A randomized double-blind placebo-controlled Phase 1 trial of PXS-6302, a topical lysyl oxidase inhibitor, in mature scars

Skin scars are a significant clinical challenge, with poor appearance and increased tissue stiffness affecting both physical and psychological wellbeing. Lysyl oxidases are a family of enzymes that catalyze collagen crosslinking, a key factor in scar pathophysiology. Here we report a randomized, double-blind, placebo-controlled Phase 1 clinical trial to assess the safety and tolerability of PXS-6302, a topical pan-lysyl oxidase inhibitor, in treating mature scars (ACTRN12621001545853). Fifty participants with scars were enrolled and PXS-6302 or placebo cream applied to a 10 cm2area for three months. No severe adverse events were reported. All treatment-related adverse events (AEs) were localized skin reactions. Treatment with PXS-6302 significantly inhibited lysyl oxidase activity (66%). Hydroxyproline (a marker for collagen) and total protein concentration in the scar were significantly reduced in the PXS-6302 treatment group compared to placebo. Optical coherence tomography (OCT) was used to measure vascularity and attenuation (a marker of extracellular matrix composition). PXS-6302 treatment significantly increased vessel density at 3 months compared to baseline. Tissue attenuation was also significantly increased in PXS-6302 treated participants compared to baseline, suggesting extracellular matrix was becoming increasingly similar to normal skin. No significant differences between placebo and PXS-6302 treatment groups were observed in Patient Observer Scar Assessment Scale (POSAS) scores at study conclusion. To our knowledge, this study represents the first demonstration of a safe and effective pharmaceutical intervention that significantly improves the molecular composition of established scar extracellular matrix in humans. Pan-lysyl oxidase inhibition therefore represents a potential paradigm shift for the amelioration of scarring. One Sentence SummaryMature scars remodeled after treatment with a topical cream for three months.