S42909 is an inhibitor of β-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. S42909 has demonstrated vascular anti-inflammatory properties by preventing leukocyte endothelial cell adhesion, and vascular protection by reducing the expression of the endothelial cell dysfunction marker plasminogen activator inhibitor-1 (PAI-1) and decreasing matrix metalloproteinase-2 (MMP-2) activity. It is initially proposed for development for the oral treatment of venous leg ulcers.
During its preclinical development, S42909 has demonstrated promising pharmacological properties on wound healing, indicating that the compound may represent a potentially significant clinical advance in the treatment of venous lower limb ulcers by correcting the microcirculatory disorders associated with venous disease. Moreover, improvement of microcirculation should contribute to a better oxygenation of the damaged tissue, thus favouring ulcer healing.
Ongoing Clinical Trial
ILKOS THERAPEUTIC INC. is the sponsor of a global Phase 2a dose-finding study of S42909 on venous leg ulcer healing. This proof of concept study is a randomized, double-blind, placebo-controlled, multicentre study conducted at approximately 55 sites across Canada, Europe and the United States.
The objective of this study is to investigate if S42909 has an effect on the healing of venous leg ulcers (proof of concept) and to explore the relationship between dose and effect of S42909 on venous leg ulcer healing on top of standardized compression and local wound care.
The current study has been designed using the relative reduction of the reference ulcer (RU) area after four weeks of treatment as the primary efficacy endpoint. Secondary endpoints will also explore the effect of S42909 on improving pain related to venous leg ulcer and in decreasing analgesic drug consumption related to venous leg ulcer. The pharmacokinetics of S42909 and its metabolites will also be assessed in patients after repeated oral administration of S42909, and the safety of each tested dose of S42909 will also be evaluated.
Up to 204 eligible participants with an active venous leg ulcer will be randomized into one of 5 dose groups or a placebo control group in a 1:1:1:1:1:1 ratio: placebo, S42909 100 mg/day, 200 mg/day, 400 mg/day, 800 mg/day and 1200 mg/day. In all treatment groups, participants will be treated with S42909 on top of standard of care: compression and local wound care. To apply uniform standard of care procedures, high compression stockings (compression level of 35-40 mmHg) with individually adapted stocking sizes will be provided to all participants selected in the study.
Treatment duration will include 3 periods: a run-in period of 14 days, a treatment period of 6 weeks and a follow-up period of 2 weeks, for a total of 10 weeks.
Additional information on the S42909 proof of concept study can be found at www.clinicaltrials.gov, with the NCT Identifier #03077165.