A Randomized Double-Masked Phase 2a Trial to Evaluate Activity and Safety of Topical Ocular Reproxalap, a Novel RASP Inhibitor, in Dry Eye Disease

J Ocul Pharmacol Ther. 2021 May;37(4):193-199. doi: 10.1089/jop.2020.0087. Epub 2021 Jan 15.


Purpose: To determine whether reproxalap, a novel reactive aldehyde species (RASP) inhibitor, is safe and effective for the treatment of the signs and symptoms of dry eye disease (DED). Methods: In a randomized double-masked parallel-group Phase 2a trial of 3 topical ocular reproxalap formulations (0.1% ophthalmic solution, 0.5% ophthalmic solution, and 0.5% lipid ophthalmic solution), 51 patients with DED were randomly assigned 1:1:1 at a single US site. Eyes were treated bilaterally 4 times daily for 28 days, and standard DED signs and symptoms were assessed at baseline and after 7 and 28 days of dosing. Tear RASP levels were assessed at baseline and at day 28. Results: The effect of treatment on DED signs and symptoms was similar across the treatment arms, and pooled data from the 28-day treatment period demonstrated significant improvement from baseline in Symptom Assessment in Dry Eye Disease score (P = 0.003), Ocular Discomfort Scale score (P < 0.0001), Ocular Discomfort Score and 4-Symptom Questionnaire overall score (P = 0.0004), Schirmer's test (P = 0.008), tear osmolarity (P = 0.003), and lissamine green total staining score (P = 0.002). Improvements in DED symptoms were evident within 1 week of therapy, and effect sizes generally approached or exceeded 0.5. No significant changes in safety measures were observed. Conclusion: The results suggest that the novel RASP inhibitor reproxalap has the potential to mitigate the signs and symptoms of DED, and may represent a new, rapidly and broadly active treatment approach for DED (NCT03162783).

Keywords: RASP inhibitor; dry eye disease; inflammation; reproxalap.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / antagonists & inhibitors*
  • Administration, Topical
  • Aged
  • Aminoquinolines / administration & dosage
  • Aminoquinolines / adverse effects
  • Aminoquinolines / therapeutic use*
  • Dry Eye Syndromes / drug therapy*
  • Female
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Middle Aged
  • Ophthalmic Solutions / administration & dosage*
  • Safety
  • Treatment Outcome


  • Acute-Phase Proteins
  • Aminoquinolines
  • Ophthalmic Solutions
  • rheumatoid arthritis specific protein, human
  • reproxalap

Associated data

  • ClinicalTrials.gov/NCT03162783