Clinical Ophthalmology (Dec 2023)
The Phase 3 INVIGORATE Trial of Reproxalap in Patients with Seasonal Allergic Conjunctivitis
Abstract
Christopher E Starr,1 Kelly K Nichols,2 Jacob R Lang,3 Todd C Brady4 1Department of Ophthalmology, Weill Cornell Medicine, New York, NY, USA; 2School of Optometry, University of Alabama, Birmingham, AL, USA; 3College of Optometry, the Ohio State University, Columbus, OH, USA; 4Aldeyra Therapeutics, Lexington, MA, USACorrespondence: Todd C Brady, Aldeyra Therapeutics, 131 Hartwell Avenue, Suite 320, Lexington, MA, 02421, USA, Email [email protected]: There is an unmet need for new treatments for allergic conjunctivitis.Objective: To assess the activity of reproxalap, a novel reactive aldehyde species modulator, in a real-world model of seasonal allergen exposure.Methods: The INVIGORATE Trial, a prospective, quadruple-masked, vehicle-controlled, crossover, sequence-randomized Phase 3 trial, tested the efficacy of reproxalap in adults with a history of moderate to severe allergic conjunctivitis, ragweed pollen allergy, and allergen chamber-induced ocular itching and redness. Patients were randomly assigned (1:1) to receive 0.25% reproxalap ophthalmic solution or vehicle, followed by a 2-week washout period before crossing over to the other test article. The primary endpoint was ocular itching from 110 to 210 minutes after chamber entry; the key secondary endpoint was ocular redness over the chamber duration (0– 4 scales for both endpoints).Results: Of the 95 randomly assigned patients, 89 completed all visits (reproxalap to vehicle: n = 46; vehicle to reproxalap: n = 43). Primary and key secondary endpoints were met: reproxalap significantly reduced ocular itching (mean [SE]: − 0.50 [0.03], p < 0.001) and redness (− 0.14 [0.01], p < 0.001) relative to vehicle. Responder analyses confirmed the clinical relevance of both end points. Reproxalap was safe and well tolerated. No clinically significant changes in safety assessments were observed. No serious or severe treatment-emergent adverse events (TEAEs) were reported. The most commonly reported TEAE was mild and transient installation site irritation after reproxalap versus vehicle administration.Conclusion: In this well-controlled allergen chamber trial, reproxalap was statistically superior to vehicle across typical symptoms and signs of allergic conjunctivitis.Trial Registration: NCT04207736.Keywords: allergic conjunctivitis, reactive aldehyde species, reproxalap, ocular itching, ocular redness
