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

January 25, 2018 updated by: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

97

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8P 3B3
        • St. Joseph's Hospital
      • Toronto, Ontario, Canada, M5T 3L9
        • Mt. Sinai Hospital Toronto
  • United States
    • California
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10021
        • Hospital for Special Surgery
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15261
        • University of Pittsburgh
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A and C
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 for giant cell arteritis and Group C for Takayasu arteritis.
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 (giant cell arteritis) and Group C (Takayasu arteritis) participants will continue on abatacept.

Other Names:
  • Orencia
Placebo Comparator: B and D
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 for giant cell arteritis and Group D for Takayasu arteritis.
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 (giant cell arteritis) and Group C (Takayasu arteritis) participants will continue on abatacept.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Outcome - Relapse-free Survival (RFS)
Time Frame: Weeks 0 to 64

Relapse: presence of active disease occurring after a period of remission

Remission: absence of active disease

Active disease defined by clinical features or imaging or both:

Clinical features:

1 or more of the following attributed to GCA/TAK:

  • Sustained fever of >38 C for > 1 week
  • Vascular pain/tenderness > 1 day, non-fleeting
  • Headache a) present > 1 day b) non-fleeting c) not relieved with analgesics d) not typical for pre-existing headaches
  • Ischemic retinopathy, optic neuropathy, or visual loss
  • Tongue/jaw pain and/or claudication
  • TIA or stroke
  • Extremity claudication
  • Musculoskeletal symptoms + ESR of > 40 mm/hr or CRP above the normal limit
  • Malaise/fatigue + ESR of > 40 mm/hr or CRP above the normal limit
  • Other symptoms/signs due to GCA/TAK requiring reinstitution/increase in GC

Imaging features

• Development of new vascular stenosis or aneurysm in new vascular territories as seen by MRI/MRA or arteriogram
Weeks 0 to 64

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborators

The Cleveland Clinic
Rare Diseases Clinical Research Network
Office of Rare Diseases (ORD)

Investigators

  • Principal Investigator: Carol A. Langford, MD, MHS, The Cleveland Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

November 9, 2007

First Submitted That Met QC Criteria

November 9, 2007

First Posted (Estimate)

November 12, 2007

Study Record Updates

Last Update Posted (Actual)

February 26, 2018

Last Update Submitted That Met QC Criteria

January 25, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N01 AR070018
  • 268200700036C-5-0-1 (U.S. NIH Grant/Contract)
  • HHSN2682007000036C

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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