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

NCT00574613 | Completed Phase 2

• 2 other identifiers: ISD002-P144-072007-002015-38
• Study Type: interventional
• Target: 56
• Locations: 6 countries
• Sites: 17

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 asses the efficacy and safety of topical application of P144 in the treatment of skin fibrosis in patients with systemic sclerosis.

Conditions

Skin Fibrosis

Keywords

Skin fibrosis; systemic scleroderma; systemic sclerosis; P144; orphan drug; soluble collagen; durometer; skin fibrosis in systemic sclerosis

Outcome Measures

Primary Outcomes (1)

• The percentage of reduction in the soluble collagen content and skin hardness after three months relative to baseline.

  Three months

Secondary Outcomes (1)

• 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.

  3 months

Study Arms (2)

1

EXPERIMENTAL

Drug: P144

2

PLACEBO COMPARATOR

Drug: placebo

Interventions

P144 DRUG

Cream 0,3 ml once a day (3 months)

1

placebo DRUG

Cream 0,3 ml once a day (3 months)

2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients male and female \>18 \< 65 years at time of consent.
• History of Systemic sclerosis (including diffuse scleroderma and limited scleroderma) for less than three years of evolution from the onset of cutaneous manifestations.
• Symmetric lesions in forearms. The extension of the selected symmetric lesions must be at least 15 cm2.
• Stable therapy for at least one month, except in the case of patients under treatment with putative disease modifying agents (immunosuppressants like cyclophosphamide, or azathioprine) that will need at least three months of stable therapy, without the expectation of treatment modifications during the trial period.
• Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed.
• 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 three consecutive months prior to the study, during the study and one month after the end of the study.
• For male subjects with partners of child bearing potential: use of appropriate contraceptive methods (vasectomy, condoms or sexual abstinence), for at least the study period and one month after the end of the study.

You may not qualify if:

• Patients diagnosed of:
• Systemic sclerosis sine scleroderma.
• Localized scleroderma.
• Eosinophilic fascitis, 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 (Kidney, Cardiovascular disease, Pulmonary disease, Gastrointestinal disease) as defined in "Guidelines for clinical trial in systemic sclerosis (scleroderma) " See appendix 1.
• History of skin cancer.
• Other skin diseases affecting the treatment area.
• Patients with substantial history of environmental exposure to tainted rapeseed oil, vinyl chloride, L- tryptophan, bleomycin, trichloroethylene, 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-α or photopheresis.
• Topical corticosteroids treatment affecting the selected area.
• Cosmetics over the treatment area.
• Pregnant or breast-feeding women.

Sponsors & Collaborators

• ISDIN: lead
• Digna Biotech S.L.: collaborator

Study Sites (17)

Klinikum der Johann Wolfgang Goethe-Universität

Frankfurt, Frankfurt, 60590, Germany

Location

Kerckhoff Klinik

Bad Nauheim, Hesse, 61231, Germany

Location

Universität Köln

Cologne, Köln, 50931, Germany

Location

Charité-Universitätsmedizin Berlin

Berlin, State of Berlin, 10117, Germany

Location

Magyarorszagi Irgalmasrend es Pécsi Tudomanyegyetem

Pécs, Pécs, H-7621, Hungary

Location

Azienda Ospedaliera Universitaria Careggi.

Florence, 50139, Italy

Location

Centrum Miriada

Bialystok, Bialystok, 15-297, Poland

Location

Katedra i Klinika Chorób Wewnętrznych i Reumatologii

Katowice, Katowice, 40-635, Poland

Location

Katedra i Klinika Reumatologiczno

Poznan, Poznan, 61-545, Poland

Location

Gabinet Lekarski Internistyczno-Reumatologiczny

Wroclaw, Wroclaw, 53-342, Poland

Location

Klinika Ftizjopneumonologii SAM

Zabrze, Zabrze, 41-803, Poland

Location

Hospital Clínic

Barcelona, Barcelona, 08036, Spain

Location

Hospital 12 de Octubre

Madrid, Madrid, 28041, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Pamplona, 31008, Spain

Location

Chapel Allerton Hospital

Leeds, Leeds, LS7 4SA, United Kingdom

Location

Royal Free Hospital

London, London, NW3 2QG, United Kingdom

Location

University Hospital Aintree

Liverpool, L9 7AL, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 15158741 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.

  PMID: 7880189 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.

  PMID: 10468187 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.

  PMID: 16874783 BACKGROUND

Related Links

• Asociación española de esclerodermia

MeSH Terms

Conditions

Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Marco Matucci, MD

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 13, 2007
• First Posted: December 17, 2007
• Study Start: September 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: September 1, 2010
• Last Updated: February 11, 2013

Record last verified: 2013-02

Locations

GB (3); ES (3); HU (1); IT (1); DE (4); PL (5)