Phase 3 Efficacy (Worse-Eye Analysis) and Long-Term Safety Evaluation of OTX-101 in Patients with Keratoconjunctivitis Sicca

BACKGROUND: OTX-101 is approved for treatment of keratoconjunctivitis sicca (KCS). We present results of a phase 3 worse-eye efficacy analysis and 1-year safety extension. METHODS: During the double-masked treatment phase, patients with bilateral KCS were randomized 1:1 to 12 weeks OTX-101 or vehicle 1 drop per eye twice daily. Efficacy assessments included Schirmer’s test and corneal and conjunctival staining. All patients who completed the treatment phase were eligible for enrollment in the open-label extension and received 1 drop OTX-101 twice daily for up to 52 weeks. Safety endpoints included adverse event (AE) monitoring, Snellen visual acuity (VA), intraocular pressure (IOP), slit-lamp examination (SLE), and dilated fundoscopy. RESULTS: Overall, 745 and 258 patients enrolled in the treatment and safety extension phases, respectively. At 12 weeks, number (%) of patients with Schirmer’s score increase of ≥10 mm from baseline was 76 (20.5%) vs. 42 (11.3%) for OTX-101 vs. vehicle (P=0.0005). OTX-101 significantly improved total conjunctival staining vs. vehicle at week 12 (least squares mean change from baseline −1.65 [0.12] vs. −1.12 [0.12], P=0.0013), and number (%) of patients with clear central corneas vs. vehicle at week 12 (222 [64.0%] vs. 199 [55.3%], P=0.0179). In the 1-year safety extension, AEs were mostly mild; instillation site pain was most common in 59 (22.9%) patients (17 [13.2%] vs. 42 [32.6%] patients receiving prior OTX-101 and vehicle). No safety concerns were raised by VA, IOP, SLE, and fundoscopy. CONCLUSION: OTX-101 efficacy was confirmed in the eye with lower baseline Schirmer’s score. OTX-101 was well tolerated long term. CLINICAL TRIAL: Registered at ClinicalTrials.gov on July 27, 2016. NCT02845674 https://clinicaltrials.gov/ct2/show/NCT02845674?term=OTX-101&draw=2&rank=1.