A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% in the Treatment of Dry Eye Disease

Abstract Objective Evaluate the safety and efficacy of OTX-101, a novel aqueous nanomicellar formulation of cyclosporine (0.09%), in the treatment of subjects with dry eye disease (DED). Design A randomized, multicenter, vehicle-controlled, double-masked, phase 3 clinical trial. Participants Adults (18–90 years of age) with a history and clinical diagnosis of DED, a global symptom score ≥40 (0–100 range), and a lissamine green conjunctival staining score of ≥3 and ≤9 (0–12 range) in at least 1 eye. Methods Eligible subjects entered a run-in period of 14–20 days, in which all subjects administered vehicle twice daily. Subjects that remained eligible at the baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment with OTX-101 0.09% or vehicle for 84 days. Main Outcome Measures Efficacy assessments included signs (unanesthetized Schirmer tear test, corneal and conjunctival staining) and symptoms (global symptom score) of DED. The primary endpoint was the proportion of eyes with a clinically meaningful improvement (increase of ≥10 mm) in Schirmer test score at day 84. Safety evaluations included adverse events (AE), visual acuity, and intraocular pressure monitoring, as well as slit-lamp and dilated ophthalmoscopy/fundus examinations. Results A total of 744 subjects were randomized and received study medication (371 to OTX-101 0.09% and 373 to vehicle). The primary endpoint was achieved; a significantly greater percentage of eyes in the OTX-101 0.09% treatment group experienced an increase of ≥ 10 mm in the Schirmer test score at day 84 (OTX-101 0.09%: 16.6%; vehicle: 9.2%; P Conclusions Clinically and statistically significant improvements in tear production and ocular surface integrity were observed in subjects treated with OTX-101 0.09% for DED. The safety and efficacy results support the continued development of OTX-101 as a treatment for DED.