title: Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of ophthalmic MIM-D3, a tyrosine kinase TrkA receptor agonist, in patients with dry eye.
  
  
  METHODS
  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 (CAE(SM)) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Mimetogen Pharmaceuticals Inc, Montreal, QC, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Meerovitch
authors.forename: Gail
authors.initials: G
authors.lastname: Torkildsen
authors.forename: John
authors.initials: J
authors.lastname: Lonsdale
authors.forename: Heidi
authors.initials: H
authors.lastname: Goldfarb
authors.forename: Teresa
authors.initials: T
authors.lastname: Lama
authors.forename: Garth
authors.initials: G
authors.lastname: Cumberlidge
authors.forename: George W
authors.initials: GW
authors.lastname: Ousler
keywords: Mimetogen; controlled adverse environment; nerve growth factor