The clinical trial involved 158 patients, with 80 being randomly assigned to receive 0.25% reproxalap ophthalmic solution and 78 being randomly assigned to receive vehicle ophthalmic solution.
Patients were given four doses one day before and two doses during a 90-minute dry eye chamber with low humidity, high airflow, and forced visual tasking.
The phase 2 trial has more than 90% power to detect statistical significance in the primary endpoint of ocular redness throughout all time points in the dry eye chamber, based on final enrollment and data from the run-in cohort of TRANQUILITY, Aldeyra's ongoing phase 3 trial in dry eye disease.
The reproxalap group's ocular redness scores were statistically lower than the vehicle group's (P=0.016). Furthermore, after the first dosage, Schirmer's test scores were directionally in favor of reproxalap over vehicle and neared statistical significance (P=0.068).
At all of the 18 time points when symptoms were assessed in the dry eye chamber, including the first time point in the chamber, reproxalap-treated subjects had lower mean visual analog scale ocular dryness and ocular discomfort scores than vehicle-treated subjects, though the differences were not statistically significant.
The trial's tear RASP level data should be released later this quarter.
There were no apparent safety or tolerability problems in the trial, which is consistent with the clinical experience of reproxalap in over 1,300 patients.
The most common adverse event was mild and transient instillation site discomfort lasting less than 1 minute and similar to many prescribed topical ophthalmic medications for anterior segment inflammation.
“Complementing our rapid and durable symptom control evidenced in three 12-week clinical trials, we are excited to announce achievement of statistical significance of an objective sign of dry eye disease in a well-controlled clinical trial,” Todd C. Brady, MD, PhD, President and Chief Executive Officer of Aldeyra, said in a company news release.
“Ocular redness may be the only dry eye disease sign that is of importance to patients, and the reduction in redness observed in this trial following reproxalap treatment potentially represents a major advance for the chronic treatment of dry eye disease.”
TRANQUILITY and TRANQUILITY-2 are two phase 3 clinical trials of reproxalap in patients with dry eye condition. Each trial is expected to enroll 300 patients, with ocular redness as the primary endpoint.
Data from the TRANQUILITY trials are scheduled to be provided before the end of the year, pending confirmation of statistical powering and other analyses of the phase 2 clinical trial results announced today.
Reproxalap, an investigational new drug, is a novel small-molecule immune-modulating covalent inhibitor of RASP (reactive aldehyde species), which are elevated in ocular and systemic inflammatory disease.
Reproxalap’s mechanism of action has been validated with the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications.
Reproxalap is a 0.25 percent ophthalmic solution now in phase 3 clinical research for the treatment of dry eye disease and allergic conjunctivitis, two ocular inflammatory conditions that frequently occur together.