Phase 3 Randomized Clinical Trial Evaluating the Safety of Reproxalap in Patients With Dry Eye Disease.

INTRODUCTION

Reactive aldehyde species (RASP) are proinflammatory molecules that have been implicated in ocular inflammatory diseases, including dry eye disease (DED). Reproxalap is a small molecule RASP inhibitor in development for the treatment of DED. The objective of this clinical trial was to evaluate the long-term safety of reproxalap 0.25% ophthalmic solution compared with vehicle in patients with DED.

METHODS

This was a phase 3, multicenter, double-masked, randomized, vehicle-controlled, parallel-group safety clinical trial in patients with DED. Eligible patients were randomized 2:1 to bilateral treatment with reproxalap or vehicle for 6 weeks or 12 months, with the treatment administered four times daily (QID) for the first 4 weeks then twice daily (BID) for either 2 weeks or 11 months. Safety assessments included treatment-emergent adverse events (TEAEs), slit-lamp biomicroscopy, dilated fundoscopy, best-corrected visual acuity (BCVA), intraocular pressure, corneal endothelial cell density, and laboratory assessments. The primary endpoint was the occurrence of treatment-related serious ocular TEAEs.

RESULTS

A total of 757 patients were enrolled and treated with reproxalap (n = 504) or vehicle (n = 253). In the 12-month arms, 111 and 72 patients receiving reproxalap and vehicle, respectively, completed the trial. There were no treatment-related serious TEAEs. The most common TEAE in reproxalap-treated patients was transient, mild, instillation site irritation, most commonly lasting < 1 min. Other ocular TEAEs were similar between reproxalap and vehicle. No safety concerns were identified. Post hoc analysis of BCVA change from baseline in the 12-month safety population showed larger BCVA improvement over 12 months with reproxalap compared with vehicle (p = 0.0185).

CONCLUSIONS

The results support the safety of long-term topical reproxalap therapy in patients with DED.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04735393.