A novel reactive aldehyde species (RASP) inhibitor demonstrated rapid, broad, and clinically relevant symptomatic control and statistically significant improvement in signs and symptoms of dry eye disease (DED), according to trial results published in the American Journal of Ophthalmology. The phase 2b trial for reproxalap was the first vehicle-controlled trial for its treatment of DED.
The trial utilized 4 dry eye questionnaires as a measure of subjective symptoms and fluorescein staining as a measure of objective signs.
In the trial (NCT03404115), researchers randomly assigned 300 patients with a DED diagnosis with either reproxalap 0.1%, reproxalap 0.25%, or a vehicle. The patients received 1 drop in each eye 4 times daily for 12 weeks. At baseline and 12 weeks, the patients were exposed to a controlled adverse environment (CAE) of low humidity for 90 minutes. Signs and symptoms of DED were assessed at baseline and clinic visits at weeks 2, 4, 8, and 12.
Changes from baseline to 12 weeks for both reproxalap concentrations were numerically superior to the vehicle on all the subjective symptom scales used in the research. The 0.25% concentration was advanced to further clinical testing. Its largest symptomatic improvement, among all scales, was observed in ocular dryness (P =.047), and a greater proportion of patients receiving 0.25% reproxalap vs the vehicle reported dryness scores of 0 (P =.012).
The largest objective sign improvement was in nasal region fluorescein staining scores (P =.030). The improvement in combined DED symptoms was evident by week 2 (0.25%, P <.0001) in patients with baseline scores greater than or equal to median values.
The researchers report that 94% of patients in the 0.25% reproxalap group experienced adverse events compared with 31% of patients in the vehicle and 50% of patients in the 0.1% reproxalap group. In total, investigators noted 173 ocular treatment-emergent adverse events (TEAE); 102 of which involved ocular discomfort upon instillation. All TEAE were transient and self-limiting. The severity of ocular TEAE was rated as mild in 92.4% of cases. A total of 2 serious adverse events were observed; both were nonocular and deemed not related (angina pectoris, 0.25% reproxalap) or unlikely related (vertigo, 0.1% reproxalap) to the study drug.
Limitations of this study included the fact that the patients were not administered reproxalap the day of the CAE, and that the results consider only the most severe eye at baseline.
Disclosure: Financial support for this study was provided by Aldeyra Therapeutics, Inc. The study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.
Clark D, Tauber J, Sheppard J, Brady TC. Early onset and broad activity of reproxalap in a randomized, double-masked, vehicle-controlled phase 2b trial in dry eye disease. Am J Ophthalmol. Published online January 29, 2021. doi:10.1016/j.ajo.2021.01.011