Treatment with LL‐37 is safe and effective in enhancing healing of hard‐to‐heal venous leg ulcers: a randomized,placebo‐controlled clinical trial

Venous leg ulcers (VLUs) are one of the most prevalent types of chronic wounds. The aim of this study was to determine the safety and dose–response efficacy of the human synthetic peptide LL‐37 in the treatment of hard‐to‐heal VLUs. This first‐in‐man trial included 34 participants with VLUs and comprised a 3‐week, open‐label, run‐in period on placebo, followed by a 4‐week randomized double‐blind treatment phase with twice weekly applications of LL‐37 (0.5, 1.6, or 3.2 mg/mL) or placebo, and a 4‐week follow‐up. The healing rate constants for 0.5 and 1.6 mg/mL of LL‐37 were approximately six‐ and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL). Square‐root transformed wound area data showed improved healing for the 0.5 and 1.6 mg/mL dose groups compared with pretreatment values (p < 0.001 and p = 0.011, respectively). Consistently, treatment with the two lower doses markedly decreased the mean ulcer area (68% for 0.5 mg/mL and 50% for 1.6 mg/mL groups). No difference in healing was observed between the groups receiving 3.2 mg/mL of LL‐37 and placebo. There were no safety concerns regarding local or systemic adverse events. In conclusion, topical treatment with LL‐37 for chronic leg ulcers was safe and well tolerated with the marked effect on healing predictors at the two lower doses warranting further investigations.