Safety and efficacy of MIM D3 ophthalmic solutions in a randomized placebo controlled Phase 2 clinical trial in patients with dry eye
Authors Meerovitch K, Torkildsen G, Lonsdale J, Goldfarb H, Lama T, Cumberlidge G, Ousler GW
Received 2 March 2013
Accepted for publication 13 April 2013
Published 26 June 2013 Volume 2013:7 Pages 1275—1285
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Karen Meerovitch,1 Gail Torkildsen,2 John Lonsdale,3 Heidi Goldfarb,4 Teresa Lama,1 Garth Cumberlidge,1 George W Ousler III5
1Mimetogen Pharmaceuticals Inc, Montreal, QC, Canada; 2Andover Eye Associates, Andover, MA, USA; 3Central Maine Eye Care, Lewiston, ME, USA; 4SDC, Tempe, AZ, USA; 5Ora Inc, Andover, MA, USA
Purpose: To evaluate the safety and efficacy of ophthalmic MIM-D3, a tyrosine kinase TrkA receptor agonist, in patients with dry eye.
Design: A prospective, two-center, randomized, double-masked, placebo-controlled Phase 2 study.
Methods: A total of 150 dry eye patients were randomized 1:1:1 to study medication (1% MIM-D3, 5% MIM-D3, or placebo) and dosed twice daily (BID) for 28 days. Key eligibility criteria included exacerbation in corneal staining and ocular discomfort in the Controlled Adverse Environment (CAESM) on two visits, separated by 1 week of BID dosing with artificial tears. Safety and efficacy were evaluated at baseline, throughout treatment, and for 2 weeks post-treatment. The pre-specified primary outcome measures were fluorescein corneal staining post-CAE at day 28 and diary worst symptom scores over 28 days. Secondary outcomes included the pre-, post-, and the change from pre- to post-CAE fluorescein and lissamine green staining in both corneal and conjunctival regions, as well as individual diary symptoms.
Results: The prespecified primary endpoints were not met. Compared with placebo, fluorescein corneal staining at day 28 was significantly improved (P < 0.05) in the 1% MIM-D3 group for the assessment of change from pre-CAE to post-CAE. In addition, following CAE exposure, patients in the 1% MIM-D3 group showed significant improvements versus placebo (P < 0.05) in inferior fluorescein and lissamine green staining after 14 and 28 days. Compared with placebo, patients in the 5% MIM-D3 group reported significantly lower daily diary scores for ocular dryness (P < 0.05). In a subgroup defined by higher symptom scores during the run-in period, significant treatment effects (P < 0.05) were observed for diary symptoms for both MIM-D3 doses. Ocular adverse events were mild and not considered to be treatment-related.
Conclusion: Treatment with topical ophthalmic MIM-D3 demonstrated protection against the effects of a CAE challenge on dry eye signs, reduced patient-reported diary symptoms, with a favorable safety profile.
Keywords: nerve growth factor, controlled adverse environment, Mimetogen
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