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

Abstract

PURPOSE:

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.

DESIGN:

Parallel-group, double-masked, randomized Phase 3 trial.

METHODS:

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.

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 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.

CONCLUSION:

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.

• Authors: David Clark, Bill Cavanagh, Alan L Shields, Paul Karpecki, John Sheppard, Todd C Brady
• Journal: American journal of ophthalmology (Am J Ophthalmol) Vol. 230 Pg. 60-67 (10 2021) ISSN: 1879-1891 [Electronic] United States
• PMID: 33945820 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Aldehydes
• Allergens
• Aminoquinolines
• Anti-Allergic Agents
• Ophthalmic Solutions
• reproxalap

Topics

• Aldehydes (therapeutic use)
• Allergens (therapeutic use)
• Aminoquinolines (therapeutic use)
• Anti-Allergic Agents (therapeutic use)
• Conjunctivitis, Allergic (diagnosis, drug therapy)
• Double-Blind Method
• Humans
• Ophthalmic Solutions (therapeutic use)