Abstract
Purpose :
AG-80308 is a new chemical entity with a novel mechanism of action targeting the formyl peptide receptor pathway to resolve inflammation. This Phase 1b clinical study aims to evaluate the safety and efficacy of AG-80308 for the treatment of dry eye disease (DED).
Methods :
This was a multicenter, double-masked, randomized, parallel-group Phase 1b study evaluating the safety, tolerability, and dose-response of topical AG-80308 given twice daily for 3 months in patients with dry eye disease. 80 patients were planned to be enrolled and assigned 1:1:1:1 to receive 0.001%, 0.03%, and 0.1% AG-80308 in Formulation A or 0.03% AG-80308 in Formulation B. The efficacy measures included ocular surface staining (on a scale of 0-4), tear film breakup time, Schirmer’s test, meibomian gland assessments, and 7-item Visual Analogue Scale (VAS) for symptom assessments (0-100 scale).
Results :
AG-80308 showed clinically meaningful reductions in corneal and conjunctival staining, dry eye symptoms, and ocular surface disease index scores. Corneal staining was significantly improved from baseline with maximal reductions (mean ± SE) of -2.1 ± 0.57 by Day 43 (p=0.0001) and -2.7 ± 0.57 by Day 84 (p=0.0002). For eye discomfort, Formulation B 0.03% provided the best reduction of -14.1 ± 4.09 at Day 15 (p=0.02), -20.0 ± 5.57 at Day 43 (p=0.004) and -28.8 ± 6.29 at Day 84 (p=0.0004).
There was a dose-dependent increase in treatment emergent adverse events (TEAEs). The most common TEAE was mild to moderate eye discharge and crusting, both expected pharmacological effects of AG-80308. At the same dose, Formulation B showed a better safety profile than Formulation A with less discharge and crusting. No notable changes in any ocular safety assessment including BCVA and IOP were observed during this study. There were no servious adverse events in the study and no notable changes in hematology, serum chemistry, urinalysis, vital signs, or physical examination findings were observed.
Conclusions :
AG-80308 was proven safe when given BID for 3 months. AG-80308 has the potential to be a novel treatment for dry eye disease.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.