Clinical Trial: Tolerability and Bioavailability of the P144 Peptide Inhibitor of TGF-β1 After Topical Administration in Healthy Volunteers
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Multicentre, Placebo-Controlled, Multi-Dosis, Phase I Clinical Trial to Evaluate the Tolerability and Bioavailability of TGF β1 Inhibitor Peptide 144 After Topical Ad
Brief 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 assess the tolerability and safety of topical application of P144 in healthy volunteers.
Detailed Summary:
Three different formulations of DIGNA P144 cream (containing 100 μg/mL, 200 μg/mL and 300 μg/mL) will be tested in healthy volunteers. Tolerability evaluation is performed through the specific cutaneous tolerability visual scale of Frosch and Kligman. Safety assessment is carried out by studying vital signs, physical examination, by performing laboratory tests, electrocardiogram and reporting any adverse events experienced. This is the first time that P144 will be administered in humans. The topical route has been chosen since the indication for which P144 is going to be clinically developed will be cutaneous sclerosis associated to scleroderma.
Systemic sclerosis or scleroderma is a multisystemic disorder characterized by the excessive synthesis and deposition of extracellular matrix proteins that result in the fibrosis of skin and visceral organs (including gastrointestinal tract, lungs, heart and kidneys).
The pathogenesis of scleroderma is complex and still poorly understood, but major pathways involved in the development of the condition are microvascular and immunological abnormalities, as well as dysregulation of fibroblast activity. One of the key molecules involved in the pathogenesis of skin fibrosis is the TGF-β1; TGF-β1 is a cytokine directly responsible for fibroblasts proliferation and collagen and extracellular matrix overproduction.
The affected skin of patients with systemic sclerosis gradually becomes firm, thickened and eventually tightly bound to underlying subcutaneous tissue (indurative phase). It loses hair, oil, and sweat glands becoming dry and coarse. Changes begin distally in the extremities and advance proximally. Lesions develop over a period of time varying from months to a few years. In patients with limited scleroderm
Sponsor: ISDIN
Current Primary Outcome: Tolerability evaluation was performed through the specific cutaneous tolerability visual scale of Frosch and Kligman. [ Time Frame: Twenty-one days ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Safety assessment was carried out by studying vital signs, physical examination, by performing laboratory tests, electrocardiogram and reporting any adverse events experienced. Bioavailability of P 144 in serum. [ Time Frame: Twenty-one days ]
Original Secondary Outcome: Same as current
Information By: ISDIN
Dates:
Date Received: April 7, 2008
Date Started: March 2007
Date Completion:
Last Updated: November 4, 2008
Last Verified: November 2008
