Efficacy and Safety Study of p144 to Treat Skin Fibrosis in Systemic Sclerosis
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|ClinicalTrials.gov Identifier: NCT00574613|
Recruitment Status : Completed
First Posted : December 17, 2007
Last Update Posted : February 11, 2013
|Condition or disease||Intervention/treatment||Phase|
|Skin Fibrosis||Drug: P144 Drug: placebo||Phase 2|
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 scleroderma, only the skin of fingers, hands, face and lower arms and legs is affected. On the contrary, patients with the diffuse cutaneous disease, skin changes will become generalized, involving initially the extremities and followed by the face and trunk. Rapid progression of these changes over a 2 to 3 year period is usually associated with a greater risk of visceral disease. After several years of disease, the skin may soften and return to normal thickness or become thin and atrophic.
There is currently no approved specific treatment for skin fibrosis in systemic sclerosis neither in the European Union nor the United States of America. P144 belongs to a peptide family that is able to inhibit TGF-β1 in both in vitro and in vivo models characterized by excessive TGF-β1 function. Topical application of P144 exerts a preventive effect precluding the induction of skin fibrosis and the accumulation of collagen in these animals and also has shown its therapeutic properties reducing the skin fibrosis and soluble collagen content in mice with established fibrosis.
The EMEA and FDA have granted P144 the orphan drug status for the treatment of systemic sclerosis. In this study, the percentage of reduction in the soluble collagen content and skin hardness (durometer) will be measured.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||56 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Phase II, Multicenter, Randomized, Double-blind, Intraindividually Placebo Controlled Clinical Trial, to Evaluate Efficacy and Safety of p144 Topical Administration for Skin Fibrosis in Patients With Systemic Sclerosis|
|Study Start Date :||September 2007|
|Actual Primary Completion Date :||November 2009|
|Actual Study Completion Date :||September 2010|
Cream 0,3 ml once a day (3 months)
|Placebo Comparator: 2||
Cream 0,3 ml once a day (3 months)
- The percentage of reduction in the soluble collagen content and skin hardness after three months relative to baseline. [ Time Frame: Three months ]
- Changes in the histological and immunohistochemical analyses of P144 and placebo treated skin, in the expression levels of different molecular markers and changes from baseline in the skin elasticity quantified by Cutometer. [ Time Frame: 3 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00574613
|Study Chair:||Marco Matucci, MD|
|Principal Investigator:||Thomas Krieg, MD|
|Principal Investigator:||Ulf Müller-Ladner, MD|
|Principal Investigator:||László Czirják, MD|
|Principal Investigator:||Christopher Denton, MD|
|Principal Investigator:||José Luis Pablos, MD|