Safety and effcacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye

Abstract

Purpose: To evaluate the safety and effcacy of ophthalmic MIM-D3, a tyrosine kinase Trk receptor agonist, in patients with dry eye. Design: A prospective, two-center, randomized, double-masked, placebo-controlled Phase study. Methods: A total of 150 dry eye patients were randomized 1:1:1 to study medicatio (1% MIM-D3, 5% MIM-D3, or placebo) and dosed twice daily (BID) for 28 days. Key eligibilit criteria included exacerbation in corneal staining and ocular discomfort in the Controlle Adverse Environment (CAESM) on two visits, separated by 1 week of BID dosing with artifci tears. Safety and effcacy were evaluated at baseline, throughout treatment, and for 2 week post-treatment. The pre-specifed primary outcome measures were fuorescein corneal stainin post-CAE at day 28 and diary worst symptom scores over 28 days. Secondary outcomes include the pre-, post-, and the change from pre- to post-CAE fuorescein and lissamine green stainin in both corneal and conjunctival regions, as well as individual diary symptoms. Results: The prespecifed primary endpoints were not met. Compared with placebo, fu rescein corneal staining at day 28 was signifcantly improved (P, 0.05) in the 1% MIM D3 group for the assessment of change from pre-CAE to post-CAE. In addition, followin CAE exposure, patients in the 1% MIM-D3 group showed signifcant improvements versu placebo (P, 0.05) in inferior fuorescein and lissamine green staining after 14 and 28 day Compared with placebo, patients in the 5% MIM-D3 group reported signifcantly lower dai diary scores for ocular dryness (P, 0.05). In a subgroup defned by higher symptom scor during the run-in period, signifcant treatment effects (P, 0.05) were observed for diar symptoms for both MIM-D3 doses. Ocular adverse events were mild and not considered t be treatment-related. Conclusion: Treatment with topical ophthalmic MIM-D3 demonstrated protection against th effects of a CAE challenge on dry eye signs, reduced patient-reported diary symptoms, with favorable safety profle. © 2013 Meerovitch et al.