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| Sponsor: | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
|---|---|
| Collaborators: |
Office of Rare Diseases (ORD) Rare Diseases Clinical Research Network |
| Information provided by: | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) |
| ClinicalTrials.gov Identifier: | NCT00556439 |
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 II |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study |
| 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 |
| Estimated Enrollment: | 66 |
| Study Start Date: | December 2008 |
| Estimated Study Completion Date: | February 2012 |
| Estimated Primary Completion Date: | February 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
A: Experimental
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:
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. |
|
B: Placebo Comparator
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:
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.
Placebo abatacept infusions will be given monthly after random assignment at Month 3.
|
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: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Specific Inclusion Criteria for Participants with GCA:
Participants must meet three of the following five criteria, including either Criterion 4 or 5:
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:
Exclusion Criteria:
Presence of any of the following diseases or conditions:
Contacts and Locations| Contact: Carol A. Langford, MD, MHS | 216-445-6056 | langfoc@ccf.org |
| United States, Maryland | |
| Johns Hopkins Medical Center | Recruiting |
| Baltimore, Maryland, United States, 21224 | |
| Contact: Philip Seo, MD 410-550-6825 | |
| Principal Investigator: Philip Seo, MD | |
| United States, Massachusetts | |
| Boston University | Recruiting |
| Boston, Massachusetts, United States, 02118 | |
| Contact: Peter A. Merkel, MD, MPH 617-414-2500 | |
| Principal Investigator: Peter A. Merkel, MD, MPH | |
| United States, Minnesota | |
| Mayo Clinic | Not yet recruiting |
| Rochester, Minnesota, United States, 55905 | |
| Contact: Eric Matteson, MD 507-284-8450 | |
| Principal Investigator: Eric Matteson, MD | |
| United States, Ohio | |
| Cleveland Clinic | Recruiting |
| Cleveland, Ohio, United States, 44195 | |
| Contact: Carol A. Langford, MD MHS 216-445-6056 | |
| Principal Investigator: Carol A. Langford, MD MHS | |
| Principal Investigator: | Carol A. Langford, MD, MHS | Cleveland Clinic |
More Information
| Responsible Party: | Cleveland Clinic ( Carol Langford ) |
| Study ID Numbers: | N01 AR070018, HHSN2682007000018C |
| Study First Received: | November 9, 2007 |
| Last Updated: | April 24, 2009 |
| ClinicalTrials.gov Identifier: | NCT00556439 History of Changes |
| Health Authority: | United States: Federal Government |
|
Vasculitis Arteritis Takayasu's Temporal Arteritis Abatacept |
|
Immunologic Factors Physiological Effects of Drugs Vasculitis, Central Nervous System Brain Diseases Cerebrovascular Disorders Abatacept Musculoskeletal Diseases Therapeutic Uses Connective Tissue Diseases Cardiovascular Diseases Arteritis Autoimmune Diseases of the Nervous System Skin Diseases, Vascular Vasculitis Autoimmune Diseases |
Skin Diseases Immune System Diseases Takayasu Arteritis Nervous System Diseases Vascular Diseases Central Nervous System Diseases Rheumatic Diseases Immunosuppressive Agents Pharmacologic Actions Aortic Diseases Muscular Diseases Polymyalgia Rheumatica Giant Cell Arteritis Aortic Arch Syndromes Antirheumatic Agents |