Safety and efficacy of a novel integrin inhibitor ALG-1007 topical ophthalmic solution for the treatment of dry eye disease

Session Details

Session Title: Cornea: Medical

Session Date/Time: Monday 16/09/2019 | 08:30-10:30

Paper Time: 09:48

Venue: Free Paper Forum: Podium 2

First Author: : E.Holland USA

Co Author(s): :    E. Donnenfeld   R. Lindstrom   A. Vardanyan   T. Adamyan   L. Karageozian   J. Aubel              

Abstract Details

Purpose:

ALG-1007 is a small synthetic peptide integrin inhibitor that interferes with Complement component 3, leukocyte adhesion and trans-endothelial migration which results in downregulation of inflammation. Preclinical studies demonstrated the reduction of cytokines associated with DED after treatment with ALG-1007. The purpose of this dose ranging study is to determine safety and dose response effect of ALG-1007 in patients with DED.

Setting:

Single site, hospital-based practice, multi-specialty clinic

Methods:

Prospective, open-label study human clinical trial. 40 eyes diagnosed with DED for at least 6 months were enrolled and assigned to 1 of 4 treatment doses (n=10, each group): 0.125, 0.25, 0.4 and 0.6% of ALG-1007 (Allegro Ophthalmics, San Juan Capistrano, CA) in a lubricating ophthalmic topical solution, 1 drop 2xday. Subjects were followed at weeks 1, 2, 4, 6, 8, 10 and 12. Outcome measures were: tear break up time (TBUT), SICCA total ocular staining score (0=no staining, 12=severe), corneal and nasal conjunctival staining score (0=no staining, 3=severe), and reported symptoms using the visual analog scale (VAS) symptom index.

Results:

Mean change from baseline (CFB) in TBUT were 2.0, 3.4, 0.5 and 6.7 secs in groups 0.125, 0.25, 0.4 and 0.6%, respectively. The mean CFB in nasal conj staining were -0.2, -0.7, -0.9, and -1.6, respectively. The mean CFB in cornea staining were -0.9, -1.4, -0.1, and -1.4, respectively. The mean CFB in total ocular staining were -1.5, -3.5, -2.5, and -5.1, respectively. The symptom score correlated negatively with TBUT and positively with the other 3 measures. The dose difference between 0.125 and 0.6% in TBUT, nasal and total staining were significantly greater at the high dose (p < 0.05).

Conclusions:

This study demonstrates that ALG-1007 exhibits a dose response curve with clinical and statistically significant efficacy in multiple objective and subjective measures. Although the study does not have a vehicle control, the results indicate that the active ingredient (not the vehicle) is effective in improving signs and symptoms of DED in a statistically significant manner when comparing the 0.125% dose vs the 0.6% dose. The drug was well-tolerated with no drug-related SAEs, blurring of vision nor ocular irritation. A Phase 2 study has been initiated using higher doses. Results from the study will also be presented.

Financial Disclosure:

is employed by a competing company, receives consulting fees, retainer, or contract payments from a competing company, receives consulting fees, retainer, or contract payments from a company producing, developing or supplying the product or procedure presented