Randomized phase II clinical trial of avotermin versus placebo for scar improvement

Abstract

Scarring is a major problem following skin injury. In early clinical trials, transforming growth factor β3 (avotermin) improved scar appearance. The aim of this study was to determine whether an injection of avotermin at the time of wound closure is effective in improving scar appearance. Study RN1001-0042, a double-blind, randomized, within-patient, placebo-controlled trial, investigated the efficacy and safety of four doses of avotermin given once. Patients undergoing bilateral surgery to remove varicose leg veins by saphenofemoral ligation and long saphenous vein stripping were enrolled at 20 European centres. A total of 156 patients were randomized to receive one of four doses of avotermin (5, 50, 200 or 500 ng per 100 µl, at 100 µl per linear cm of wound margin), administered by intradermal injection to the groin and distal wound margins of one leg; placebo was administered to the other leg. Scar appearance was evaluated by an independent panel of lay people (lay panel), investigators and patients. The primary efficacy variable was lay panel Total Scar Score (ToScar), derived from visual analogue scale scores for groin scars between 6 weeks and 7 months. Avotermin 500 ng significantly improved groin scar appearance compared with placebo (mean lay panel ToScar difference 16·49 mm; P = 0·036). Avotermin 500 ng per 100 µl per linear cm of wound margin given once is well tolerated and significantly improves scar appearance.