Abstract
Purpose :
Dry eye disease involves ocular surface pathologies in which inflammation plays a central role. This study examined the potential of HL036, a molecularly engineered TNF receptor 1 fragment, as a therapy for relief of the signs and symptoms of dry eye. HL036 was specifically developed for ophthalmic topical use with tissue distribution, stability, and potency optimized for treatment of dry eye disease.
Methods :
This multicenter, randomized, prospective, double-masked, placebo-controlled study employed a controlled adverse environment challenge (CAE™) model. Following a 2 week placebo run-in, subjects were randomized to either 0.10% HL036, 0.25% HL036, or placebo twice daily, with 5 subsequent visits over 8 weeks. CAE challenge was used for screening and efficacy evaluations. Primary efficacy endpoints were fluorescein inferior corneal staining and ocular discomfort measured by 0-4 Ora Calibra™ scales. Secondary endpoints included lissamine staining, tear-film break-up time, a visual analog ocular discomfort, and daily symptom scores measured by 0-5 Ora Calibra™ scale. Safety measures included visual acuity, slit-lamp evaluation, dilated funduscopy, IOP, and drop comfort assessments.
Results :
Of 150 subjects enrolled, 138 completed the study. Corneal staining (pre- to post-CAE change) was reduced by both HL036 doses, and was significantly reduced at day 29 (treatment difference -0.38 units, p=0.0270) and at day 57 (difference -0.30 units, p=0.0486) for 0.25% HL036. Ocular discomfort (pre-CAE change) scores also improved with both HL036 doses, and were significantly improved at day 8 (difference -0.40, p=0.0391), day 15 (difference -0.40, p=0.0385) and day 57 (difference -0.40, p=0.0608) for 0.1% HL036. Symptom improvements were also seen in daily diary scores, with notable reductions in burning and stinging. Adverse events (n=16, 10.7%) were mild, self-limiting, and resolved within a week. There were no serious adverse events. HL036 demonstrated excellent tolerability and drop comfort.
Conclusions :
No currently marketed dry eye therapies target pro-inflammatory cytokines. In this study HL036, a TNF-α receptor fragment, ameliorated both signs and symptoms of dry eye. HL036 demonstrated an early onset of action at both tested doses, and displayed an excellent safety and efficacy profile. Results support the continued development of this promising therapy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.