Early Clinical Development of EBI-005, a Potent Interleukin-1 (IL-1) Receptor-1 (R1) Blocker for Topical Ocular Treatment of Dry Eye Disease (DED)

Abstract

Purpose: Herein we describe a stable formulation of EBI-005, a novel, potent IL-1R1 inhibitor that was optimized to treat ocular surface disorders, such as DED. In this Phase 1 safety study, EBI-005 was administered topically to the eyes of healthy volunteers. Multiple lines of evidence indicate that IL-1R1 blockade is therapeutically active in reducing the signs and symptoms of DED, including a Phase 2 clinical study using a prototype topical ocular IL-1R1 blocker. In support of this and other clinical studies, EBI-005 was well-tolerated in six-week mouse and rabbit GLP toxicology studies.

Methods: In a double-masked, placebo-controlled study, healthy volunteers were administered one drop of placebo, 5 or 20 mg/mL EBI-005 three times in one day. Each dose cohort contained eight subjects, six were randomized to receive drug and two randomized to placebo. Subjects receiving EBI-005 were administered drug in only one eye, the second eye received placebo. Safety assessments included: adverse event reporting, visual acuity (best corrected vision), slit lamp examination, intraocular pressure, dilated fundus examination, ocular surface sensitivity (Cochet-Bonnet esthesiometry), corneal pachymetry, ocular surface microbiology, and serum laboratory testing. Subjects were confined to a phase one unit for 4 days. A safety committee made up of the principal investigator, medical director and independent safety monitor reviewed the clinical data prior to escalating to the 20 mg/ml dose.

Results: Administration of one drop of 5 or 20 mg/mL EBI-005 three times over one day was generally well-tolerated in healthy volunteers and adverse events were not substantially different than placebo. Visual acuity, slit lamp examination, ocular surface sensitivity and ocular surface microbiology were not significantly changed after administration of EBI-005.

Conclusions: Stable formulations of 5 and 20 mg/mL EBI-005 were well-tolerated in healthy volunteers when administered three times in a day. These results supported the start of an ongoing six-week study designed to assess the safety and biological activity of EBI-005 in patients with DED.

Keywords: 490 cytokines/chemokines • 557 inflammation • 479 cornea: clinical science