Institutional Review Board, Hospital for Special Surgery
October 04, 2012
The safety of study participants is our top priority. The trial is approved and periodically reviewed by an Institutional Review Board (IRB), which includes doctors, administrators, ethicists, and members of the general public. The safety of clinical trials is reviewed by the U.S. Food and Drug Administration.
Before enrolling in a clinical trial, the investigator will explain the purpose of the trial, its expected benefits, any possible risks or side effects, and what your role will be. This is the time to ask questions! If you want to join the trial, you must sign the informed consent documents. You can leave a clinical trial at any time without penalty.
For further information, see Understanding Clinical Trials.
Jessica K. Gordon, MD
Lindsay Lally, MD
Steven Benkert, R. PhD.
Uzunma Udeh, BA
Nina Paddu, BA
Giant cell arteritis (GCA) and Takayasus arteritis (TAK) are granulomatous vasculitic diseases that share similar clinical, histologic, and immunopathogenic features. Involvement of the aorta and its main branches occurs in both diseases where it causes disability, morbidity, and mortality. Although glucocorticoids (GC) provide symptomatic improvement in GCA and TAK, they are toxic and do not prevent disease recurrence. Studies of arterial tissue support that GCA and TAK are antigen-driven diseases in which activated T cells play a critical role in pathogenesis.
Abatacept (CTLA4-Ig) is a novel agent that modulates the costimulation signal required for antigen-specific T cell activation. The actions of abatacept make this an appealing and innovative therapy to investigate in GCA and TAK, diseases for which there is a great need to identify better treatments.
A total of 33 subjects with GCA and 33 subjects with TAK will be treated in this study. Subjects must meet all of the following criteria to be eligible for enrollment:
1. A diagnosis of GCA or TAK
Diagnostic criteria for GCA
A subject will be said to have GCA by meeting 3 of 5 of the following modified ACR criteria for the classification of GCA in which 1 of the 3 must consist of criteria 4 or 5:
• Age at disease onset > 50 years.
• New onset or new type of localized pain in the head.
• ESR of > 40 mm in the first hour by the Westergren method.
• Temporal artery abnormality (i.e., temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries).
• Temporal artery or large vessel biopsy showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cell or characteristic changes of large vessel stenosis or aneurysm by arteriography
Diagnostic criteria for TAK
A subject will be said to have TAK defined by: Arteriographic abnormalities compatible with TAK (includes conventional dye angiography or MR angiography or CT angiography), plus at least one of the following:
• Age at disease onset <50 years
• Claudication of extremities
• Decreased brachial artery pulse (one or both arteries)
• Blood pressure difference of >10mm Hg between the arms
• Bruit over subclavian arteries or aorta
2. GCA or TAK with evidence of active disease (defined below) present within the past 2 months
3. Age of 18 years or older
4. They must be willing and able to comply with treatment and follow-up procedures
5. Both women and men who are of child-bearing potential must be willing to use an effective means of birth control while receiving treatment through this study. Effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or hormonal contraception.
6. They must be willing and able to provide written informed consent.
1. Evidence of active infection (includes chronic infection).
2. Subjects who are pregnant or who are nursing infants.
3. Infection with human immunodeficiency virus (HIV), hepatitis C, or a positive hepatitis B surface antigen.
4. Inability to comply with study guidelines.
5. Inability to provide informed consent.
6. Cytopenia: platelet count <80,000/mm3, absolute neutrophil <1500/mm3, hematocrit < 20%
7. Renal insufficiency defined by a serum creatinine of greater than or equal to 3.0 mg/dL or creatinine clearance of less than or equal to 20 ml/min.
8. Other uncontrolled disease (co-morbidity), including drug or alcohol abuse, that, in the investigator#s opinion, that could prevent a subject from fulfilling the study requirements or that would increase the risk of study procedures
9. History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin, or solid tumors treated with curative therapy and disease free for at least 5 years.
10. Receipt of an investigational agent or device within 30 days prior to enrollment
11. A live vaccination fewer than 4 weeks before enrollment
12. Presence of a positive tuberculin skin test with induration of > 5mm
13. Radiographic evidence suggestive of tuberculosis.
14. Poor tolerability of venipuncture or lack of adequate venous access for intravenous abatacept administration and blood sampling during the study period
15. Past treatment with rituximab within the past 12 months, or past treatment with rituximab more than 12 months ago where the B lymphocyte count has not returned to normal
16. Patients who have received infliximab within the past 49 days, adalimumab within the past 28 days, or etanercept within the past 21 days
17. Presence of any of the following disease processes:
• Microscopic polyangiitis
• Churg Strauss syndrome
• Polyarteritis nodosa
• Cogan's syndrome
• Behcet;s disease
• Kawasaki's disease
• Tuberculosis or atypical mycobacterial infections
• Deep fungal infections
• Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics vasculitis
• Cryoglobulinemic vasculitis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Mixed connective tissue disease or any overlap autoimmune syndrome
Uzunma Udeh, BA