Efficacy and Safety of Imatinib in Scleroderma (SCLEROGLIVEC)

This study has been completed.
Ministry of Health, France
Information provided by:
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
First received: May 29, 2007
Last updated: March 3, 2011
Last verified: March 2011
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:

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.

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

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
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

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:

Additional relevant MeSH terms:
Scleroderma, Diffuse
Scleroderma, Localized
Scleroderma, Systemic
Connective Tissue Diseases
Skin Diseases
Imatinib Mesylate
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on May 26, 2016