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

Condition(s) targeted: Scleroderma, Diffuse; Scleroderma, Systemic

Intervention: Abatacept (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Stanford University

Official(s) and/or principal investigator(s):
Eliza Farmer Chakravarty, Principal Investigator, Affiliation: Stanford University

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.

Official title: A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Change in modified Rodnan Skin Score

Secondary outcome:

Change in oral aperture and hand extension

Change in Pulmonary Function Tests

Change in digital ulcerations

Scleroderma Health Assessment Questionnaire

Change in serum autoantibody profile

Change in serum cytokine profile

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Stanford University School of Medicine, Stanford, California 94305, United States; Recruiting
Eliza Chakravarty, MD, Phone: 650-725-5070, Email: echakravarty@stanford.edu
Jennifer Hillygus, Phone: (650) 723-7416, Email: jhillygu@stanford.edu
Eliza Farmer Chakravarty, Principal Investigator
Lorinda S Chung, Sub-Investigator
David Franklin Fiorentino, Sub-Investigator

Last updated: December 1, 2008