Early Onset and Broad Activity of Reproxalap in a Randomized, Double-Masked, Vehicle-Controlled Phase 2b Trial in Dry Eye Disease.

Abstract

To assess the activity of reproxalap, a novel reactive aldehyde species (RASP) inhibitor, relative to vehicle in patients with dry eye disease (DED) DESIGN: Randomized, double-masked, vehicle-controlled Phase 2b trial METHODS: Three hundred patients with DED were randomly assigned 1:1:1 at multiple US sites to receive 0.1% topical ocular reproxalap, 0.25% topical ocular reproxalap, or vehicle. Eyes were treated bilaterally 4 times daily for 12 weeks. Standard signs and symptoms of DED were assessed at baseline and at Weeks 2, 4, 8, and 12. A dose response was observed for signs and symptoms of DED. Relative to vehicle over 12 weeks of therapy, the largest symptomatic improvement was observed in ocular dryness (0.25%, P = .047), and the largest objective sign improvement was observed in nasal region fluorescein staining (0.25%, P = .030). A greater proportion of patients receiving 0.25% reproxalap vs. vehicle reported dryness scores of 0 (P = .012). Improvements in combined DED symptoms were evident by the first post-baseline visit (Week 2, 0.25%, P < .0001) in patients with baseline scores greater than or equal to median values. No significant changes in safety measures were observed. The novel RASP inhibitor reproxalap demonstrated rapid, broad, and clinically relevant symptomatic control, in conjunction with statistically significant improvement over vehicle in signs of DED as demonstrated by fluorescein staining, in DED patients over 12 weeks of therapy. The results represent the first vehicle-controlled evidence for the therapeutic potential of RASP inhibition to mitigate the signs and symptoms of dry eye disease.