Effects of a New Enzymatic Debrider (SN514-066b) on Eschar Protein Digestion, Burn Wound Debridement, and Healthy Skin Irritation.

Abstract

Objective: SN514 is a thermolysin-like enzyme under development as a debrider. Preclinical and non-clinical studies supported a first in human healthy volunteer study to predict the need for protection of periwound skin. Approach: Pharmacologic activity testing compared in vitro digestion of collagen, fibrin, and elastin with relevant enzymes. A Yorkshire pig model of burn injury was used to evaluate debridement over 10 days and effects on intact skin. A human 21-day cumulative irritation study using Webril patches taped to the backs of 38 healthy adult volunteers compared four enzyme concentrations (0.10%, 0.20%, 0.40%, and 0.80% w/w) with the hydrogel vehicle, saline (low irritant control), and 0.2% sodium lauryl sulfate (positive irritant control) using randomized placements and blinded evaluation. Results: SN514 showed excellent digestion of fibrin, elastin, and collagen in vitro. Burn wound studies in Yorkshire pigs showed efficient eschar debridement with minimal periwound erythema. Direct treatment on intact porcine skin for 5 days produced no to limited erythema. The preclinical findings of minimal irritation with SN514 were verified by a Phase 1 first-in-human 21-day cumulative skin irritation test. Irritation was observed to increase stepwise by concentration, confirming formulation accuracy. Each enzyme concentration was found to be "possibly mild in use" (Berger and Bowman method). No treatment emergent adverse events were observed during the study. Innovation: A fast-acting enzyme with a favorable irritation profile, prepared as a stable, ready to use hydrogel formulation, overcomes many recognized shortcomings of enzyme debriders. Conclusion: The overall findings support clinical dose range testing for tolerance and preliminary efficacy.