Volume 373, Issue 9671, Pages 1264-1274 (April 2009) Prophylactic administration of avotermin for improvement of skin scarring: three double- blind, placebo-controlled, phase I/II studies  Prof Mark WJ Ferguson, DMedSci, Jonathan Duncan, MD, Jeremy Bond, MB, James Bush, MB, Piyush Durani, MD, Karen So, MB, Lisa Taylor, MB, Jonquille Chantrey, MB, Tracey Mason, PhD, Gaynor James, MSc, Hugh Laverty, PhD, Nick L Occleston, PhD, Abdul Sattar, PhD, Anna Ludlow, PhD, Sharon O'Kane, PhD  The Lancet  Volume 373, Issue 9671, Pages 1264-1274 (April 2009) DOI: 10.1016/S0140-6736(09)60322-6 Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 1 Treatment differences (placebo–avotermin) in total scar score (primary endpoint in study 0036) Total scar score is a summary measure of VAS scores assigned by the IESAP (lay) to wound scars from week 6 to month 7. The Lancet 2009 373, 1264-1274DOI: (10.1016/S0140-6736(09)60322-6) Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 2 Ranking of scar pairs at month 7 in study 0036 Digital images of matched scar pairs were ranked by the IESAP (lay) with LOCF (A) and IESAP (clinical) (B). The Lancet 2009 373, 1264-1274DOI: (10.1016/S0140-6736(09)60322-6) Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 3 Ranking of scar pairs in study 0036 by the investigator over time in the 500 ng dose group The Lancet 2009 373, 1264-1274DOI: (10.1016/S0140-6736(09)60322-6) Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 4 Paired photographs of wound scars treated with avotermin or control treatment (placebo or standard wound care) The data below the photographs show the VAS scores assigned by the external panel that assessed photographic images of scars and the investigator (plastic surgeon) who assessed the scars directly on the participant. (A) Incised wound scars from a 37-year-old white man photographed at month 12 after wounding (study 1002) treated with avotermin 50 ng/100 μL per linear cm wound margin and placebo. (B) Incised wound scars from a 67-year-old white woman photographed at month 6 after wounding (study 1005) treated with avotermin 50 ng/100 μL per linear cm wound margin and standard care. The black dots indicate the ends of the original wound site. (C) Incised wound scars from a 71-year-old white woman photographed at month 7 after wounding (study 0036) treated with avotermin 500 ng/100 μL per linear cm wound margin and placebo. The Lancet 2009 373, 1264-1274DOI: (10.1016/S0140-6736(09)60322-6) Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 5 Scar redness over time from study 1002 (men aged 18–45 years) (A) and study 1005 (participants aged ≥60 years) (B) Scar redness over time was assessed by the internal panel reviewing standardised scar photographs. p value derived from a test for association between treatments based on the month that redness fades. The Lancet 2009 373, 1264-1274DOI: (10.1016/S0140-6736(09)60322-6) Copyright © 2009 Elsevier Ltd Terms and Conditions

Figure 6 Histology of matched scars at month 6 after wounding These scars developed from avotermin-treated and placebo-treated incised wounds made in the same participant in study 1005. Tissue sections (5 μm thick, formalin-fixed) were stained with Masson's Trichome. Arrows indicate the edges of the scar. e=epidermis. nd=normal dermis. (A) In the placebo-treated scar, an abnormal parallel organisation of collagen is present in the papillary dermis, and abnormal whorls of scar-tissue collagen are diagnostic of a hypertrophic (poor) scar. (B) By contrast, in the avotermin-treated scar, collagen shows a uniform basket-weave organisation, which is similar to that in normal skin. The Lancet 2009 373, 1264-1274DOI: (10.1016/S0140-6736(09)60322-6) Copyright © 2009 Elsevier Ltd Terms and Conditions