Evaluation of LL‐37 in healing of hard‐to‐heal venous leg ulcers: A multicentric prospective randomized placebo‐controlled clinical trial

Abstract

Many patients with venous leg ulcers do not reach complete healing with compression treatment alone, which is current standard care. This clinical trial HEAL LL-37 was a phase IIb double-blind, randomized, placebo-controlled study, with the aim to evaluate the efficacy and safety of a new drug LL-37 for topical administration, in combination with compression therapy, in 148 patients suffering from hard-to-heal venous leg ulcers. The study had three arms, consisting of two groups treated with LL-37 at concentrations of 0.5 or 1.6 mg/mL, and a placebo cohort. Patients had a mean age of 67.6 years, a median ulcer duration of 20.3 months, and a mean wound size at the time of randomization of 11.6 cm 2 .Efficacy analysis performed on the full study population did not identify any significant improvement in healing in patients treated with LL-37 as compared with the placebo. In contrast, a post hoc analysis revealed statistically significant improvement with LL-37 treatment in several interrelated healing parameters in the subgroup of patients with large target wounds (a wound area of at least 10 cm 2 at randomization), which is a known negative prognostic factor for healing. The study drug was well tolerated and safe in both dose strengths. In summary, this clinical trial did not detect any significant differences in healing of venous lower leg ulcers in the entire study cohort comparing patients treated Krystyna Twardowska-Saucha is deceased.

Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens

“…Lactate dehydrogenase (LDH) release assays showed that As-CATH8 and Gg-CATH5 were moderately cytotoxic against human bronchial epithelial (HBE) cells and peripheral blood mononuclear cells (PBMCs) ( Supplementary Figure S3 ), at the highest concentrations tested (5 and 10 μM). This effect was similar to that observed for the natural human cathelicidin LL-37, which has been used in a phase 1 human clinical trial [ 31 ]. In contrast, the crocodylian peptides As-CATH7 and Gg-CATH7 showed low cytotoxicity against both cell types, comparable to the immunomodulatory peptide IDR-1018 used as control.…”

A stable cyclized antimicrobial peptide derived from LL-37 with host immunomodulatory effects and activity against uropathogens

“…In the context of UTI, AMPs such as defensins [ 8 ], the ribonuclease A superfamily [ 9 ] and LL-37, the only member of the cathelicidin family found in humans [ 10 ], are part of the innate immunity protecting the host from invading pathogens. Currently, synthetic LL-37 is being used in clinical trials treating venous leg ulcers [ 11 , 12 ]. Despite the interesting bioactivities of LL-37, its direct utility in a clinical setting has been hampered due to its toxicity to human cells and proteolytic instability [ 13 , 14 ].…”

Antimicrobial Peptides—Mechanisms of Action, Antimicrobial Effects and Clinical Applications

“…An earlier randomized, placebo-controlled trial demonstrated that the topical application of LL-37 can enhance the healing rate of chronic venous leg ulcers [ 139 ]. However, that was not corroborated in a newer trial, and it was still concluded that this human synthetic peptide could offer a certain treatment benefit in individuals with large ulcers [ 140 ]. Although the exact mechanism of wound repair is still elusive, there is a supposed effect of LL-37 in modulating the inflammatory response and driving angiogenesis together with re-epithelialization [ 125 , 141 ].…”