Clinically Relevant Activity of the Novel RASP Inhibitor Reproxalap in Allergic Conjunctivitis: The Phase 3 ALLEVIATE Trial

PURPOSE: To assess the post-acute activity and clini-cal utility of reproxalap, a novel reactive aldehyde species (RASP) inhibitor, versus vehicle in patients with sea-sonal allergic conjunctivitis. DESIGN: Parallel-group, double-masked, randomized Phase 3 trial. METHODS: Two topical ocular reproxalap concentra-tions (0.25% and 0.5%) were evaluated versus vehicle in patients with allergic conjunctivitis randomized 1:1:1 and treated with test article 10 minutes prior to conjuncti-val seasonal allergen challenge. The primary endpoint was area under the post-acute ocular itching score (range = 04) curve from 10 to 60 minutes after challenge. The key secondary endpoint was the proportion of subjects with =2 points improvement from their peak ocular itching score at baseline. RESULTS: A total of 318 patients were randomized at 11 US sites. Both concentrations of reproxalap (0.25% and 0.5%) achieved the primary endpoint (P <.0001 and P =.003, respectively) and the key secondary endpoint (P =.0005 and P =.02, respectively). Time to com-plete resolution of ocular itching was statistically faster for both reproxalap concentrations than for vehicle (P <.0001 and P =.001, respectively). No safety or tolerability concerns were noted. The most common adverse event was mild and transient instillation site irritation. CONCLUSION: Reproxalap was effective at reducing oc-ular itching in patients with allergic conjunctivitis. Re-proxalap activity was clinically relevant, as assessed by responder-based and distributional analyses. ALLEVI-ATE represents one of the first allergic conjunctivitis Phase 3 trials of a novel mechanism of action in decades, and is unique among conjunctival allergen challenge tri-als in assessing clinical relevance with standard and val-idated techniques. (Am J Ophthalmol 2021;230: 60-67. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/))