Efficacy and Safety of Imatinib in Scleroderma

Scleroderma, Systemic Clinical Trial

— SCLEROGLIVEC  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00479934
• Other study ID #: CHUBX 2006/05
• Secondary ID: 2006/017
• Status: Completed
• Phase: Phase 2
• First received: May 29, 2007
• Last updated: March 3, 2011
• Start date: December 2007
• Est. completion date: December 2010

Study information

• Verified date: March 2011
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Localized
• Scleroderma, Systemic

Intervention

Drug:
• imatinib mesylate
6 month treatment with 400mg/day (per os)

Locations

Country	Name	City	State
France	Service de Dermatologie et services de médecine interne et vasculaire - Hôpital St André - CHU de Bordeaux	Bordeaux
France	Service de Rhumatologie, Hôpital Pellegrin-Tondu CHU de Bordeaux	Bordeaux
France	Service de Dermatologie - CHG Libourne	Libourne
France	Service de dermatologie - CHU de Limoges	Limoges
France	Service de Médecin interne - Hôpital central	Nancy
France	Service de Médecine interne - Hôpital Saint Louis	Paris
France	Service de Dermatologie - CHG Périgueux	Perigueux
France	Service de Dermatologie - service de médecine interne et vasculaire - hopital haut Lévêque - av.de magellan	Pessac
France	Service de Rhumatologie - CHU de Strasbourg	Strasbourg
France	Service de Dermatologie - CHU de Toulouse - Hopital Purpan	Toulouse
France	Service de Médecine interne - CHU de Tours	Tours
France	Néphrologie et Médecine interne - CH de Valenciennes	Valenciennes

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Bordeaux	Ministry of Health, France, Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		6 month	No
Secondary	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.		1, 3 and 12 month	No
Secondary	Assess skin thickness at inclusion and at 6 months using skin biopsies		6 month	No
Secondary	Assessment of quality of life using DLQI (Dermatology Quality of Life Index) and HAQ (Health Assessment Questionnaire).		At 1, 3, 6 month and 1 year,	No
Secondary	Assess tolerance of treatment (clinical and laboratory monitoring of side effects)		All along the trial	Yes
Secondary	Assess effects of treatment on non cutaneous symptoms in systemic sclerosis patients		All along the trial	Yes