Efficacy and Safety of Imatinib in Scleroderma (SCLEROGLIVEC)

University Hospital of Bordeaux

Status and phase

Completed

Phase 2

Conditions

Scleroderma, Systemic

Scleroderma, Localized

Treatments

Drug: imatinib mesylate

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00479934

2006/017

CHUBX 2006/05

Details and patient eligibility

About

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.

Full 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.

Enrollment

28 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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