Abstract
Purpose :
The novel compound SkQ1 is a positively charged antioxidant with a unique mechanism of action capable of acting as a sustained free-radical scavenger. As such, it represents a unique treatment approach for conditions associated with oxidative stress, including age-related ocular disorders such as dry eye. In a previous Phase 2 study SkQ1 demonstrated efficacy in reducing both the signs and symptoms in dry eye subjects. This Phase 3 study was designed to confirm efficacy of mitochondrial reactive oxygen species (mtROS) scavenger SkQ1 in dry eye disease patients both environmentally and under controlled adverse environment challenge.
Methods :
This was a multi-center, double-masked, randomized, placebo-controlled study comprising 5 visits over the course of approximately 9 weeks. Qualified subjects (n=444) were randomized 1:1:1 to receive either high dose SkQ1 ophthalmic solution (1.55ug/mL), low dose SkQ1 ophthalmic solution (0.155ug/mL), or placebo (vehicle of SkQ1 ophthalmic solution). The primary endpoints were change from baseline (Visit 2) to Visit 5 (Day 57) in central corneal fluorescein staining and change from baseline (Visit 2) to Visit 5 (Day 57) in grittiness symptom. Secondary outcome measures included various symptoms, lissamine green staining, tear film break-up time, Schirmer's test and conjunctival redness measured both environmentally and during controlled adverse environment challenge. Biomarkers of oxidative stress and inflammation were also measured in tear samples.
Results :
Previous differences in dry eye sign treatment effects were observed for total FCS scores in the ITT population when compared pre- and post-CAE® at earlier timepoints (28 days, p=0.0452) so we hypothesized that longer duration and a focus on central corneal staining would highlight the treatment effects in this study. Similarly, differences in dry eye symptom treatment effect were observed for ocular discomfort on day 28, a longer duration in the Phase 3 study protocol highlights treatment effects in symptom relief.
Conclusions :
SkQ1 ophthalmic solution is the first in class drug designed for protection of ocular surface from oxidative stress at mitochondrial level. Refinements in trial design and primary endpoints described here should provide support for the hypothesis that subjects with dry eye achieve relief in both signs and symptoms of the disease with SkQ1 therapy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.