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Open Label Extension (OLE) for the Patients Treated in the ISD002-P144-07 Study
This study is currently recruiting participants.
Verified by ISDIN, October 2008
Sponsors and Collaborators: ISDIN
DigNA Biotech
Information provided by: ISDIN
ClinicalTrials.gov Identifier: NCT00781053
  Purpose

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.


Condition Intervention Phase
Skin Fibrosis
Drug: P144 cream
Phase II

MedlinePlus related topics: Scleroderma
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety Study
Official Title: Open Label Extension (OLE) for the Patients Treated in the ISD002-P144-07 Study With P144 Topical Adminsitration for Skin Fibrosis in Patients With Systemic Sclerosis

Further study details as provided by ISDIN:

Primary Outcome Measures:
  • Assess the long-term safety of digna P144 cream topically administered in skin manifestations of systemic sclerosis patients. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Quality o life assessment, skin induration and hardness. In a subgroup of patients pharmacokinetic and elasticity will be measured. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 98
Study Start Date: July 2008
Estimated Study Completion Date: July 2009
Estimated Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
P144 cream: Experimental
P144 cream 0.03% will be used once a day during the whole extension period of 6 months.
Drug: P144 cream
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Previous participation and finalization of treatment period of the ISD002-P144-07 study without clinical relevant safety issues medically evaluated by the investigator.
  2. For female subjects with childbearing potential: use of a known highly effective method of birth control, defined as those which results in a low failure rate: i.e. less 1% per year, (contraceptive pills, intrauterine contraceptive device, implants, vasectomized partner or sexual abstinence), for at least the extension study period and one month after the end of the extension study.
  3. For male subjects with partners of childbearing potential:

    use of appropriate contraceptive methods (vasectomy, condoms or sexual abstinence), for at least the extension study period and one month after the end of the extension study.

  4. Stable therapy for at least one month, except in the case of patients under treatment with putative disease modifying agents (immunosupressants like cyclophosphamide, or azathioprine) that will need at least three months of stable therapy, without the expectation of treatment modifications during the trial period..
  5. Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed

Exclusion Criteria:

  1. Other skin diseases affecting the treatment area which could have been diagnosed during the ISD002-P144-07 study.
  2. Woman became pregnant during the ISD002-P144-07 study.
  3. Any new diagnosis since the ISD002-P144-07 study which includes: systemic sclerosis sine scleroderma, localized escleroderma, eosinophilic fascitis, or eosinophilia myalgia syndrome; any other definable connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, polymyositis, or dermatomyositis; clinically significant overlap condition; significant existing internal organ damage as defined in the guidelines for clinical trials in systemic sclerosis; history of skin cancer; other skin diseases affecting the treatment area.
  4. Substantial history of environmental exposure to tainted rapeseed oil, vinyl chloride, L- tryptophan, bleomycin, trichoroethylene, or silica; PUVA therapy within 1 month of study drug initiation; concurrent interventional therapy that might independently influence outcome of trial, such as D-penicillamine, cyclosporine, methotrexate, interferon-γ or photopheresis; topical corticosteroids treatment affecting the selected area; cosmetics over the treatment area.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00781053

Contacts
Contact: Raul Insa, MD, PhD 34932402020 ext 1134 raul.insa@isdin.com
Contact: Elena M Vernet, MD, PhD 34932402020 ext 1134 elena.vernet@isdin.com

