A randomized, double-blind, placebo-controlled phase 1 trial of the topical pan–lysyl oxidase inhibitor PXS-6302 in mature scars

Skin scars remain a substantial clinical challenge because of their impact on appearance and psychological well-being. Lysyl oxidases catalyze collagen cross-linking, a key factor in scar development. Here, we report a randomized, double-blind, placebo-controlled phase 1 study to assess the safety and tolerability of PXS-6302, a topical pan–lysyl oxidase inhibitor, in treating mature scars (ACTRN12621001545853). Fifty participants were enrolled across two cohorts: Cohort 1 (open label, n = 8) applied PXS-6302 (2%) daily, and cohort 2 (n = 42) was randomized 1:1 to apply PXS-6302 (2%) or placebo three times per week to a 10-square-centimeter area of scar for 3 months. No severe adverse events (AEs) were reported. Mild to moderate localized skin reactions were the only treatment-related AEs, leading to discontinuation by six participants. Treatment with PXS-6302 three times per week reduced lysyl oxidase activity by 66% and decreased hydroxyproline (a marker for collagen) and total protein concentrations in scar biopsies compared with placebo. Optical coherence tomography showed increased microvessel density and tissue attenuation [a marker of extracellular matrix (ECM) composition] at 3 months compared with the baseline, suggesting ECM remodeling toward unscarred skin architecture. No significant differences in Patient Observer Scar Assessment Scale (POSAS) scores were observed between groups after 90 days of treatment once baseline imbalances were accounted for. Together, these data showed that topical pan–lysyl oxidase inhibition was generally well tolerated and altered some measures of the ECM in mature scars, supporting the advancement of this treatment into phase 2 trials.