Skin FibrosisPhase 2NCT00781053
Open Label Extension (OLE) for the Patients Treated in the ISD002-P144-07 Study
A Phase 2 study testing P144 cream in people with Skin Fibrosis, run by ISDIN at 17 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Skin Fibrosis
- What is being tested?
- P144 cream
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 17 sitesin 6 countries
- Study dates
- Jul 2008to Dec 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previous participation and finalization of treatment period of the ISD002-P144-07 study without clinical relevant safety issues medically evaluated by the investigator.
- 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.
- 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.
- 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..
- Capable of understanding and willing to provide signed and dated written voluntary informed consent before any protocol specific procedures are performed
Who cannot join
- Other skin diseases affecting the treatment area which could have been diagnosed during the ISD002-P144-07 study.
- Woman became pregnant during the ISD002-P144-07 study.
- 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.
- 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.
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
Poland5 sites
Centrum Mirada
Bialystok, Bialystok, 15-297
Samodzielny Publiczny Szpital Kliniczny
Katowice, Katowice
Katedra i Klinika Raumatologizno
Poznan, Poznan, 61-545
Gabinet Lekarski Internistyczno- Reumatologiezny
Wroclaw, Wroclaw, 53-137
Klinika Ftizjopneumonologii SAM
Zabrze, Zabrze, 41-803
Germany4 sites
Herz- und Rheumazentrum Kerckhoff-Klinik
Bad Hauheim, Bad Hauheim, 61231
Allergie-Centrum-Charité, Abteilung für
Berlin, State of Berlin, 10117
Klinik und Poliklinik für Dermatologie und Vererologie
Cologne, Köln, 50937
Klinikum der Johan Wolfgang Goethe-Universitat
Frankfurt, Frankfurt, 60590
Spain3 sites
Hospital Clinic i Provincial de Barcelona
Barcelona, Barcelona, 08036
Hospital 12 de Octubre
Madrid, Madrid, 28041
Clinica de Navarra
Pamplona, Pamplona, 31008
United Kingdom3 sites
Chapel Allerton Hospital
Leeds, Leeds, NW3 2QG
University Hospital Aintree
Liverpool, L9 7AL
Royal Free Hospital
London, London, Nw3 2QG
About this 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
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.
Read the 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.
- Conditions
- Skin Fibrosis
- Being tested
- P144 cream
- Keywords
- skin fibrosis, systemic scleroderma, systemic sclerosis, p144, orphan drug
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P144 creamDrug
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
| Study group | Role | What they receive |
|---|---|---|
| P144 cream | Experimental | P144 cream 0.03% will be used once a day during the whole extension period of 6 months. Receives: Drug: P144 cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the long-term safety of digna P144 cream topically administered in skin manifestations of systemic sclerosis patients.
Measured: 6 months
Secondary outcomes (1)
Quality o life assessment, skin induration and hardness. In a subgroup of patients pharmacokinetic and elasticity will be measured.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2008 (estimated)
- Study startJul 2008
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Skin FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- ISDIN
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Digna Biotech S.L.
- Investigators
- Marco Matucci, MD, PhD, Study chair, University of Florence
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00781053
- Sponsor's protocol ID
- ISD003-P144-08
- Other IDs
- 2008-001265-28, 2008
- Status last verified
- Feb 2013
- First submitted
- 24 Oct 2008
- Last updated
- 11 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00781053
- Acronym / sponsor ID
- ISD003-P144-08
- Conditions
- Skin Fibrosis
- Keywords
- skin fibrosis, systemic scleroderma, systemic sclerosis, p144, orphan drug
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- ISDINIndustry (pharma, biotech, devices)
- Collaborators
- Digna Biotech S.L.
- Study start
- Jul 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 28 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| P144 cream | Experimental | Drug: P144 creamP144 cream 0.03% will be used once a day during the whole extension period of 6 months. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Previous participation and finalization of treatment period of the ISD002-P144-07 study without clinical relevant safety issues medically evaluated by the investigator.
- 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.
- 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.
- 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..
Key exclusion criteria (4 listed)
- Other skin diseases affecting the treatment area which could have been diagnosed during the ISD002-P144-07 study.
- Woman became pregnant during the ISD002-P144-07 study.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| P144 creamP144 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 | Drug | P144 cream |
Primary outcome
Assess the long-term safety of digna P144 cream topically administered in skin manifestations of systemic sclerosis patients.
Time frame: 6 months
1 secondary outcome
Quality o life assessment, skin induration and hardness. In a subgroup of patients pharmacokinetic and elasticity will be measured.
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2013.
- ISDIN exists to take care of the skin with reliable and scientifically tested products.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Matucci, MD, PhD study chair
University of Florence
17 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing P144 cream in people with Skin Fibrosis, run by ISDIN at 17 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in Poland, Germany, Spain, United Kingdom, Hungary and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the long-term safety of digna P144 cream topically administered in skin manifestations of systemic sclerosis patients. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2013.