Effect of Acoltremon Ophthalmic Solution 0.003% on Signs and Symptoms of Ocular Surface Disease in Stage I Neurotrophic Keratopathy Patients With Tear Deficiency

Overview

STUDY OBJECTIVE To assess if acoltremon 0.003% improves tear production in patients with Stage 1 Neurotrophic Keratopathy.

Detailed description

This study is designed to provide clinical data on how acoltremon ophthalmic solution 0.003% affects tear production in subjects with stage I neurotrophic keratopathy (NK). The study drug, Acoltremon, is formulated to help increase tear production. Since the tissue breakdown of the cornea is causing NK, it is thought that this study treatment may help participants with this disease by enhancing wound healing, repair and regeneration through improving nerve function of the cornea.

Participants will be followed for 8 weeks, evaluating unanesthetized Schirmer test score between 3 minutes post-drop week 8 compared to pre-drop at baseline (day 1), their mean change in Best Corrected distance visual acuity (ETDRS standards) from day 1 to week 8, and change in central corneal staining from baseline to week 8.

Interventions

• Drug Patients will receive topical Acoltremon 0.003% ophthalmic solution BID in both eyes over an 8 week period.
  This is an FDA approved drug. The participants will be educated on the potential instillation site sensation that may occur as reported from the Pivotal Trials and that the sensation may differ between eyes due to the Neurotrophic Keratopathy. Qualified eyes must meet the inclusion and exclusion criteria. If both eyes qualify, then the one with the worst vision will be the study eye. If both eyes have equal visual acuity then the right eye will be the study eye.
• Other Alternative would be patient exiting the trial and starting on tears or other standard of care.
  This is an open label trial. If the patient does not do well on Acoltremon Ophthalmic Solution, then the participant will be removed from trial and put on standard of care treatment, other than Acoltremon.

Primary outcome measures

• Unanesthetized Schirmer Test [Time frame: 8 weeks]

Secondary outcome measures (1)

• Unanesthetized Schirmer test [Time frame: 1 Day]

Eligibility criteria

Inclusion criteria

• Neurotrophic Keratopathy stage 1 diagnosis based on the following: Presence of 3+ fluorescein staining in central cornea and decreased corneal sensation (Cochet-Bonnet less than 4cm in the central cornea)
• Baseline unanesthetized Schirmer's test ≤ 10 mm
• Females of childbearing potential must have a negative pregnancy test.
• Best corrected distance visual acuity (BCDVA), using corrective lenses, if necessary, in the study eye of at least +1.0 Log MAR (Snellen <20/200).

Exclusion criteria

• Evidence of any active ocular infection or any intraocular inflammation.
• Evidence of any persistent epithelial defect/ulcer or any corneal scar/corneal edema.
• Presence of any other ocular conditions that require topical medications during the treatment phase.
• History of severe systemic allergies or severe ocular allergies.
• Inability to suspend topical medications 8 days prior to the starting date and artificial tears 2 hours prior to the first study visit and remain off for the duration of the study.
• History of any ocular surgery within three months before study visit 1.
• Ocular surgery expected during the duration of the study.
• Use of refractive/therapeutic contact lenses during the study period.
• Female subjects who are pregnant/have a positive pregnancy test result or are breastfeeding or intend to become pregnant during the study treatment period.
• Drug addiction/alcohol abuse.
• Participation in another clinical trial concurrently

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of South Florida/Ophthalmology — Tampa

Publications

• Khalid M, Zahid E, Shaheer M. "Acoltremon: a novel advancement in dry eye disease management". Ann Med Surg (Lond). 2025 Oct 17;87(12):9121-9122. doi: 10.1097/MS9.0000000000004126. eCollection 2025 Dec. No abstract available. PMID 41377326
• Pattar GR, Wirta D, Jerkins G, Paauw J, McLaurin EB, Liu A, Evans DG, Kenyon K, Cline N, Gupta PK, Meng I, Senchyna M; COMET-2 and COMET-3 Study Groups. Acoltremon Ophthalmic Solution 0.003% for Signs and Symptoms of Dry Eye Disease: Results of Phase 3 Pivotal COMET-2 and COMET-3 Studies. Ophthalmology. 2026 May;133(5):563-574. doi: 10.1016/j.ophtha.2025.09.018. Epub 2025 Sep 30. PMID 41038456
• Lee A. Acoltremon: First Approval. Drugs. 2025 Oct;85(10):1307-1310. doi: 10.1007/s40265-025-02218-5. Epub 2025 Jul 30. PMID 40736647
• Zhou Y, Zhang W, Sun F. Acoltremon: The first TRPM8 agonist approved for the treatment of dry eye disease. Drug Discov Ther. 2025 Jul 4;19(3):210-211. doi: 10.5582/ddt.2025.01048. Epub 2025 Jun 27. PMID 40571589
• Methods of Reducing Corneal Endothelial Cell Loss U.S. Patent Application, PCT/US2014/066551, filed November 20, 2014 Developed novel methodology to assess decreased nerve density in patients at risk for endothelial cell loss and preventing endothelial cell loss through neuropeptide based therapies.

Identifiers

NCT: NCT07502378 · Study009655 · RTI #25-RX23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