Effect of Reproxalap Treatment on Dry Eye Disease Symptoms: Analysis of Pooled Data From Two Randomized, Vehicle-Controlled, 12-Week Clinical Trials

Reproxalap is a novel reactive aldehyde species inhibitor. Pooled data from two clinical trials were used to evaluate effects on symptoms and safety of reproxalap treatment versus vehicle in participants with dry eye disease (DED). Data were pooled from identically designed arms of two 12-week, randomized, vehicle-controlled, double-masked, parallel-group clinical trials comparing topical ophthalmic reproxalap 0.25% with vehicle, each dosed four times daily for 4 weeks then twice daily for 8 weeks, in participants with DED. Symptoms of ocular dryness and ocular discomfort were assessed using a visual analog scale (0–100) in the intent-to-treat ocular dryness (ITTOD) population (prespecified for the symptom primary endpoint analysis in each trial) of participants with a baseline ocular dryness score of ≥ 3 on the Ora Calibra ® Ocular Discomfort & 4-Symptom Questionnaire. Safety parameters were evaluated in all treated participants. A total of 417 participants received study treatment (207 reproxalap, 210 vehicle), and 335 participants were included in the ITTOD population (167 reproxalap, 168 vehicle). The mean improvement from baseline in both ocular dryness and ocular discomfort scores was greater with reproxalap than vehicle at each timepoint (nominal p < 0.05). The least-squares mean difference (reproxalap − vehicle) in overall change from baseline from week 1 to week 12 was −8.5 (95% CI −12.6 to −4.5, p < 0.001) for ocular dryness score and −7.7 (95% CI −11.8 to −3.5, p < 0.001) for ocular discomfort score. The most common adverse event was mild instillation site irritation. There were no serious treatment-related adverse events. Reproxalap reduced ocular dryness and discomfort symptoms compared with vehicle as soon as week 1, the first post-baseline assessment, and there were no safety concerns. Reproxalap may represent an innovative, rapidly acting therapeutic option for patients with DED. Clinicaltrials.gov NCT03916042 and NCT03879863.