Imatinib in Systemic Sclerosis

NCT ID: NCT00506831

Last Updated: 2018-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2010-09-30

Brief Summary

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs and widespread vasculopathy. Patients with SSc are classified according to the extent of cutaneous sclerosis: patients with limited SSc have skin thickening of the face, neck, and distal extremities, while those with diffuse SSc have involvement of the trunk, abdomen, and proximal extremities as well. The disease course varies depending on the subtype of SSc. However, common features that result in significant morbidity and mortality, in addition to cutaneous fibrosis, include Raynaud's phenomenon and digital ulcerations, interstitial lung disease (ILD), and pulmonary arterial hypertension (PAH). Current therapeutic options for patients with SSc and these clinical manifestations have shown limited efficacy.

Imatinib antagonizes specific tyrosine kinases that mediate fibrotic pathways involved in the pathogenesis of SSc, including c-Abl, a downstream mediator of transforming growth factor (TGF)-beta, and platelet derived growth factor (PDGF) receptors. The efficacy of imatinib has also been reported in the treatment of patients with refractory idiopathic PAH through its effects on vascular remodeling. Based on the mechanism of action and preliminary patient data, we hypothesize that imatinib may be effective in the treatment of the fibrotic and vasculopathic features of patients with SSc. This is an open label pilot study to evaluate the safety and efficacy of imatinib in patients with progressive SSc refractory to other treatment(s). Validated measures of skin thickness and disease activity will be determined over 6-months of therapy and compared with baseline measures.

Conditions

Scleroderma, Systemic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imatinib mesylate

100 mg daily and increase by 100mg daily every 2 weeks to a maximum of 400 mg daily as tolerated

Group Type: EXPERIMENTAL

Imatinib mesylate

Intervention Type: DRUG

100 mg orally daily increased by 100 mg/day every 2 weeks to maximum of 400 mg daily as tolerated. Treatment for 6 months total.

Interventions

Imatinib mesylate

100 mg orally daily increased by 100 mg/day every 2 weeks to maximum of 400 mg daily as tolerated. Treatment for 6 months total.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Adults with refractory diffuse or limited SSc and any or all of the following: Progressive cutaneous fibrosis, Interstitial lung disease, Pulmonary arterial hypertension, Digital ulcerations.

Exclusion Criteria

Uncontrolled congestive heart failure, hypertension, or coronary artery disease.

HIV, hepatitis B, and/or hepatitis C infection. Serious infection within the past month. Significant hematologic, renal, or hepatic abnormalities. Concurrent use of intravenous immunoglobulin or cyclophosphamide within 4 weeks of the first treatment dose.

Concurrent use of a biologic agent (ie. etanercept, infliximab, adalimumab, abatacept) within 8 weeks of the first treatment dose (6 months for rituximab).

Women who are pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Lorinda S Chung

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lorinda S Chung

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

Whitfield ML, Finlay DR, Murray JI, Troyanskaya OG, Chi JT, Pergamenschikov A, McCalmont TH, Brown PO, Botstein D, Connolly MK. Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12319-24. doi: 10.1073/pnas.1635114100. Epub 2003 Oct 6.

Reference Type: BACKGROUND

PMID: 14530402 (View on PubMed)

Chung L, Fiorentino DF, Benbarak MJ, Adler AS, Mariano MM, Paniagua RT, Milano A, Connolly MK, Ratiner BD, Wiskocil RL, Whitfield ML, Chang HY, Robinson WH. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum. 2009 Feb;60(2):584-91. doi: 10.1002/art.24221.

Reference Type: RESULT

PMID: 19180499 (View on PubMed)

Other Identifiers

9598

Identifier Type: -

Identifier Source: secondary_id

9598

Identifier Type: -

Identifier Source: org_study_id