Phase III RENEW Trial of ADX 102 meets primary objective in dry eye syndrome.- Aldeyra Therapeutics

Aldeyra Therapeutics announced positive top-line results from Part 1 of the adaptive Phase III RENEW Trial of topical ocular ADX 102 (reproxalap) in patients with dry eye disease. The RENEW Trial is an ongoing adaptive, two-part, multi-center, randomized, vehicle-controlled, double-masked, parallel-group Phase III trial of 0.25% topical ocular reproxalap compared to vehicle in patients with moderate to severe dry eye disease. The primary objective of RENEW Part 1 was to confirm dosing regimen, endpoints, and sample size for RENEW Part 2. In Part 1 of RENEW, 422 patients were randomized equally to receive either four-times-daily reproxalap or vehicle for twelve weeks (the constant dosing group) or four-times-daily reproxalap or vehicle for four weeks, followed by twice-daily reproxalap or vehicle for eight weeks (the induction-maintenance dosing group).

The primary objective of RENEW Part 1 was achieved. Observed activity versus vehicle of the induction-maintenance dosing regimen of topical ocular reproxalap was greater than that of the constant dosing group, and the induction-maintenance dosing regimen will be advanced to RENEW Part 2. The planned primary endpoints for RENEW Part 2 are ocular dryness score and fluorescein nasal region ocular staining score. RENEW Part 2 is expected to initiate in the first half of 2020 and enroll approximately 400 patients per arm at approximately 90% power to achieve statistical significance. In the induction-maintenance dosing group, the RENEW co-primary endpoint of patient-reported visual analog scale (VAS) ocular dryness from Weeks 2 to 12 was achieved (p=0.0004), and activity was observed as early as one week after initiation of therapy (p=0.001) and was maintained until the end of the trial. In the induction-maintenance dosing group from Weeks 2 to 12, reproxalap was statistically superior to vehicle in VAS ocular endpoints for itching (p=0.03), foreign body sensation (p=0.004), discomfort (p=0.003), photophobia (p=0.004), and pain (p=0.03).

In the induction-maintenance dosing group from Weeks 2 to 12, reproxalap was statistically superior to vehicle in Ocular Discomfort & 4-Symptom Questionnaire ocular endpoints for dryness (p=0.01), discomfort (p=0.03), burning (p=0.03), grittiness (p=0.003), and stinging (p=0.02). Although the improvement effect size of the co-primary endpoint of fluorescein nasal region ocular staining did not reach statistical significance, reproxalap was statistically superior to vehicle in reduction from baseline in the induction-maintenance dosing group from Weeks 1 to 4 of treatment (p=0.03), and statistical separation from vehicle was observed at Week 2 (p=0.04). Consistent with clinical experience in over 1,100 patients, no adverse findings on safety assessments were observed, and reproxalap was well-tolerated. The most common reported adverse event in reproxalap-treated patients was transient and mild instillation site irritation. Less than 8% of reproxalap-treated patients discontinued the trial due to adverse events, and moderate ocular adverse events were reported in fewer than 1% of subjects.