Effect of OTX-101, a Novel Nanomicellar Formulation of Cyclosporine A, on Corneal Staining in Patients With Keratoconjunctivitis Sicca: A Pooled Analysis of Phase 2b/3 and Phase 3 Studies

Abstract

Background: Keratoconjunctivitis sicca affects 5% to 33% of the population and is often accompanied by symptoms such as burning and dryness. This pooled analysis evaluated total and central corneal fluorescein staining (CFS) in patients receiving OTX-101 0.09% or vehicle in phase 2b/3 and 3 studies and whether improvements in corneal staining correlated with improved visual acuity.

Methods: In these randomized, vehicle-controlled studies, patients received 1 drop of OTX-101 or vehicle in both eyes twice daily. Corneal staining was performed at baseline and days 28, 56, and 84. CFS was evaluated in each zone (0-to-4 scale); total corneal staining (0-to-20 scale per eye) was averaged over both eyes. Pooled safety assessments included adverse event monitoring.

Results: Mean baseline CFS total scores (SD) were 4.2 (2.5) and 4.3 (2.6) for the OTX-101 (n = 523) and vehicle (n = 525) groups, respectively. For total corneal staining, least squares mean changes from baseline (standard error) were -0.9 (0.08) versus -0.5 (0.08) for OTX-101 and vehicle, respectively (P = 0.0008), on day 28 and -1.4 (0.09) versus -0.9 (0.09) on day 84 (P = 0.0002). There was a significantly high correlation (P = 0.0117) between reduced central corneal staining and improved visual acuity on day 84. Treatment-related adverse events were mostly mild, with instillation site pain reported by 21.8% and 4.0% of patients receiving OTX-101 and vehicle, respectively.

Conclusions: Treatment with OTX-101 led to greater improvements versus vehicle in corneal surface staining as early as 4 weeks, and further improvements were seen up to 12 weeks. OTX-101 was well tolerated in patients with keratoconjunctivitis sicca.

FIGURE 1.

Patient disposition. Patients who received OTX-101 0.05% only in the phase 2b/3 study are not included in the present pooled analysis.

FIGURE 2.

Least squares mean change from baseline on days 28, 56, and 84 in corneal fluorescein staining in patients treated with OTX-101 versus vehicle in the pooled population for (A) total score, (B) central zone, (C) inferior zone, (D) lateral zone, (E) medial zone, and (F) superior zone. P values for OTX-101 0.09% versus vehicle.

FIGURE 3.

Mean central corneal staining score over time in patients with baseline scores >0. P values for OTX-101 least squares mean change from baseline versus vehicle.

FIGURE 4.

Correlation between (A) central corneal staining and (B) Snellen VA. P values for OTX-101 0.09% versus vehicle.