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Trial record 89 of 137 for:    "Connective Tissue Disease" | "Abatacept"

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

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ClinicalTrials.gov Identifier: NCT00556439
Recruitment Status : Completed
First Posted : November 12, 2007
Results First Posted : February 26, 2018
Last Update Posted : February 26, 2018
Sponsor:
Collaborators:
The Cleveland Clinic
Office of Rare Diseases (ORD)
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Tracking Information
First Submitted Date  ICMJE November 9, 2007
First Posted Date  ICMJE November 12, 2007
Results First Submitted Date  ICMJE April 25, 2017
Results First Posted Date  ICMJE February 26, 2018
Last Update Posted Date February 26, 2018
Study Start Date  ICMJE December 2008
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2018)
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
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2007)
Remission duration [ Time Frame: Months 0 to 48 ]
Change History Complete list of historical versions of study NCT00556439 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2007)
Drug toxicity [ Time Frame: Months 0 to 48 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu's Arteritis
Official Title  ICMJE 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
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Takayasu's Arteritis
  • Giant Cell Arteritis
Intervention  ICMJE
  • 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 Name: Orencia
  • Drug: Placebo
    Placebo abatacept infusions will be given monthly after random assignment at Month 3.
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Abatacept
  • 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.
    Interventions:
    • Drug: Abatacept
    • Drug: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 25, 2018)
97
Original Estimated Enrollment  ICMJE
 (submitted: November 9, 2007)
66
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 15 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00556439
Other Study ID Numbers  ICMJE N01 AR070018
268200700036C-5-0-1 ( U.S. NIH Grant/Contract )
HHSN2682007000036C
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Study Sponsor  ICMJE National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Collaborators  ICMJE
  • The Cleveland Clinic
  • Office of Rare Diseases (ORD)
  • Rare Diseases Clinical Research Network
Investigators  ICMJE
Principal Investigator: Carol A. Langford, MD, MHS The Cleveland Clinic
PRS Account National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP