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

NCT ID: NCT00556439

Last Updated: 2018-02-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2015-08-31

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.

Conditions

Takayasu's Arteritis; Giant Cell Arteritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Abatacept

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Abatacept

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo abatacept infusions will be given monthly after random assignment at Month 3.

Interventions

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.

Intervention Type: DRUG

Placebo

Placebo abatacept infusions will be given monthly after random assignment at Month 3.

Intervention Type: DRUG

Other Intervention Names

Orencia

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

• 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

• 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

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

Office of Rare Diseases (ORD)

NIH

Sponsor Role: collaborator

Rare Diseases Clinical Research Network

NETWORK

Sponsor Role: collaborator

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

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carol A. Langford, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Johns Hopkins Medical Center

Baltimore, Maryland, United States

Boston University

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Hospital for Special Surgery

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

St. Joseph's Hospital

Hamilton, Ontario, Canada

Mt. Sinai Hospital Toronto

Toronto, Ontario, Canada

Countries

United States; Canada

References

Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear CA, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. Arthritis Rheumatol. 2017 Apr;69(4):846-853. doi: 10.1002/art.40037. Epub 2017 Mar 8.

Reference Type: DERIVED

PMID: 28133931 (View on PubMed)

Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, Seo P, Moreland LW, Weisman M, Koening CL, Sreih AG, Spiera R, McAlear CA, Warrington KJ, Pagnoux C, McKinnon K, Forbess LJ, Hoffman GS, Borchin R, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Giant Cell Arteritis. Arthritis Rheumatol. 2017 Apr;69(4):837-845. doi: 10.1002/art.40044. Epub 2017 Mar 3.

Reference Type: DERIVED

PMID: 28133925 (View on PubMed)

Goldstein BL, Gedmintas L, Todd DJ. Drug-associated polymyalgia rheumatica/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of ctla-4. Arthritis Rheumatol. 2014 Mar;66(3):768-9. doi: 10.1002/art.38282. No abstract available.

Reference Type: DERIVED

PMID: 24574239 (View on PubMed)

Related Links

http://www.clevelandclinic.org/arthritis/vasculitis

Click here for the Cleveland Clinic Center for Vasculitis Care and Research Web site

Other Identifiers

268200700036C-5-0-1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HHSN2682007000036C

Identifier Type: -

Identifier Source: secondary_id

N01 AR070018

Identifier Type: -

Identifier Source: org_study_id

NCT00788268

Identifier Type: -

Identifier Source: nct_alias