A Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Diffuse Systemic Sclerosis (Scleroderma)

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00442611
First received: March 1, 2007
Last updated: July 20, 2011
Last verified: July 2011
  Purpose

Systemic sclerosis (scleroderma) is an autoimmune connective tissue disease that involves the skin and other internal organs for which there are few effective treatment options. We hypothesize that treatment with abatacept, a new therapy recently approved for the treatment of rheumatoid arthritis, may reduce the progression of skin thickening and fibrosis in people with scleroderma.


Condition Intervention Phase
Scleroderma, Diffuse
Scleroderma, Systemic
Drug: Abatacept
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Change in modified Rodnan Skin Score [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in oral aperture and hand extension [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in Pulmonary Function Tests [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Change in digital ulcerations [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Scleroderma Health Assessment Questionnaire [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in serum autoantibody profile [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Change in serum cytokine profile [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: November 2008
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abatacept
Study drug, Abatacept, will be administered in a double-blind fashion to the active arm of the study. It will be administered intravenously.
Drug: Abatacept
Active drug, abatacept, will be administered intravenously in a blinded fashion
Drug: Abatacept
Abatacept will be administered, dosed based upon weight, intravenously on days 1, 15, 30 and monthly thereafter for a total of 7 doses.
Placebo Comparator: IV fluid
The placebo arm will receive matched intravenous fluids.
Drug: Abatacept
Abatacept will be administered, dosed based upon weight, intravenously on days 1, 15, 30 and monthly thereafter for a total of 7 doses.

Detailed Description:

Systemic sclerosis is an autoimmune connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and internal organs, vascular damage, and autoantibody production. Although the disease is relatively rare, it is associated with considerable morbidity and mortality. There have been improvements in survival over the past few decades; however, this has been related to better management of vascular manifestations of disease including renal crisis, pulmonary hypertension, gastroesophageal reflux disease, and Raynaud's phenomenon. Clinical studies of disease modifying therapies for cutaneous disease to date have been relatively unsuccessful.

Although the etiology of the disease remains unknown, several observations support the role of activated T cells in both the blood and skin of affected patients. Abatacept, a recombinant fusion protein that blocks T cell activation, has recently been approved by the FDA for rheumatoid arthritis. We hypothesize that inhibition of T cell activation with abatacept may be efficacious in the treatment of patients with diffuse systemic sclerosis. This is a randomized, double-blinded, placebo-controlled clinical trial of abatacept versus placebo in patients with diffuse systemic sclerosis. Changes in validated measures of skin thickness and disease activity over 6-months of treatment will be compared between patients receiving abatacept and those receiving placebo. Patients will be randomized 2:1 to receive abatacept.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of diffuse systemic sclerosis
  • age 18 years or older
  • Adequate renal, pulmonary, and cardiovascular function
  • Willingness to use effective contraception for the duration of the study if subject is of childbearing potential


Exclusion Criteria:

  • Other connective tissues diseases or overlap syndromes including MCTD, SLE, RA, eosinophilic fasciitis, and limited systemic sclerosis or morphea
  • Use of disease modifying agents including methotrexate, cyclosporine,azathioprine, mycophenolate mofetil, minocycline, doxycycline, minocycline, thalidomide, penicillamine, tamoxifen, colchicine, or investigational agent within 90 days of screening visit
  • HIV, Hepatitis B or Hepatitis C infection
  • use of prednisone greater than 10mg daily for 28 days prior to screening visit
  • women who are breastfeeding or pregnant
  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: NCT00442611

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Bristol-Myers Squibb
Investigators
Principal Investigator: Eliza Farmer Chakravarty Stanford University
  More Information

No publications provided

Responsible Party: Eliza Chakravarty, Stanford University
ClinicalTrials.gov Identifier: NCT00442611     History of Changes
Other Study ID Numbers: 100 186
Study First Received: March 1, 2007
Last Updated: July 20, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Connective Tissue Diseases
Skin Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 01, 2014