Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu's Arteritis
Condition: Takayasu's Arteritis; Giant Cell Arteritis
MeSH terms: Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis; Takayasu Arteritis; Aortic Arch Syndromes
Intervention: Abatacept; Placebo
Intervention description: Participants will receive a fixed dose of abatacept, approximating 10mg per kilogram of body weight. The following dosing rules will be followed:
Participants weighing less than 60kg will receive 500mg of abatacept.
Participants weighing 60 to 100kg will receive 750mg of abatacept.
Participants weighing more than 100kg will receive 1000mg of abatacept.
Abatacept will be administered in a 30-minute intravenous infusion on Days 1, 15, 29 (Month 1) and at Month 2. In the absence of toxicity or relapse, participants will remain on abatacept at the same dosage until randomization at Month 3. After randomization, only Group A (giant cell arteritis) and Group C (Takayasu arteritis) participants will continue on abatacept.; Placebo abatacept infusions will be given monthly after random assignment at Month 3.
Intervention MeSH terms: Abatacept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 97.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: Vasculitis; Arteritis; Takayasu's; Temporal Arteritis; Abatacept

Summary:

      Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are diseases that cause swelling of
      the arteries in the head, neck, upper body, and arms. TAK specifically affects the aorta, the
      largest blood vessel in the body, and its branches. Therapies are available to improve the
      symptoms of GCA and TAK, but relapse often occurs, and better treatments are needed.
      Abatacept is a drug that interacts with certain cells in the body that are involved with GCA
      and TAK. This study will evaluate the effectiveness of abatacept in treating GCA and TAK and
      preventing disease relapse.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of GCA or TAK (defined below)

          -  History of active GCA or TAK within the past 2 months

          -  Age of 15 years or older

          -  Willing to use an effective means of birth control throughout the study

        Specific Inclusion Criteria for Participants with GCA:

          -  Participants must meet three of the following five criteria, including either
             Criterion 4 or 5:

               1. Age at disease onset was equal to or greater than 50 years

               2. Disease onset was recent or experiencing a new type of localized pain in the head

               3. Erythrocyte sedimentation rate greater than 40mm in the first hour, as determined
                  using the Westergren method

               4. Temporal artery abnormality (i.e., temporal artery tenderness to palpation or
                  decreased pulsation, unrelated to arteriosclerosis of cervical arteries)

               5. 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

        Specific Inclusion Criteria for Participants with TAK:

          -  Presence of abnormalities that are consistent with TAK identified using arteriography,
             plus at least one of the following criteria:

               1. Age at disease onset was less than 50 years

               2. Pain in the legs or arms

               3. Decreased brachial artery pulse (one or both arteries)

               4. Difference of more than 10mm Hg in blood pressure between the arms

               5. Bruit over subclavian arteries or aorta

        Exclusion Criteria:

          -  Evidence of active infection (including chronic infection)

          -  Pregnant or breastfeeding

          -  HIV infected, hepatitis C infected, or a positive hepatitis B surface antigen

          -  Inability to comply with study guidelines

          -  Inability to provide informed consent

          -  Cytopenia, as defined by a platelet count of less than 80,000/mm3, an absolute
             neutrophil count of less than 1,500/mm3, and hematocrit less than 20%

          -  Insufficient kidney function, as defined by a serum creatinine of more than 3 mg/dL or
             creatinine clearance of 20 ml/min or less

          -  Other uncontrolled disease that could prevent safe study completion

          -  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

          -  Receipt of an investigational agent or device within 30 days prior to study entry

          -  A live vaccination within 4 weeks prior to study entry

          -  Presence of a positive tuberculin skin test with induration of at least 5mm

          -  Radiographic evidence suggestive of tuberculosis

          -  Poor tolerability of blood draws or lack of adequate access to veins for medication
             administration and blood draws

          -  History of treatment with rituximab within 12 months prior to study entry or history
             of treatment with rituximab more than 12 months prior to study entry, where the B
             lymphocyte count has not returned to normal

          -  History of treatment with infliximab within the past 49 days, adalimumab within the
             past 28 days, or etanercept within the past 21 days.

          -  Presence of any of the following diseases or conditions:

               1. Microscopic polyangiitis

               2. Churg-Strauss syndrome

               3. Polyarteritis nodosa

               4. Cogan's syndrome

               5. Behcet disease

               6. Sarcoidosis

               7. Kawasaki disease

               8. Tuberculosis or atypical mycobacterial infection

               9. Deep fungal infection

              10. Lymphoma, lymphomatoid granulomatosis, or other type of malignancy that mimics
                  vasculitis

              11. Cryoglobulinemic vasculitis

              12. Systemic lupus erythematosus

              13. Rheumatoid arthritis

              14. Mixed connective tissue disease or any overlap autoimmune syndrome