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Connective tissue growth factor (CTGF) levels are up-regulated in wounded skin and are thought to play a major role in scar formation. An antisense oligonucleotide targeting CTGF was evaluated in adult patients undergoing hypertrophic scar revision surgery, to determine effects on reducing the severity of subsequent scars.In a randomized, double-blind, within-subject, placebo-controlled study, 23 female subjects (aged 28 to 55 years) with bilateral, symmetric, hypertrophic surgical scars of the breast underwent scar revision surgery. The resulting breast incisions were randomized to receive EXC 001 (5 mg/cm) or placebo injected intradermally at postsurgery weeks 2, 5, 8, and 11. Scar severity assessments were performed at weeks 12 and 24 by an expert panel using blinded photographs, and by physicians and subjects using a scar scoring scale, the Patient and Observer Scar Assessment Scale. An assumption of the design is that within-subject variance would be small and that whatever within-subject variance there was would be controlled through the randomization process.EXC 001 significantly reduced scar severity at both 12 and 24 weeks after scar revision surgery in all three measures (expert panel and physician Patient and Observer Scar Assessment Scale, p < 0.001; Patient and Observer Scar Assessment Scale, p < 0.003).This study provided positive preliminary data that intradermal injection of EXC 001 produced a significant reduction in severity of postsurgical skin scars, as measured by physicians, subjects, and an expert panel. This study provided evidence that suppression of CTGF could be a viable strategy for hypertrophic scar reduction therapy and that further study of the antisense oligonucleotide EXC 001 was indicated.Therapeutic, II.