Efficacy and Safety of Imatinib in Scleroderma

NCT00479934 | Completed Phase 2 DMC

• 2 other identifiers: CHUBX 2006/052006/017
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 12

Brief 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.

Conditions

Scleroderma, Localized; Scleroderma, Systemic

Keywords

scleroderma; imatinib; PDGFR; Rodnan

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• 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

• Assess skin thickness at inclusion and at 6 months using skin biopsies

  6 month

• 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,

• Assess tolerance of treatment (clinical and laboratory monitoring of side effects)

  All along the trial

• Assess effects of treatment on non cutaneous symptoms in systemic sclerosis patients

  All along the trial

Study Arms (2)

1

EXPERIMENTAL

6 month treatment with Imtinib 400mg/day

Drug: imatinib mesylate

2

PLACEBO COMPARATOR

6 month treatment with Placebo 400mg/day

Drug: imatinib mesylate

Interventions

imatinib mesylate DRUG

6 month treatment with 400mg/day (per os)

1; 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• More than 18 years old
• Documented diagnostic of scleroderma (systemic or cutaneous)
• Severe cutaneous sclerodermia or systemic sclerodermia with m-Rodnan score \> 20/51
• 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

You may not qualify if:

• 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
• Non controlled chronic illness (diabetes, chronic kidney failure, chronic hepatitis, HIV infection),
• 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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead
• Ministry of Health, France: collaborator
• Novartis: collaborator

Study Sites (12)

Service de Dermatologie et services de médecine interne et vasculaire - Hôpital St André - CHU de Bordeaux

Bordeaux, 33076, France

Location

Service de Rhumatologie, Hôpital Pellegrin-Tondu CHU de Bordeaux

Bordeaux, 33076, France

Location

Service de Dermatologie - CHG Libourne

Libourne, 33500, France

Location

Service de dermatologie - CHU de Limoges

Limoges, 87042, France

Location

Service de Médecin interne - Hôpital central

Nancy, 54035, France

Location

Service de Médecine interne - Hôpital Saint Louis

Paris, 75475, France

Location

Service de Dermatologie - service de médecine interne et vasculaire - hopital haut Lévêque - av.de magellan

Pessac, 33604, France

Location

Service de Dermatologie - CHG Périgueux

Périgueux, 24000, France

Location

Service de Rhumatologie - CHU de Strasbourg

Strasbourg, 67098, France

Location

Service de Dermatologie - CHU de Toulouse - Hopital Purpan

Toulouse, 31059 Toulouse Cedex, France

Location

Service de Médecine interne - CHU de Tours

Tours, 37044, France

Location

Néphrologie et Médecine interne - CH de Valenciennes

Valenciennes, 59322, France

Location

MeSH Terms

Conditions

Scleroderma, Localized; Scleroderma, Systemic; Scleroderma, Diffuse

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Alain TAIEB, Pr.

  University Hospital, Bordeaux, France

  STUDY DIRECTOR

• Geneviève CHENE, Pr

  University Hospital, Bordeaux, France

  STUDY CHAIR

• Alian TAIEB, Pr.

  University Hospital, Bordeaux, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 29, 2007
• First Posted: May 30, 2007
• Study Start: December 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: December 1, 2010
• Last Updated: March 4, 2011

Record last verified: 2011-03

Locations

FR (12)