Background: There is a significant unmet medical need for effective treatments that reduce scarring following injury or surgery, with patients indicating that they value any improvement in scarring. Currently, there are no registered pharmaceuticals or universally accepted treatments for reducing scarring. Previous phase I/II trials have shown that avotermin (transforming growth factor β3) is a new class of prophylactic medicine that improves scar appearance, both macroscopically and microscopically at the tissue level. The objective of this trial was to compare the appearance of scars following one or two doses of avotermin (at two dose levels) versus within-subject placebo and standard-care controls. All treatments were administered to the approximated margins of acute incisional wounds.
Methods: Healthy males, aged 18–45 years, were assigned to one of two treatments: avotermin 50ng or 200ng/100µL/linear cm/linear cm of wound margin. All subjects received three standardized 1cm incisional wounds on the inner aspect of each upper arm. Wounds were randomized to receive (into each wound margin): no injection (standard wound care only), a single intradermal injection of avotermin or placebo (immediately before surgery) or repeated doses of avotermin or placebo (immediately before surgery and 24 hours later). The study was powered to show treatment differences in the prespecified primary efficacy variable: the scoring of how closely scars resemble normal skin at Month 12. An Independent External Scar Assessment Panel (IESAP, Lay Panel) scored standardized, calibrated photographs of scars using a 100mm visual analogue scale (VAS). Within-subject differences in VAS scores between control- and avotermin-treated sites were analysed using a paired t-test (p<0.05 indicating significance).
Results: 71 Caucasian males were recruited, with 32 randomised into the 50ng group and 39 into the 200ng group. Age, body mass index and medical history were similar across treatment groups. The primary efficacy analysis showed that avotermin 200ng/100mL/linear cm, administered once or twice, achieved statistically significant improvements in scar appearance compared with controls (p<0.02 for comparisons with Placebo and Standard Care). The 50ng dose also showed statistically significant improvements in scar appearance versus placebo (p=0.0425). Results with the 200ng dose were supported by secondary endpoints, including those that involved ‘on-the-subject’ scar assessment by investigators. The incidence and profile of site-specific adverse events (AEs) were similar with avotermin, placebo and standard wound care. No withdrawals due to AEs or serious AEs related to avotermin occurred.
Conclusions: The primary objective was met. Compared with placebo and standard wound care, intradermal avotermin at 50 and 200ng/100µL/linear cm of wound margin produced statistically significant improvements in the appearance of scars resulting from acute incisional wounds with approximated margins and showed a favorable safety profile.