AR-15512 for Dry Eye Syndrome

(COMET-4 Trial)

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

275 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment for people with dry eye disease. Participants will receive the new treatment to see if it works better than no 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.

What data supports the effectiveness of the drug AR-15512 for treating dry eye syndrome?

The study titled '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)' suggests that AR-15512, which targets a specific receptor in the eye, was evaluated as a potential therapy for dry eye disease, indicating its potential effectiveness. ^{1 2 3 4 5}

How is the drug AR-15512 different from other dry eye treatments?

AR-15512 is unique because it works by activating the TRPM8 receptor, which is involved in sensing cold and menthol, potentially providing a new way to relieve dry eye symptoms by stimulating tear production and cooling the eye surface. ^{4 6 7 8 9}

Research Team

Sr. Fellow, Clinical Research

Principal Investigator

Alcon Research, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ocular iontophoresis of EGP-437 (dexamethasone phosphate) in dry eye patients: results of a randomized clinical trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Changes in Distribution of Dry Eye Disease by the New 2016 Diagnostic Criteria from the Asia Dry Eye Society. [2019]

3. England pubmed.ncbi.nlm.nih.gov

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

4. United States 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). [2022]

5. United States pubmed.ncbi.nlm.nih.gov

New testing options for diagnosing and grading dry eye disease. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

The Efficacy of Diquafosol Ophthalmic Solution in Non-Sjögren and Sjögren Syndrome Dry Eye Patients Unresponsive to Artificial Tear. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Lifitegrast Ophthalmic Solution 5%: A Review in Dry Eye Disease. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Diquafosol tetrasodium: a novel dry eye therapy. [2019]