Aldeyra Therapeutics announced expanded results from the company’s allergen chamber clinical methods trial of topical ocular reproxalap in patients with allergic conjunctivitis, and phase 3 clinical trial plans based on recent feedback from the FDA.
“The expanded results from our allergen chamber trial demonstrate highly statistically significant activity of reproxalap relative to vehicle across all assessed symptoms and signs,” Todd C. Brady, MD, PhD, President and CEO of Aldeyra, said in a company news release. “Based on the positive outcome of the trial, we have reached agreement with the FDA on the design and the primary endpoint for our Phase 3 INVIGORATE trial – statistical significance in ocular itching at a majority of time points over a pre-specified range. Importantly, in the completed allergen chamber trial, all time points to be pre-specified in the INVIGORATE trial were statistically significant.”
The double-masked, randomized, vehicle-controlled, crossover allergen chamber clinical methods trial assessed the efficacy and safety of 0.25% and 0.5% concentrations of reproxalap topical ophthalmic solution compared with vehicle in 70 patients with ocular allergy to ragweed. Patient-reported ocular itching and tearing, and investigator-assessed ocular redness, were recorded at various intervals over approximately 3.5 hours during exposure to a standardized amount of ragweed pollen. Test article was administered before chamber entry and at 90 minutes post-entry, near the peak of allergy symptoms and signs.
Relative to patients treated with vehicle, patients treated with 0.25% or 0.5% reproxalap demonstrated statistically significant reduction in ocular itching (P<0.0001), redness (P<0.0001), and tearing (P<0.0001). The total ocular symptom score, a combination of itching, redness, and tearing, was also significantly lower in reproxalap-treated subjects than in vehicle-treated subjects (P<0.0001 for both concentrations). Consistent with the positive results from the ALLEVIATE phase 3 clinical trial in allergic conjunctivitis released earlier this year, there was no statistical difference between the activity of 0.25% and 0.5% reproxalap. Consistent with all prior clinical experience with topical ocular reproxalap in over 1,000 patients across 12 clinical trials, there were no observed safety or tolerability concerns, and the most common treatment-emergent adverse event was transient instillation site irritation.
“We believe that the allergic conjunctivitis results released today, in aggregate, represent the first rigorous demonstration of activity of a late-stage, novel immune-modulating agent in an allergen chamber,” David J. Clark, MD, MRCP, Chief Medical Officer of Aldeyra, said in the news release. “The allergen chamber is an innovative and demanding assessment that combines real-world applicability with controlled allergen exposure. The results from the trial indicated distinct prophylactic and treatment activity of reproxalap in reducing all of the primary signs and symptoms of allergic conjunctivitis: ocular itching, redness, and tearing.”
The phase 3 INVIGORATE trial, which is expected to initiate in the first half of 2020, will evaluate 0.25% reproxalap versus vehicle in an allergen chamber. The primary endpoint will be achieved if statistically significant reduction in ocular itching between drug and vehicle is demonstrated at the majority of eleven time points in a pre-specified range from 110 to 210 minutes following chamber entry. In the completed allergen chamber trial, reproxalap was statistically superior to vehicle at every time point to be pre-specified in INVIGORATE.