Efficacy and Safety Study of p144 to Treat Skin Fibrosis in Systemic Sclerosis

Summary

Transforming growth factor-beta 1 (TGF-β1) is consistently over expressed in most fibrotic diseases and displays a variety of profibrotic effects in fibroblasts. Activation of TGF-β receptors induces the activation of several kinase signalling cascades leading to the phosphorylation of SMAD proteins as well as to the activation of SMAD-independent kinases that collectively activate ECM synthesis and fibroblast growth and differentiation into myofibroblasts. TGF-β1 is one of the main mediators in the fibrotic process, associated to both scarring and a long list of pathologies related to chronic inflammation and which affect all type of organs and tissues. An increase in TGF-β1 mRNA and protein levels has been described in these processes. Peptide 144 (P144) is the acetic salt of a 14mer peptide from human TGF-β1 type III receptor (betaglycan). P144 TGF-β1-inhibitor has been specifically designed to block the interaction between TGF-β1 and TGF-β1 type III receptor, thus blocking its biological effects. P144 has shown significant antifibrotic activity in mice receiving repeated subcutaneous injections of bleomycin, a widely accepted animal model of human scleroderma, and could contribute to the development. The purpose of this study is to asses the efficacy and safety of topical application of P144 in the treatment of skin fibrosis in patients with systemic sclerosis.

Timeline

Start

2007-09

Primary completion

2009-11

Completion

2010-09

Publications

• Background Denton CP, Black CM. Scleroderma--clinical and pathological advances. Best Pract Res Clin Rheumatol. 2004 Jun;18(3):271-90. doi: 10.1016/j.berh.2004.03.001.
• Background White B, Bauer EA, Goldsmith LA, Hochberg MC, Katz LM, Korn JH, Lachenbruch PA, LeRoy EC, Mitrane MP, Paulus HE, et al. Guidelines for clinical trials in systemic sclerosis (scleroderma). I. Disease-modifying interventions. The American College of Rheumatology Committee on Design and Outcomes in Clinical Trials in Systemic Sclerosis. Arthritis Rheum. 1995 Mar;38(3):351-60. doi: 10.1002/art.1780380309.
• Background Querfeld C, Eckes B, Huerkamp C, Krieg T, Sollberg S. Expression of TGF-beta 1, -beta 2 and -beta 3 in localized and systemic scleroderma. J Dermatol Sci. 1999 Sep;21(1):13-22. doi: 10.1016/s0923-1811(99)00008-0.
• Background Kissin EY, Schiller AM, Gelbard RB, Anderson JJ, Falanga V, Simms RW, Korn JH, Merkel PA. Durometry for the assessment of skin disease in systemic sclerosis. Arthritis Rheum. 2006 Aug 15;55(4):603-9. doi: 10.1002/art.22093.

Drugs

Indications