Reproxalap Improves Signs and Symptoms of Allergic Conjunctivitis in an Allergen Chamber: A Real-World Model of Allergen Exposure

Abstract

Purpose: To assess the prophylactic and treatment activity of reproxalap, a novel reactive aldehyde species inhibitor, in a real-world model of allergen exposure.

Methods: In a randomized, double-masked, vehicle-controlled, crossover Phase 2 trial, 70 adult patients with ≥2 years of moderate to severe allergic conjunctivitis history, a positive skin test to ragweed pollen, and allergen chamber-induced ocular itching and redness scores of ≥2.5 and ≥2 (both scales range from 0 to 4), respectively, were randomized 1:1:1 to one of three sequences: 0.25% reproxalap, 0.5% reproxalap, and placebo; 0.5% reproxalap, placebo, and 0.25% reproxalap; or placebo, 0.25% reproxalap, and 0.5% reproxalap. Symptoms and conjunctival redness were assessed over 3.5 hours in an allergen chamber of aerosolized ragweed pollen (3500 grains/m³). Test article was administered bilaterally just before chamber entry and at 90 minutes after chamber entry.

Results: Reproxalap was safe and well tolerated; 66 of 70 enrolled patients completed all visits. Relative to vehicle, both concentrations of reproxalap demonstrated statistically significant and clinically relevant improvements in ocular itching, tearing, and redness over the duration of exposure in the chamber (P < 0.001 for all assessments). Prophylactic and treatment activity of drug were demonstrated.

Conclusion: In an allergen chamber, reproxalap, a novel reactive aldehyde species inhibitor, was statistically superior to vehicle across the typical symptoms and signs of allergic conjunctivitis. These data are among the first rigorous clinical results demonstrating drug improvement in allergic conjunctivitis in an allergen chamber, a real-world model of allergen exposure.

Keywords: RASP inhibitor; allergen chamber; allergic conjunctivitis; inflammation; reproxalap.

Figure 1

Patient disposition. Sequence A = 0.25% reproxalap, 0.5% reproxalap, and vehicle; sequence B = 0.5% reproxalap, vehicle, and 0.25% reproxalap; sequence C = vehicle, 0.25% reproxalap, and 0.5% reproxalap.

Figure 2

Patient-reported ocular itching score. P values derived from mixed effect models for repeated measures analysis of change from baseline (just prior to chamber entry) over all time points in aggregate.

Figure 3

Patient-reported ocular tearing score. P values derived from mixed effect models for repeated measures analysis of change from baseline (just prior to chamber entry) over all time points in aggregate.

Figure 4

Investigator-assessed conjunctival redness score. P values derived from mixed effect models for repeated measures analysis of change from baseline (just prior to chamber entry) over all time points in aggregate.

Figure 5

Time to patient-reported ocular itching score of ≥2 for 0.25% reproxalap versus vehicle. P value derived from log-rank analysis.

Figure 6

Time to investigator-assessed conjunctival redness score of ≥2 for 0.25% reproxalap versus vehicle. P value derived from log-rank analysis.