Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu's Arteritis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Cleveland Clinic
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier:
NCT00556439
First received: November 9, 2007
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Takayasu's Arteritis
Giant Cell Arteritis
Drug: Abatacept
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Concurrent Pilot Studies in Giant Cell Arteritis and Takayasu's Arteritis to Examine the Safety, Efficacy, and Immunologic Effects of Abatacept (CTLA4-Ig) in Large Vessel Vasculitis

Resource links provided by NLM:


Further study details as provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):

Primary Outcome Measures:
  • Remission duration [ Time Frame: Months 0 to 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Drug toxicity [ Time Frame: Months 0 to 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 66
Study Start Date: December 2008
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
This is a randomized withdrawal design protocol. All participants will receive abatacept and prednisone (a glucocorticoid) for the first 3 months. Abatacept will be given intravenously on selected days. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Month 3, and finally further tapered until discontinuation is reached. At Month 3, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to abatacept at this point will be in Group A.
Drug: Abatacept

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 participants will continue on abatacept.

Other Name: Orencia
Placebo Comparator: B
This is a randomized withdrawal design protocol. All participants will receive abatacept and prednisone (a glucocorticoid) for the first 3 months. Abatacept will be given intravenously on selected days. Prednisone will be started at a dose of 40 to 60mg, then tapered to 20mg by Month 3, and finally further tapered until discontinuation is reached. At Month 3, participants who have achieved remission will be randomly assigned under double-blind conditions to receive monthly infusions of either abatacept or placebo. Participants who are assigned to placebo at this point will be in Group B.
Drug: Abatacept

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 participants will continue on abatacept.

Other Name: Orencia
Drug: Placebo
Placebo abatacept infusions will be given monthly after random assignment at Month 3.

Detailed Description:

GCA and TAK both cause inflammation in the lining of the arteries, which can interfere with the body's ability to carry oxygen to areas that need it. Symptoms of GCA include headaches, jaw pain, and blurred or double vision. Serious symptoms that occur less commonly are blindness and stroke. TAK symptoms include fever, fatigue, weight loss, arthritis, and non-specific aches and pains. There may also be tenderness near affected arteries. Researchers believe that GCA and TAK are diseases that are controlled by the body's immune system. Activated T-cells, specifically, are critical to the origin and development of these diseases. Abatacept is a medication that modulates the signal required for T-cell activation. This study will evaluate the safety and effectiveness of abatacept in treating GCA and TAK and preventing disease relapse.

Participation in this study may last up to 4 years. Participants will receive abatacept intravenously on specified days during Months 1, 2, and 3. They will also receive daily prednisone, which will be started at a dose of 40 to 60mg, then tapered to 20mg by Month 3, and finally further tapered until discontinuation is reached. At Month 3, participants who have achieved remission will be randomly assigned under double-blind conditions to either continue abatacept or be switched to placebo infusions. Both treatments will be given once a month at study visits. Blood samples will also be collected at the monthly study visits to conduct laboratory-based studies. Participants who remain in remission will continue to receive abatacept or placebo monthly until the common closing date, defined as 12 months after enrollment of the 33rd participant for each disease.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00556439

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Maryland
Johns Hopkins Medical Center
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Boston University
Boston, Massachusetts, United States, 02118
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15261
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Canada, Ontario
St. Joseph's Hospital
Hamilton, Ontario, Canada, L8P 3B3
Mt. Sinai Hospital Toronto
Toronto, Ontario, Canada, M5T 3L9
Sponsors and Collaborators
The Cleveland Clinic
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Carol A. Langford, MD, MHS The Cleveland Clinic
  More Information

Additional Information:
No publications provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier: NCT00556439     History of Changes
Obsolete Identifiers: NCT00788268
Other Study ID Numbers: N01 AR070018, 268200700036C-5-0-1, HHSN2682007000036C
Study First Received: November 9, 2007
Last Updated: April 8, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS):
Vasculitis
Arteritis
Takayasu's
Temporal Arteritis
Abatacept

Additional relevant MeSH terms:
Arteritis
Takayasu Arteritis
Aortic Arch Syndromes
Giant Cell Arteritis
Polymyalgia Rheumatica
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Aortic Diseases
Skin Diseases, Vascular
Skin Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014