Brief Title
Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis
Official Title
A Multi-Center, Open-label Pilot Study of Abatacept (CTLA4-Ig) in the Treatment of Mild Relapsing Wegener's Granulomatosis
Brief Summary
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.
Detailed Description
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Safety of Abatacept - Number of Participants With Adverse Events
Secondary Outcome
Disease Remission
Condition
Wegener's Granulomatosis
Intervention
Abatacept
Study Arms / Comparison Groups
1
Description: Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
February 2008
Completion Date
August 2011
Primary Completion Date
August 2011
Eligibility Criteria
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
Gender
All
Ages
15 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Carol A. Langford, MD, MHS, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00468208
Organization ID
RDCRN 5522
Secondary IDs
U54AR057319
Responsible Party
Sponsor
Study Sponsor
University of Pennsylvania
Collaborators
Office of Rare Diseases (ORD)
Study Sponsor
Carol A. Langford, MD, MHS, Principal Investigator, The Cleveland Clinic
Verification Date
December 2015