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

•There is a need for new non-histaminic therapies for allergic conjunctivitis•Reproxalap is a topical reactive aldehyde species (RASP) inhibitor that has demonstrated activity for allergic conjunctivitis•In this Phase 3 trial, reproxalap was well tolerated and effective for treating allergic conjunctivitis•This allergic conjunctivitis challenge model assessed clinical relevance with validated techniques To assess the post-acute activity and clinical utility of reproxalap, a novel reactive aldehyde species (RASP) inhibitor, versus vehicle in patients with seasonal allergic conjunctivitis. Parallel-group, double-masked, randomized Phase 3 trial. Two topical ocular reproxalap concentrations (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 conjunctival seasonal allergen challenge. The primary endpoint was area under the post-acute ocular itching score (range = 0-4) 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. 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 complete 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. Reproxalap was effective at reducing ocular itching in patients with allergic conjunctivitis. Reproxalap activity was clinically relevant, as assessed by responder-based and distributional analyses. ALLEVIATE 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 trials in assessing clinical relevance with standard and validated techniques. There is a need for new non-histaminic therapies for the treatment of allergic conjunctivitis. This parallel-group, double-masked, randomized Phase 3 trial assessed the post-acute activity and clinical utility of reproxalap, a novel reactive aldehyde species inhibitor, versus vehicle in patients with seasonal allergic conjunctivitis. Reproxalap demo