Clinical trial NCT00442611: A Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Diffuse Systemic Sclerosis (Scleroderma)
Official title: A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Scleroderma, Diffuse
Scleroderma, Systemic
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2007-03-02
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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\&#xA;

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

Primary outcomes:
measure: Change in Modified Rodnan Skin Score
timeFrame: 6 months
Secondary outcomes:
measure: Oral Aperture at Baseline and Month 6
timeFrame: Baseline; Month 6
measure: Hand Extension at Baseline and Month 6
timeFrame: Baseline; Month 6
measure: Digital Ulcerations at Baseline and Month 6
timeFrame: Baseline; Month 6
measure: Change in Pulmonary Function Tests
timeFrame: 6 months
measure: Change in Scleroderma Health Assessment Questionnaire
timeFrame: 6 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Eliza Farmer Chakravarty
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.