AR-15512 for Dry Eye Syndrome

No longer recruiting at 5 trial locations

Overseen By Alcon Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alcon Research

Must not be taking: Topical ophthalmic medications

Disqualifiers: Ocular disorders, Ocular surgery, Contact lenses, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 13 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new eye drop, AR-15512, for individuals with dry eye disease (DED). The goal is to determine how effectively these drops improve the eye surface compared to regular artificial tears. Participants will apply one drop in each eye twice daily for 90 days. Suitable candidates have experienced dry eye symptoms and used artificial tears in the past two months. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment for dry eye disease.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using topical medications for other significant eye diseases, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the 0.003% AR-15512 eye drops have not raised any major safety concerns so far. In earlier studies, no serious side effects were reported. This treatment is a new type of eye drop designed to alleviate dry eye symptoms and has been tested in similar trials before. Participants in those trials generally tolerated the treatment well, with most not experiencing severe side effects. For those considering joining a trial for AR-15512, existing evidence suggests it has been safe for others in past studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AR-15512 for treating dry eye syndrome because it offers a potential new way to alleviate symptoms. Unlike standard treatments like artificial tears, which mainly provide temporary relief by lubricating the eyes, AR-15512 targets the TRPM8 receptor. This receptor is involved in the body's natural lubrication and cooling of the eye, potentially offering a more lasting solution by enhancing the eye's own ability to stay moist. This novel mechanism of action is what sets AR-15512 apart and fuels optimism about its effectiveness.

What evidence suggests that this trial's treatments could be effective for dry eye disease?

Research has shown that AR-15512, which participants in this trial may receive, holds promise for treating dry eye syndrome. Studies have found that this treatment can significantly increase tear production, alleviating dry eye symptoms. People who used AR-15512 reported improvements in both the signs and symptoms of dry eye. Reports also indicate quick and lasting tear production, offering hope for those with long-term dry eye. Overall, based on these findings, AR-15512 appears to be an effective option for managing dry eye syndrome. ^{2 5 6 7 8}

Who Is on the Research Team?

Clinical Trial Lead, Pharma

Principal Investigator

Alcon Research, LLC

Are You a Good Fit for This Trial?

This trial is for individuals with dry eye disease. Participants should have a diagnosis of dry eye syndrome and be willing to follow the study procedures. Specific eligibility criteria are not provided, but typically include age limits, symptom severity, and no recent use of conflicting medications or treatments.

Inclusion Criteria

Good general and ocular health, as determined by the investigator using medical history, ophthalmic examination and history

Other protocol specified inclusion criteria may apply

I have been diagnosed with or reported dry eye disease in the last 6 months.

Exclusion Criteria

I do not have any eye diseases that need drops or could affect the study.

I haven't had any lid heating or Meibomian gland treatments in the last year.

I regularly use lid hygiene or heat masks and plan to continue during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in

Qualified subjects will enter a 14-day run-in period, administering Artificial Tears (REFRESH® Classic) as one drop in each eye twice daily

2 weeks

Treatment

Participants receive either 0.003% AR-15512 or Artificial Tears, one drop in each eye twice daily for 90 days

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 0.003% AR-15512
• Artificial Tears

Trial Overview The study is testing the effectiveness of a new ophthalmic solution called AR-15512 at a concentration of 0.003%. It's being compared against artificial tears, which are commonly used to manage symptoms of dry eye disease.

How Is the Trial Designed?

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

One drop in each eye twice daily for 90 days (treatment period)

Group II: Artificial Tears Active Control 1 Intervention

One drop in each eye twice daily for 90 days (treatment period)

Who Is Running the Clinical Trial?

Alcon Research

Lead Sponsor

Trials

739

Recruited

128,000+

Raquel C. Bono

Alcon Research

Chief Medical Officer since 2022

MD from Harvard Medical School

David Endicott

Alcon Research

Chief Executive Officer since 2018

MBA from University of Southern California

Published Research Related to This Trial

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]

In a study of 16,862 patients receiving ocular care at Veterans Affairs clinics, the prevalence of dry eye syndrome (DES) was found to be 12% in men and 22% in women, with female patients having a 2.40 times higher risk than male patients.

The study identified several medical conditions, such as post-traumatic stress disorder, depression, thyroid disease, and sleep apnea, as significant risk factors for developing DES, along with the use of certain medications like antidepressants and anti-anxiety drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and risk factors of dry eye syndrome in a United States veterans affairs population. Galor, A., Feuer, W., Lee, DJ., et al.[2022]

The prevalence of symptomatic dry eye disease (SDED) in Singapore is 12.3%, with a higher occurrence in females compared to males.

Key risk factors for SDED include contact lens wear, previous treatment for dry eye, certain medications, unusual eye sensitivity, constant mucous membrane dryness, and irritation upon waking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of and risk factors for symptomatic dry eye disease in Singapore. Tan, LL., Morgan, P., Cai, ZQ., et al.[2015]

Ion channels on the ocular surface, including chloride and purinergic receptors, play a crucial role in the development of dry eye, highlighting their potential as therapeutic targets.

