The Safety and Biological Activity of OTT166, a Novel Topical Selective Integrin Inhibitor for the Treatment of Diabetic Eye Disease: A Phase 1b Study

Abstract

BACKGROUND AND OBJECTIVES: To evaluate the safety, tolerability, and biological activity of a topical selective integrin inhibitor (OTT166) eyedrop administered BID for diabetic retinopathy (DR) and diabetic macular edema (DME). STUDY DESIGN/MATERIALS AND METHODS: A prospective, multicenter, randomized, double-masked Phase 1b study. Subjects with nonproliferative DR and DME with central subfield thickness (CST) > 325 microns were randomized to OTT166 eyedrops (2.5% or 5%) BID for 28 days. Subjects were followed for an additional 28 days after treatment cessation. RESULTS: Forty-four subjects were enrolled. No drug-related serious adverse events (SAEs) and two drug-related adverse events (AEs) were reported. OTT166 was well-tolerated with no evidence of ocular toxicity. Best-corrected visual acuity (BCVA) remained stable. Mean central retinal thickness (CRT) overall was variable: +12.8/+1.8 microns at Day 28 (end of treatment) and -50.3/+5.5 microns at Day 56 (end of study) for the 2.5% and 5% groups, respectively. Median CRT overall demonstrated consistent reduction by end of study: -39.0/-16.5 microns for the 2.5% and 5% groups, respectively. Median responses were greater in the treatment-naïve group (-41.5/-26.0 microns for the 2.5% and 5% groups, respectively). Thirty-seven percent of ‘responder’ subjects exhibited a mean reduction in CRT of 46.6 microns on optical coherence tomography (OCT) at end of treatment (Day 28) which persisted to end of the study (Day 56) – mean reduction of 67.4 microns, suggesting a durable effect. CONCLUSION: OTT166 eyedrops were safe, well-tolerated, and demonstrated biological activity in 37% of responders. These results warrant further evaluation of OTT166 eyedrops.