Silk-Derived Protein-4 versus vehicle control in treating patients with moderate to severe dry eye disease: a randomized clinical trial.

ABSTRACT

PURPOSE: In this study the safety and efficacy of silk-derived protein 4 (SDP-4), also known as amlisimod, eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, anti-inflammatory wetting agent that enhances coating on the ocular surface. DESIGN: Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle-controlled study. METHODS: In the first cohort (N=305), patients were randomized 1111 to SDP-4 (0.1%, 1%, 3% wt./wt.) or vehicle control and dosed two times per day (BID), while in the second cohort patients were randomized 11 with 1% wt./wt. SDP-4, the best performing formulation from the first cohort, or vehicle control BID (N=151). Diagnosed DED patients were treated in the United States between April 2019 and May 2021. The first cohort of subjects had moderate to severe baseline symptoms, while the second cohort had moderate baseline symptoms to study the impact of baseline symptoms on SDP-4 performance. Key sign and symptom end points were mean change from baseline in TBUT and total SANDE score (0-100 visual analog scale) throughout the study. RESULTS: SDP-4 (1%) significantly increased TBUT vs the vehicle control (P<0.05) at days 28 and 56 in the first cohort, and patient symptomatology from baseline was reduced by 46% based on subject reported SANDE VAS scores at day 84. Patients with more severe baseline DED symptoms experienced a significantly greater amount of relief than when compared to patients with moderate DED (P<0.05). All treatment groups were well tolerated with a 2.6% total discontinuation rate. CONCLUSIONS: To the best of our knowledge, this was the first-in-human use of SDP-4 in a clinical trial. SDP-4 is a first-in-class protein ingredient that offers a safe and multi-modal treatment approach for alleviating severe DED symptoms within a novel formulation.