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

NCT ID: NCT00442611

Last Updated: 2017-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2011-06-30

Brief Summary

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.

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.

The protocol was amended during the study and the outcome measures "Change in Serum Autoantibody Profile" and "Change in Serum Cytokine Profile" were changed to exploratory outcomes.

Conditions

Scleroderma, Diffuse; Scleroderma, Systemic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Abatacept

Abatacept (dosed based upon weight) administered intravenously (IV) on days 1, 15, 30 and monthly thereafter for a total of 7 doses.

Group Type: EXPERIMENTAL

Abatacept

Intervention Type: DRUG

IV fluid

Placebo to match abatacept (IV fluid) administered on days 1, 15, 30 and monthly thereafter for a total of 7 doses.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Abatacept

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility 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

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

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Lorinda S Chung

Principle Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eliza Farmer Chakravarty

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

Chakravarty EF, Martyanov V, Fiorentino D, Wood TA, Haddon DJ, Jarrell JA, Utz PJ, Genovese MC, Whitfield ML, Chung L. Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis. Arthritis Res Ther. 2015 Jun 13;17(1):159. doi: 10.1186/s13075-015-0669-3.

Reference Type: DERIVED

PMID: 26071192 (View on PubMed)

Other Identifiers

100 186

Identifier Type: -

Identifier Source: org_study_id