Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies.

Abstract

BACKGROUND:

Research into mechanisms of skin scarring identified transforming growth factor beta3 (TGFbeta3) as a potential antiscarring therapy. We assessed scar improvement with avotermin (recombinant, active, human TGFbeta3).

METHODS:

In three double-blind, placebo-controlled studies, intradermal avotermin (concentrations ranging from 0.25 to 500 ng/100 microL per linear cm wound margin) was administered to both margins of 1 cm, full-thickness skin incisions, before wounding and 24 h later, in healthy men and women. Treatments (avotermin and placebo or standard wound care) were randomly allocated to wound sites by a computer generated randomisation scheme, and within-participant controls compared avotermin versus placebo or standard wound care alone. Primary endpoints were visual assessment of scar formation at 6 months and 12 months after wounding in two studies, and from week 6 to month 7 after wounding in the third. Investigators, participants, and scar assessors were blinded to treatment. Efficacy analyses were intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00847925, NCT00847795, and NCT00629811.

RESULTS:

In two studies, avotermin 50 ng/100 microL per linear cm significantly improved median score on a 100 mm visual analogue scale (VAS) by 5 mm (range -2 to 14; p=0.001) at month 6 and 8 mm (-29 to 18; p=0.0230) at month 12. In the third, avotermin significantly improved total scar scores at all concentrations versus placebo (mean improvement: from 14.84 mm [95 % CI 5.5-24.2] at 5 ng/100 microL per linear cm to 64.25 mm [49.4-79.1] at 500 ng/100 microL per linear cm). Nine [60%] scars treated with avotermin 50 ng/100 microL per linear cm showed 25% or less abnormal orientation of collagen fibres in the reticular dermis versus five [33%] placebo scars. After only 6 weeks from wounding, avotermin 500 ng/100 microL per linear cm improved VAS score by 16.12 mm (95% CI 10.61-21.63). Adverse events at wound sites were similar for avotermin and controls. Erythema and oedema were more frequent with avotermin than with placebo, but were transient and deemed to be consistent with normal wound healing.

INTERPRETATION:

Avotermin has potential to provide an accelerated and permanent improvement in scarring.

• Authors: Mark W J Ferguson, Jonathan Duncan, Jeremy Bond, James Bush, Piyush Durani, Karen So, Lisa Taylor, Jonquille Chantrey, Tracey Mason, Gaynor James, Hugh Laverty, Nick L Occleston, Abdul Sattar, Anna Ludlow, Sharon O'Kane
• Journal: Lancet (London, England) (Lancet) Vol. 373 Issue 9671 Pg. 1264-74 (Apr 11 2009) ISSN: 1474-547X [Electronic] England
• PMID: 19362676 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Transforming Growth Factor beta3

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Analysis of Variance
• Biopsy
• Chemistry, Pharmaceutical
• Cicatrix (pathology, prevention & control)
• Double-Blind Method
• Drug Administration Schedule
• Edema (chemically induced)
• Erythema (chemically induced)
• Female
• Humans
• Injections, Intradermal
• Male
• Middle Aged
• Premedication (methods)
• Severity of Illness Index
• Statistics, Nonparametric
• Transforming Growth Factor beta3 (adverse effects, chemistry, therapeutic use)
• Treatment Outcome
• Wound Healing (drug effects)
• Young Adult