Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis
Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis
Wegener's granulomatosis (WG) is a rare disease that causes inflammation of blood vessels, or
 vasculitis. It may involve many different parts of the body, but typically affects the upper
 and lower respiratory tract and kidneys. The purpose of this study is to determine the safety
 and effectiveness of the medication abatacept in treating adults with mild relapsing WG.
Current standard treatment for WG involves various medications and is based on disease
 severity. Unfortunately, more than 50% of people experience a relapse after remission,
 placing them at risk for additional organ damage and medication toxicity. To prevent this,
 safer and more effective treatments for mild relapses are needed. Several studies have shown
 that activated T cells, a type of white blood cell important in regulating immune responses,
 play a role in WG. Abatacept, an immunoglobulin-based medication approved by the FDA to treat
 rheumatoid arthritis, acts by preventing T-cell activation and may be useful in treating mild
 relapses of WG. The purpose of this study is to determine the safety and effectiveness of
 abatacept in treating adults with mild relapsing WG.

 Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and
 then once a month thereafter. A participant's abatacept dose is based on body weight and will
 remain the same throughout the study. Participants who are receiving maintenance
 immunosuppressive medications consisting of methotrexate, azathioprine, or mycophenolate
 mofetil at the time of enrollment will remain on these medications without dosage increase or
 reduction. Eligible participants may be on up to prednisone 15mg daily at the time of
 relapse. Following the development of relapse, participants may be treated with up to
 prednisone 30mg daily if necessary, but must to be back to the same dose that they had been
 on prior to relapse by Month 2. All study visits include medication review, physical exam,
 blood and urine collection, and questionnaires. A chest x-ray, computed tomography (CT) scan
 of the chest and sinuses, and lung function testing will occur at some study visits.
 Participants whose symptoms did not improved by Month 2 will be taken off abatacept. Any
 participants undergoing early termination or, after common closing, will undergo three
 follow-up study visits at 1, 3, and 6 months after the end of treatment.
Inclusion Criteria:

 -  Diagnosis of WG, meeting at least 2 of the 5 modified American College of Rheumatology
 (ACR) criteria. More information about this criterion can be found in the protocol.

 -  Relapse of WG within the past 28 days where disease activity is confined to one or
 more of the following sites and where the symptoms/signs are of such a nature that the
 usual treatment would consist of the reinstitution or increase in GC to no more than
 prednisone 30mg daily and/or an increase or addition of a second immunosuppressive
 agent other than CYC (more specific information about this criterion can be found in
 the protocol):

 1. Sinonasal disease

 2. Oral mucosa ulceration

 3. Skin disease

 4. Musculoskeletal disease

 5. Pulmonary parenchymal disease

 6. Mild ocular disease

 7. Subglottic inflammation without significant stenosis

 8. Otic disease

 9. Breast involvement

 10. Urogenital involvement

 11. Other mild disease

 -  Age of 15 years or older

 -  Willing and able to undergo treatment and attend follow-up visits

 -  Willing to use effective forms of contraception throughout the study

 Exclusion Criteria:

 -  Disease involvement that does not meet the criteria for mild disease. More information
 about this criterion can be found in the protocol.

 -  Disease activity that would usually be treated first with cyclophosphamide

 -  Presence of disease activity for which the investigator would normally treat the
 participant with more than prednisone 30 mg daily.

 -  Receiving cyclophosphamide at study entry

 -  Treatment with prednisone at a dose of more than 15 mg daily at the time of relapse.
 Subjects will be eligible if prednisone was initiated or dose increased in the period
 between relapse and study enrollment provided that the prednisone dose was 15 mg daily
 or less at the time when the relapse occurred, the prednisone dosage was increased no
 higher than 30 mg daily following the recognition of relapse, and that the dosage
 increase was made no more than 28 days prior to enrollment.

 -  Active infection

 -  HIV infected, hepatitis C virus infected, or positive for hepatitis B

 -  Unable to follow through with study participation

 -  Cytopenia, defined as platelet count less than 80,000/mm3, absolute neutrophil count
 less than 1500/mm3, OR hematocrit less than 20%

 -  Kidney insufficiency

 -  Use of illegal drugs

 -  Any other uncontrolled disease that would prevent participation

 -  History of cancer. More information about this criterion can be found in the protocol.

 -  Received an investigational medication or procedure within 30 days of study entry

 -  Received a live vaccine within 4 weeks of study entry

 -  Positive tuberculin skin test. More information about this criterion can be found in
 the protocol.

 -  Tuberculosis as indicated by radiographic evidence

 -  Past treatment with rituximab within the past 12 months, or past treatment with
 rituximab more than 12 months ago where the B lymphocyte count has not returned to
 normal

 -  Certain other diseases. More information about this criterion can be found in the
 protocol.

 -  Pregnant or breastfeeding