Efficacy and Safety of Imatinib in Scleroderma - Full Text View

Purpose

In vitro studies have shown that imatinib 1mM inhibits strongly the growth of cutaneous fibroblasts. The hypothesis is that imatinib inhibits PDGFR which is known to be a potential target for the molecule, as recently also proposed after the discovery of autoantibodies activating the PDGF receptors. Recent data indicate that TGFb is also a potential target of imatinib. Cutaneous scleroderma is characterized by progressive cutaneous fibrosis caused by hyperactive dermal fibroblasts. Since no established treatment for skin sclerosis in scleroderma is currently available. This study will test the safety and efficacy of imatinib in the treatment of patients with scleroderma and severe cutaneous involvement.

Condition	Intervention	Phase
Scleroderma, Localized Scleroderma, Systemic	Drug: imatinib mesylate	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Phase II Randomized Double Blind Clinical Trial of'Imatinib Mesylate STI571 (Glivec®) Versus Placebo in Patients With Severe Cutaneous Scleroderma or Systemic Sclerosis With Severe Cutaneous Involvement.

Resource links provided by NLM:

Genetics Home Reference related topics: systemic scleroderma

MedlinePlus related topics: Scleroderma

Drug Information available for: Imatinib Imatinib mesylate

U.S. FDA Resources

Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:

Compare the efficacy of imatinib mesylate vs placebo based on the percent variation of modified Rodnan score (0-51) between inclusion and 6-month visits. [ Time Frame: 6 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Compare efficacy of imatinib mesylate vs placebo based on the percent variation of modified Rodnan score between the inclusion and the various time points of follow-up. [ Time Frame: 1, 3 and 12 month ] [ Designated as safety issue: No ]
Assess skin thickness at inclusion and at 6 months using skin biopsies [ Time Frame: 6 month ] [ Designated as safety issue: No ]
Assessment of quality of life using DLQI (Dermatology Quality of Life Index) and HAQ (Health Assessment Questionnaire). [ Time Frame: At 1, 3, 6 month and 1 year, ] [ Designated as safety issue: No ]
Assess tolerance of treatment (clinical and laboratory monitoring of side effects) [ Time Frame: All along the trial ] [ Designated as safety issue: Yes ]
Assess effects of treatment on non cutaneous symptoms in systemic sclerosis patients [ Time Frame: All along the trial ] [ Designated as safety issue: Yes ]

Enrollment:	28
Study Start Date:	December 2007
Study Completion Date:	December 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 6 month treatment with Imtinib 400mg/day	Drug: imatinib mesylate 6 month treatment with 400mg/day (per os)
Placebo Comparator: 2 6 month treatment with Placebo 400mg/day	Drug: imatinib mesylate 6 month treatment with 400mg/day (per os)

Detailed Description:

This study will test the efficacy and tolerance of patients with a high score of induration (modified Rodnan score > 20/54) Comparison : 34 patients with severe forms of cutaneous involvement will be evaluated in a double blind RCT comparing imatinib 400mg/j and placebo in a 6 month period. Efficacy will be assessed using a cutaneous induration scale and skin biopsy, and quality of life questionnaires.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

More than 18 years old
Documented diagnostic of scleroderma (systemic or cutaneous)
Severe cutaneous sclerodermia or systemic sclerodermia with m-Rodnan score > 20/51
Ejection fraction of more than 45 per cent at cardiac ultrasound pre-inclusion study
Woman with efficient contraceptive method during trail treatment and during 3 month after the end of trial treatment
All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the 7 days prior to enrolment
Affiliated or profit patient of a social security system
Signed informed consent

Exclusion Criteria:

new systemic treatment, potentially interfering with disease progression, beginning 3 months prior the start trial treatment
Patient with isolated cutaneous scleroderma treated with a drug potentially interfering with the course of the disease 4 weeks before starting the trial (Systemic corticosteroids, methotrexate, cyclophosphamide, bosentan)
Scleroderma " en coup de sabre "
Severe organ failure or anomaly of blood chemistry/hematology (bilirubin, SGOT, SGPT, creatinine > 1,5 ´ upper normal limit, polymorphonuclear granulocytes less than 1*10*9/l or platelets less than 50*10*9/l),
Ongoing cancer
Ejection fraction ≤ 45 per cent at cardiac ultrasound pre inclusion study
myocardial infarction of less than 6 mois at pre inclusion visit
Non controlled chronic illness (diabetes, chronic kidney failure, chronic hepatitis, HIV infection),
Major surgery less than two weeks before inclusion
Pregnancy or lactation
Absence of validated contraception in childbearing women.
Contraindication to imatinib mesylate treatment as specified in product specifications
Non observance anticipated and absence of informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00479934

Locations

France
Service de Dermatologie et services de médecine interne et vasculaire - Hôpital St André - CHU de Bordeaux
Bordeaux, France, 33076
Service de Rhumatologie, Hôpital Pellegrin-Tondu CHU de Bordeaux
Bordeaux, France, 33076
Service de Dermatologie - CHG Libourne
Libourne, France, 33500
Service de dermatologie - CHU de Limoges
Limoges, France, 87042
Service de Médecin interne - Hôpital central
Nancy, France, 54035
Service de Médecine interne - Hôpital Saint Louis
Paris, France, 75475
Service de Dermatologie - CHG Périgueux
Perigueux, France, 24000
Service de Dermatologie - service de médecine interne et vasculaire - hopital haut Lévêque - av.de magellan
Pessac, France, 33604
Service de Rhumatologie - CHU de Strasbourg
Strasbourg, France, 67098
Service de Dermatologie - CHU de Toulouse - Hopital Purpan
Toulouse, France, 31059 Toulouse Cedex
Service de Médecine interne - CHU de Tours
Tours, France, 37044
Néphrologie et Médecine interne - CH de Valenciennes
Valenciennes, France, 59322

Sponsors and Collaborators

University Hospital, Bordeaux

Ministry of Health, France

Novartis

Investigators

Study Director:	Alain TAIEB, Pr.	University Hospital, Bordeaux, France
Study Chair:	Geneviève CHENE, Pr	University Hospital, Bordeaux, France
Principal Investigator:	Alian TAIEB, Pr.	University Hospital, Bordeaux, France

More Information

No publications provided

Responsible Party:	Jean-Pierre LEROY / Clinical Research and Innovation Director, University Hospital, Bordeaux
ClinicalTrials.gov Identifier:	NCT00479934 History of Changes
Other Study ID Numbers:	CHUBX 2006/05, 2006/017
Study First Received:	May 29, 2007
Last Updated:	March 3, 2011
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:

scleroderma
imatinib
PDGFR
Rodnan

Additional relevant MeSH terms:

Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Connective Tissue Diseases
Skin Diseases
Imatinib

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013

Efficacy and Safety of Imatinib in Scleroderma (SCLEROGLIVEC)