Imatinib in Systemic Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Lorinda S Chung, Stanford University
ClinicalTrials.gov Identifier:
NCT00506831
First received: July 24, 2007
Last updated: July 10, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Scleroderma, Systemic
Drug: Imatinib mesylate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Imatinib in the Treatment of Refractory Systemic Sclerosis

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Percent Change in Modified Rodnan Skin Score at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]
    Modified Rodnan skin score (mRSS) on scale of 0 (no skin disease) to 51 severe skin disease. %change in mRSS=(score at 6 months - baseline score)/baseline score. Negative values indicate improvement in skin disease. Clinical important improvement defined as > 25% improvement.


Secondary Outcome Measures:
  • Change in Pulmonary Function Tests at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]
  • Change in Digital Ulcerations at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]
  • Change in Scleroderma Health Assessment Questionnaire at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]
  • Change in Dermal Thickness and Collagen Separation on Cutaneous Histopathology at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]
  • Change in Serum Cytokine Profile at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]
  • Change in High Throughput Gene Expression Analysis at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]
  • Change in Serum Autoantibody Profile at 6 Months Compared to Baseline [ Time Frame: 6 months compared to baseline ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: July 2007
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imatinib mesylate
100 mg daily and increase by 100mg daily every 2 weeks to a maximum of 400 mg daily as tolerated
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  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: NCT00506831

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Lorinda S Chung Stanford University
  More Information

No publications provided

Responsible Party: Lorinda S Chung, Assistant Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT00506831     History of Changes
Other Study ID Numbers: 9598, 9598
Study First Received: July 24, 2007
Results First Received: June 6, 2012
Last Updated: July 10, 2012
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 29, 2014