Skin FibrosisPhase 2NCT00574613
Efficacy and Safety Study of p144 to Treat Skin Fibrosis in Systemic Sclerosis
A Phase 2 study testing P144 in people with Skin Fibrosis, run by ISDIN at 17 sites in 6 countries.
Trial 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… 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
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 56 participants
- Where
- 17 sitesin 6 countries
- Study dates
- Sep 2007to Sep 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
- 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.
Who cannot join
- 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.
Show all 20Show fewer
- 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.
- Reasonable expectation that the subject will not be able to satisfactorily complete the study:
- History of or current psychiatric illness that would interfere with the subject's ability to comply with protocol requirements or give informed consent.
- History of alcohol or drug abuse that would interfere with the subject's ability to comply with protocol requirements.
- Receipt of any investigational drug within three months of screening visit.
- Documented noncompliance.
Trial locations and contacts
17 sites in 6 countries.
17 sites in 6 countries
Poland5 sites
Centrum Miriada
Bialystok, Bialystok, 15-297
Katedra i Klinika Chorób Wewnętrznych i Reumatologii
Katowice, Katowice, 40-635
Katedra i Klinika Reumatologiczno
Poznan, Poznan, 61-545
Gabinet Lekarski Internistyczno-Reumatologiczny
Wroclaw, Wroclaw, 53-342
Klinika Ftizjopneumonologii SAM
Zabrze, Zabrze, 41-803
Germany4 sites
Kerckhoff Klinik
Bad Nauheim, Hesse, 61231
Charité-Universitätsmedizin Berlin
Berlin, State of Berlin, 10117
Universität Köln
Cologne, Köln, 50931
Klinikum der Johann Wolfgang Goethe-Universität
Frankfurt, Frankfurt, 60590
Spain3 sites
Hospital Clínic
Barcelona, Barcelona, 08036
Hospital 12 de Octubre
Madrid, Madrid, 28041
Clínica Universitaria de Navarra
Pamplona, Pamplona, 31008
United Kingdom3 sites
Chapel Allerton Hospital
Leeds, Leeds, LS7 4SA
University Hospital Aintree
Liverpool, L9 7AL
Royal Free Hospital
London, London, NW3 2QG
Hungary1 site
Magyarorszagi Irgalmasrend es Pécsi Tudomanyegyetem
Pécs, Pécs, H-7621
About this study
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
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.
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-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.
- Conditions
- Skin Fibrosis
- Being tested
- P144, placebo
- Keywords
- Skin fibrosis, systemic scleroderma, systemic sclerosis, P144, orphan drug, soluble collagen, durometer, skin fibrosis in systemic sclerosis
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P144Drug
Cream 0,3 ml once a day (3 months)
placeboDrug
Cream 0,3 ml once a day (3 months)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: P144 |
| 2 | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage of reduction in the soluble collagen content and skin hardness after three months relative to baseline.
Measured: 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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2007 (estimated)
- Study startSep 2007
- Primary completionNov 2009
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- ISDIN
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Digna Biotech S.L.
- Investigators
- Marco Matucci, MD, Study chairThomas Krieg, MD, Principal investigatorUlf Müller-Ladner, MD, Principal investigatorLászló Czirják, MD, Principal investigatorChristopher Denton, MD, Principal investigatorJosé Luis Pablos, MD, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00574613
- Sponsor's protocol ID
- ISD002-P144-07
- Other IDs
- 2007-002015-38
- Status last verified
- Feb 2013
- First submitted
- 13 Dec 2007
- Last updated
- 11 Feb 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 15158741White 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.
PubMed 7880189Querfeld 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.
PubMed 10468187Kissin 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.
PubMed 16874783
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
- 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
- ClinicalTrials.gov ID
- NCT00574613
- Acronym / sponsor ID
- ISD002-P144-07
- Conditions
- Skin Fibrosis
- Keywords
- Skin fibrosis, systemic scleroderma, systemic sclerosis, P144, orphan drug, soluble collagen, durometer, skin fibrosis in systemic sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- ISDINIndustry (pharma, biotech, devices)
- Collaborators
- Digna Biotech S.L.
- Study start
- Sep 2007
- Primary completion
- Nov 2009 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 17 Dec 2007 (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 (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.
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-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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: P144 |
| 2 | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (20 listed)
- Patients diagnosed of:
- 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.
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 |
|---|---|---|
| P144Cream 0,3 ml once a day (3 months) | Drug | 1 |
| placeboCream 0,3 ml once a day (3 months) | Drug | 2 |
Primary outcome
The percentage of reduction in the soluble collagen content and skin hardness after three months relative to baseline.
Time frame: Three months
1 secondary outcome
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
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.
- Background: PubMed 15158741Denton 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.
- Background: PubMed 7880189White 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.
- Background: PubMed 10468187Querfeld 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.
- Background: PubMed 16874783Kissin 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.
- Asociación española de esclerodermiaLink provided by the sponsor.
Related trials for Skin Fibrosis
Not yet recruitingPhase 2
Hyaluronidase Injections for Sclerodactyly in Patients With Scleroderma
Scleroderma, Sclerodactyly
RecruitingObservational study
Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
Hermansky-Pudlak Syndrome (HPS)
RecruitingPhase 2
Tirzepatide for Treatment of CCCA
Central Centrifugal Cicatricial Alopecia (CCCA)
Not yet recruiting
Prospective Evaluation of Recombinant Pbserum Plus® and Pbserum HA 2.0® in Aesthetic and Regenerative Bioremodeling
Skin Laxity, Localized Adiposity
Active, not recruiting
Clinical Study to Evaluate the Safety and Efficacy of Candela Technology
Hair Reduction, Tattoo Removal
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 study chair
Thomas Krieg, MD principal investigator
Ulf Müller-Ladner, MD principal investigator
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 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 7 inclusion and 20 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. Some participants in this study may receive a placebo. 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?
The percentage of reduction in the soluble collagen content and skin hardness after three months relative to baseline. (time frame: Three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00574613, which also lists 4 linked publications.
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.