ALDX NEWS >>> Aldeyra Therapeutics Announces Phase 3 TRANQUILITY Dry Eye Disease Trial Design
February 04 2021
TRANQUILITY to Utilize Two-Day Treatment and Challenge Design
Consistent with Previously Announced Top-Line TRANQUILITY Run-In Cohort Results, Ocular Redness Selected as Primary Endpoint
Tear RASP Levels Reduced After Single Doses of Reproxalap in Run-In Cohort of TRANQUILITY and Selected as Secondary Endpoint for Confirmation of Mechanism of Action
Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a clinical-stage biotechnology company focused on the development of novel therapies with the potential to improve the lives of patients with immune-mediated diseases, today announced the finalization of the design of the Phase 3 TRANQUILITY Trial of 0.25% reproxalap ophthalmic solution for the treatment of dry eye disease. Consistent with previously announced results from the run-in cohort of TRANQUILITY, ocular redness over 90 minutes in a dry eye chamber will be the primary endpoint. Approximately 150 dry eye disease patients are expected to be enrolled per arm. The TRANQUILITY protocol will utilize the two-day dosing paradigm, dry eye challenge design, and enrollment criteria of the run-in cohort.
Tear RASP levels from the TRANQUILITY run-in cohort were reduced after single doses of the novel RASP inhibitor reproxalap, as assessed by enzyme-linked immunosorbent assay (ELISA) of 4-hydroxynonenal protein adducts (HNE), a RASP selected based on results from a natural history study of dry eye patients conducted by Aldeyra. For subjects with sufficient tear volumes for analysis, across the two doses where tear RASP levels were assessed before and after drug administration, HNE levels declined by an average of 1018 picograms/milliliter (pg/mL) in reproxalap-treated patients (n=9) versus an increase of 32 pg/mL in vehicle-treated patients (n=7). Accordingly, tear RASP levels have been selected as a secondary endpoint for confirmation of mechanism of action. HNE is well-characterized in the scientific literature as a critical pro-inflammatory RASP,1 and ocular levels of HNE correlate with the signs and symptoms of dry eye disease.2
“The rapid activity of reproxalap demonstrated in the run-in cohort of TRANQUILITY in improving ocular redness, potentially the only dry eye disease sign of interest to patients, allows for the use of a two-day challenge design — a time and cost-efficient model for Phase 3 clinical testing,” stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra. “Consistent with the observed rapid improvement in dry eye disease signs and symptoms, the reduction of tear RASP levels was evident after single doses of reproxalap, representing, to our knowledge, the first confirmation of drug mechanism in clinical trials of a topical ocular dry eye disease drug.”
TRANQUILITY and the confirmatory Phase 3 TRANQUILITY-2 Trial are expected to initiate in the first half of 2021. Results from both trials are expected in the second half of 2021.
