Abstract
Purpose :
Reproxalap is a novel reactive aldehyde species (RASP) sequestering agent representing a new anti-inflammatory drug class in late-stage development for the treatment of dry eye disease (DED), as well as noninfectious anterior uveitis and allergic conjunctivitis. A controlled Phase 2b clinical trial was conducted to confirm endpoint and dose selection for a Phase 3 DED program.
Methods :
In a multi-center, randomized, double-masked, parallel-group, vehicle-controlled trial of reproxalap ophthalmic solution (0.25% and 0.1%), 300 subjects with DED were randomized (1:1:1) to receive either reproxalap (0.25%), reproxalap (0.1%), or vehicle ophthalmic solution bilaterally four times daily (QID) for 12 weeks. DED symptoms and signs were assessed at baseline, then at 2, 4, 8, and 12 weeks of dosing.
Results :
Both reproxalap groups demonstrated activity through Week 12. The reproxalap 0.25% group was statistically superior to vehicle in improvement from baseline in overall ocular discomfort (p<0.05), dryness (p<0.05), and stinging (p<0.05), as measured by the Ora Calibra® Ocular Discomfort and 4 Symptom Questionnaire (OD4SQ). In subjects with baseline dryness symptom scores equal to or above the median, improvement in the 0.25% group was statistically superior to vehicle at Weeks 2 and 12. Statistically significant differences in change from baseline favoring reproxalap 0.1% over vehicle were observed in fluorescein nasal region staining at Week 12, and with reproxalap 0.25% over vehicle at Week 8 as measured by the Ora Calibra® Corneal and Conjunctival Staining Scale. Improvement in the 0.25% group was statistically superior to that of the vehicle group at Weeks 2, 8 and 12 in patients with nasal fluroescein staining scores at or above the median. Generalized estimating equation responder analyses demonstrated statistical superiority of the reproxalap 0.25% versus vehicle as soon as Week 2. Across most analyses, a dose-response was observed.
Conclusions :
The novel mechanism RASP inhibitor reproxalap was statistically superior to vehicle across multiple DED symptoms and signs. Consistent with a prior Phase 2a clinical trial, improvements in symptoms and signs were observed as early as two weeks of treatment. Reproxalap 0.25% will be advanced to a Phase 3 program in DED.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.