Research into channel-targeting compounds has shown promising results in both laboratory and clinical settings, suggesting that these compounds could lead to effective treatments for dry eye.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocular Surface Ion-Channels Are Closely Related to Dry Eye: Key Research Focus on Innovative Drugs for Dry Eye. Yang, S., Wu, Y., Wang, C., et al.[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]

In a study of 295 individuals, the implementation of new dry eye diagnostic criteria in Japan led to a reclassification of many patients, with 31.7% of those previously diagnosed with probable dry eye (PDE) now classified as normal.

The new criteria resulted in a significant shift in diagnostic status, indicating that patients with more severe dry eye disease are now more accurately diagnosed as having definite dry eye (DDE), while the overall severity scores remained unchanged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in dry eye diagnostic status following implementation of revised Japanese dry eye diagnostic criteria. Uchino, Y., Uchino, M., Dogru, M., et al.[2021]

In a study of 270 patients over 50 years old in Valladolid, Spain, the prevalence of dry eye syndrome (DES) was found to be 24.2% based on a combination of Schirmer and tear break-up time tests.

The modified McMonnies (Q1) and Ocular Surface Index (Q2) questionnaires were found to be unreliable for diagnosing DES, showing poor internal consistency and no correlation with objective diagnostic tests, while fluorescein and Rose Bengal staining were the most reliable methods for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lack of concordance between dry eye syndrome questionnaires and diagnostic tests]. Fuentes-Páez, G., Herreras, JM., Cordero, Y., et al.[2019]

In a study of 2619 individuals with symptomatic dry eye in Japan, 1876 participants did not use any eye drops, highlighting a significant gap in treatment for this condition.

The most commonly used eye drops were artificial tears (53.4%), but various risk factors, such as age and screen exposure time, were identified that contributed to the lack of eye drop use, suggesting areas for targeted intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneity of eye drop use among symptomatic dry eye individuals in Japan: large-scale crowdsourced research using DryEyeRhythm application. Eguchi, A., Inomata, T., Nakamura, M., et al.[2021]

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]

SA001, a new formulation of rebamipide, showed significantly higher systemic exposure of rebamipide compared to conventional rebamipide, with plasma concentrations up to 11.94 times higher at the highest dose, indicating enhanced efficacy potential for treating dry eye disease.

The study demonstrated that SA001 was rapidly absorbed and well-tolerated, with no significant adverse events reported, supporting its safety for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Safety, Tolerability and Pharmacokinetic Characteristics of SA001 and Its Active Metabolite Rebamipide after Single and Multiple Oral Administration. Bae, S., Huh, KY., Oh, J., et al.[2023]

Iatrogenic dry eye disease (DED) can result from various medical and cosmetic interventions, including topical medications, systemic drugs, and surgical procedures like LASIK, which can damage corneal nerves and lead to patient dissatisfaction and poor outcomes.

To mitigate the risk of iatrogenic DED, future efforts should focus on developing less toxic medications, improving surgical techniques, and conducting more epidemiological studies to better understand the risk factors associated with DED.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TFOS DEWS II iatrogenic report. Gomes, JAP., Azar, DT., Baudouin, C., et al.[2022]

OC-01 (varenicline solution nasal spray) significantly improved tear production and symptoms in patients with dry eye disease, showing consistent efficacy across various demographic groups including age, gender, and race, based on data from 602 participants in two clinical trials.

The treatment's effectiveness was not influenced by the use of artificial tears, indicating that OC-01 VNS can be beneficial for a wide range of patients regardless of their prior treatment with artificial tears.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OC-01 (Varenicline Solution) Nasal Spray Demonstrates Consistency of Effect Regardless of Age, Race, Ethnicity, and Artificial Tear Use. Epitropoulos, AT., Daya, SM., Matossian, C., et al.[2022]

Citations

1. 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 ... The participants in the AR-15512 treatment arm also showed rapid onset and sustained tear production compared to the vehicle. The changes in ...

2. 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 ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05360966

Study Evaluating the Safety and Efficacy of AR-15512 ... This will be a Phase 3, multicenter, vehicle-controlled, double-masked, randomized study conducted at approximately 20 sites in the United States.

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06660290

A Study to Evaluate 0.003% AR-15512 Safety and Drop ... Corrected Visual Acuity (Snellen) 20/200 or better in both eyes; · Good general and ocular health, as determined by the Investigator using medical history, ...

7. 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.

8. malacards.org malacards.org/card/keratoconjunctivitis_sicca

Keratoconjunctivitis Sicca (KCS) SHR8028 eye drops; Vehicle eye drops. 292, A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512, a Cold Thermoreceptor Modulator, ...