Locations
Germany
Herz- und Rheumazentrum Kerckhoff-Klinik Not yet recruiting
Bad Hauheim, Germany, 61231
Contact: Ulf Müller-Ladner, PhD     06032 996 2101     u.mueller-ladner@kerxhhoff-klinik.de    
Contact: Tim Schmeiser, MD     06032 996 2101     t.schmeiser@kerckhoff-klinik.de    
Principal Investigator: Ulf Müller-Ladner, Phd            
Allergie-Centrum-Charité, Abteilung für Not yet recruiting
Berlin, Germany, 10117
Contact: Margarita Worm, PhD     030-450 518 105     margitta.worm@charite.de    
Contact: Claudia Rasche, MD     030-450 618 305     claudia.rasche@charite.de    
Principal Investigator: Margitta Worm, PhD            
Klinikum der Johan Wolfgang Goethe-Universitat Not yet recruiting
Frankfurt, Germany, 60590
Contact: Frank Behrens, PhD     069 6301 6109     frank.behrens@kgu.de    
Contact: Andrea Himsel, MD     069 6301 7312     andrea.himsel@kgu.de    
Sub-Investigator: Andrea Himsel, MD            
Klinik und Poliklinik für Dermatologie und Vererologie Not yet recruiting
Köln, Germany, 50937
Contact: Thomas M Krieg, PhD     0221 478 4500     thomas.krieg@uni-koeln.de    
Contact: Nicolas Hunzelmann, MD     0221 478 4517     nico.hunzelmann@koeln.de    
Sub-Investigator: Nicolas Hunzelmann, PhD            
Hungary
Immunologiai es Reumatologiai Klinika Not yet recruiting
Pécs, Hungary, H-7621
Contact: Czirjak Laszlo, PhD     0036 72 507 300 ext 7311     laszlo.czirjak@aok.pte.hu    
Contact: Kumanovics Gábor, MD     0036 72 507 300 ext 7122     gabor.kumanovics@aok.pte.hu    
Principal Investigator: Czirjak Laszlo, PhD            
Poland
Centrum Mirada Not yet recruiting
Bialystok, Poland, 15-297
Contact: Stanislaw Sierakowski, PhD     48-85 746 84 82     stanislawsierakowski@hotmail.com    
Contact: Elzbiela Muklewicz, MD     48-604937707     muckla@op.pl    
Principal Investigator: Stanislaw Sierakowski, PhD            
Samodzielny Publiczny Szpital Kliniczny Not yet recruiting
Katowice, Poland
Contact: Eugeniusz Kucharz, PhD     48-32 359 82 90     ekucharz@slam.katowice.pl    
Contact: Anna Kotulska, MD     48-32 359 82 90     akotulska@poczta.onet.pl    
Principal Investigator: Eugeniusz Kuchark, PhD            
Katedra i Klinika Raumatologizno Not yet recruiting
Poznan, Poland, 61-545
Contact: Mariusz Puszczewicz, PhD     48-603661016     pusczewicz@hotmail.com    
Contact: Aleksandra Kolczewska, MD     48-603661016     kolczewska1@hotmail.com    
Principal Investigator: Mariusz Puszczewicz, PhD            
Gabinet Lekarski Internistyczno- Reumatologiezny Not yet recruiting
Wroclaw, Poland, 53-137
Contact: Jacek Szechinski, PhD     48713602162     sekreum@reum.am.wroc.pl    
Contact: piotr Wiland, MD     48713602162     pwiland@provider.pl    
Principal Investigator: Jacek Szechinski, PhD            
Klinika Ftizjopneumonologii SAM Not yet recruiting
Zabrze, Poland, 41-803
Contact: Jerzy Kozielski, PhD     48- 32 27 56 64     jerzy.kozielski@neostrada.pl    
Contact: Dariusz Jastrzebski, MD     48- 32 27 56 64     darekdr@poczta.onet.pl    
Principal Investigator: Jerzy Kozielski, PhD            
Spain
Hospital Clinic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Contact: Carmen Herrero, PhD     34 93 227 54 00 ext 2422     CHERRERO@clinic.ub.es    
Principal Investigator: Carmen Herrerp, PhD            
Hospital 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Jose L Pablos, MD     34 91 390 85 98     jpablos@h12o.es    
Contact: Patricia Carreira, MD     34 91 390 85 98     carreira@h12o.es    
Sub-Investigator: Patricia Carreira, MD, PhD            
Clinica de Navarra Recruiting
Pamplona, Spain, 31008
Contact: Pedro Redondo, MD, PhD     34 948 25 54 00 ext 4312     predondo@unav.es    
Contact: Maider Pretel, MD,PhD     34 948 25 54 00 ext 4322     mpretel@unav.es    
Principal Investigator: Pedro Redondo, Phd            
United Kingdom
Chapel Allerton Hospital Active, not recruiting
Leeds, United Kingdom, NW3 2QG
Royal Free Hospital Recruiting
London, United Kingdom, Nw3 2QG
Contact: Christopher Denton, PhD     0207 830 2284     c.denton@medsch.ucl.ac.uk    
Contact: Rachel Ochiel, Nurse     0207 317 7544     rachel.Ochiel@royalree.nhs.uk    
Principal Investigator: Christopher Denton, PhD            
Sponsors and Collaborators
ISDIN
DigNA Biotech
Investigators
Study Chair: Marco Matucci, MD, PhD University of Florence
  More Information

ISDIN exists to take care of the skin with reliable and scientifically tested products.  This link exits the ClinicalTrials.gov site

Responsible Party: ISDIN ( ISDIN )
Study ID Numbers: ISD003-P144-08, 2008-001265-28
Study First Received: October 24, 2008
Last Updated: October 27, 2008
ClinicalTrials.gov Identifier: NCT00781053  
Health Authority: United Kingdom: National Health Service;   Spain: Ministry of Health and Consumption;   Germany: Federal Institute for Drugs and Medical Devices;   Hungary: National Institute of Pharmacy;   Poland: Ministry of Scientific Research and Information Technology

Keywords provided by ISDIN:
skin fibrosis
systemic scleroderma
systemic sclerosis
p144
orphan drug

Study placed in the following topic categories:
Skin Diseases
Fibrosis
Connective Tissue Diseases
Sclerosis
Scleroderma, Systemic

Additional relevant MeSH terms:
Pathologic Processes

ClinicalTrials.gov processed this record on January 16, 2009