Open Label Extension (OLE) for the Patients Treated in the ISD002-P144-07 Study
Condition: Skin Fibrosis
MeSH terms: Fibrosis
Study type: Interventional
Phase: Phase 2

Summary: 
      Transforming growth factor-beta 1 is consistently over expressed in most fibrotic diseases
      and displays a variety of profibrotic effects in fibroblasts(25, 26). Activation of TGF-beta
      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-beta 1 i 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-beta1 mRNA and protein levels has been
      described in these processes. Peptide 144 (P144)is a acetic salt of a 14mer peptide from
      human TGF-beta1 type III receptor (betaglycan). P144 TGF-beta1-inhibitor has been
      specifically designed to block the interaction between TGF-beta1 and TGF-beta1 type III
      receptor, thus blocking its biological effects. P144 has shown significant antifibrotic
      activity in mice receiving repeated sucutaneous injections of bleomycin, a widely accepted
      animal model of human scleroderma, and could contribute to the development. The aim of the
      study is to asses the long-term safety of topical application of P144 cream in the treatment
      of skin fibrosis in patients with systemic sclerosis in an extension open-label treatment
      period of 6 additional months.
    

Detailed description: 
      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-beta1; TGF-beta1 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 are 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. The
      EMEA and FDA have granted P144 the orphan drug status for the treatment of systemic
      sclerosis. The primary objective is to assess the long-term safety of P144 crem topically
      administered in skin manifestations of systemic sclerosis patients in terms of the incidence
      of treatment related adverse events during the extension period of six months.
    

Intervention name(s): P144 cream
Intervention type(s): Drug
Intervention description(s): P144 cream 0.03% will be used once a day during the whole extension period of 6 months. The patient will apply the cream by him/herself or with a help of a person uniformly in a 10% maximum affected surface until absorption
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: skin fibrosis; systemic scleroderma; systemic sclerosis; p144; orphan drug