Clinical Ophthalmology (Jan 2021)
Phase 3 Efficacy (Worse-Eye Analysis) and Long-Term Safety Evaluation of OTX-101 in Patients with Keratoconjunctivitis Sicca
Abstract
John Sheppard,1 Mark Bergmann,2 Barry A Schechter,3 Jodi Luchs,4 Abayomi Ogundele,5 Paul Karpecki6 1Virginia Eye Consultants, Norfolk, VA, USA; 2Apex Eye, Cincinnati, OH, USA; 3Florida Eye Microsurgical Institute, Boynton Beach, FL, USA; 4Florida Vision Institute, West Palm Beach, FL, USA; 5Medical Affairs, Sun Pharmaceutical Industries, Inc, Princeton, NJ, USA; 6Kentucky Eye Institute, Lexington, KY, USACorrespondence: John SheppardVirginia Eye Consultants, Suite #210, 241 Corporate Blvd, Norfolk, VA 23502, USATel +1 757 226-8021Email [email protected]: 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.Keywords: cyclosporine A, dry-eye disease, keratoconjunctivitis sicca; KCS, OTX-101
