022]

The reclassification of dry eye disease (DED) patients from the 2006 to the 2016 diagnostic criteria resulted in a significant increase in the prevalence of definite DED, from 38.8% to 66.8% among 250 patients studied.

Most patients previously classified as having probable DED (79.8%) were reclassified as having definite DED under the new criteria, indicating a shift in how DED is diagnosed and potentially affecting treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in Distribution of Dry Eye Disease by the New 2016 Diagnostic Criteria from the Asia Dry Eye Society. Inomata, T., Shiang, T., Iwagami, M., et al.[2019]

Citations

1. alcon.com alcon.com/media-release/alcon-announces-positive-topline-results-phase-3-comet-trials-ar-15512-novel-topical/

Alcon Announces Positive Topline Results From Phase 3 ... AR-15512 demonstrated this important achievement in both pivotal efficacy and safety studies and it represents a first-in-class candidate for chronic dry eye.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05285644

Study Evaluating the Safety and Efficacy of AR-15512 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35970431/

A randomized, vehicle-controlled, Phase 2b study of two ... AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related QoL.

4. clinicaltrialsarena.com clinicaltrialsarena.com/news/alcons-dry-eye-drug-achieves-primary-endpoints-in-phase-iii-trials/

Alcon's dry eye drug achieves primary endpoints in Phase ... Switzerland-based Alcon's dry eye disease drug AR-15512 achieved primary endpoints in two Phase III trials, COMET-2 and COMET-3.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0161642025006050

Acoltremon Ophthalmic Solution 0.003% for Signs and ... In both phase 3 studies, ACO compared with VEH led to consistent, clinically meaningful tear production as well as reductions in other DED signs ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/217370Orig1s000RiskR.pdf

217370Orig1s000 - accessdata.fda.gov The applicant was informed that based on the currently available data, no significant safety concerns had been identified to date. 3.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05285644

Study Evaluating the Safety and Efficacy of AR-15512 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 ...

8. withpower.com withpower.com/trial/phase-3-dry-eye-syndromes-9-2024-e76ad

AR-15512 for Dry Eye Syndrome · Info for Participants The safety data for AR-15512 in treating dry eye syndrome is available from a Phase 2b study (COMET-1) that evaluated two concentrations of AR-15512, ...