Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis - Full Text View

Sponsor:	Boston University
Collaborators:	Office of Rare Diseases (ORD) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Rare Diseases Clinical Research Network
Information provided by (Responsible Party):	Peter A. Merkel, Boston University
ClinicalTrials.gov Identifier:	NCT00468208

Purpose

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.

Condition	Intervention	Phase
Wegener's Granulomatosis	Drug: Abatacept	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Multi-Center, Open-label Pilot Study of Abatacept (CTLA4-Ig) in the Treatment of Mild Relapsing Wegener's Granulomatosis

Resource links provided by NLM:

MedlinePlus related topics: Vasculitis Wegener's Granulomatosis

Drug Information available for: Abatacept

U.S. FDA Resources

Further study details as provided by Boston University:

Primary Outcome Measures:

Safety of abatacept [ Time Frame: Measured monthly during study and 1, 3, and 6 months post-treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Efficacy of abatacept [ Time Frame: Measured monthly during study and 1, 3, and 6 months post-treatment ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	February 2008
Estimated Study Completion Date:	June 2013
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter for a total of 6 to 18 months.	Drug: Abatacept A participant's abatacept dose will depend on body weight and will remain the same throughout the study: 500 mg of abatacept for body weight less than 60 kg 750 mg of abatacept for body weight between 60 and 100 kg 1000 mg of abatacept for body weight greater than 100 kg Abatacept will be administered in a 30-minute intravenous infusion.

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.

Participation in this study may last between 7 and 24 months. 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 will depend 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 receiving 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 be back to the same dose that they had been on prior to relapse by Month 2. All study visits will 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 may occur at some study visits. Participants whose symptoms have not improved by Month 2 will stop receiving abatacept. All participants will attend three follow-up study visits that will occur 1, 3, and 6 months after the end of treatment.

Eligibility

Ages Eligible for Study:	15 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00468208

Locations

United States, Maryland
The Johns Hopkins Vasculitis Center
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Boston University School of Medicine
Boston, Massachusetts, United States, 02118
United States, Minnesota
Mayo Clinic College of Medicine
Rochester, Minnesota, United States, 55905
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Boston University

Office of Rare Diseases (ORD)

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

Rare Diseases Clinical Research Network

Investigators

Principal Investigator:	Carol A. Langford, MD, MHS	The Cleveland Clinic
Principal Investigator:	Peter A. Merkel, MD, MPH	Boston University

More Information

Additional Information:

Vasculitis Clinical Research Consortium website This link exits the ClinicalTrials.gov site

Cleveland Clinic Center for Vasculitis Care and Research website This link exits the ClinicalTrials.gov site

Publications:

Genovese MC, Becker JC, Schiff M, Luggen M, Sherrer Y, Kremer J, Birbara C, Box J, Natarajan K, Nuamah I, Li T, Aranda R, Hagerty DT, Dougados M. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med. 2005 Sep 15;353(11):1114-23. Erratum in: N Engl J Med. 2005 Nov 24;353(21):2311.

Langford CA, Talar-Williams C, Barron KS, Sneller MC. Use of a cyclophosphamide-induction methotrexate-maintenance regimen for the treatment of Wegener's granulomatosis: extended follow-up and rate of relapse. Am J Med. 2003 Apr 15;114(6):463-9.

Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. 2005 Jan 27;352(4):351-61.

Responsible Party:	Peter A. Merkel, Professor, Boston University
ClinicalTrials.gov Identifier:	NCT00468208 History of Changes
Other Study ID Numbers:	RDCRN 5522, U54AR057319
Study First Received:	April 30, 2007
Last Updated:	February 2, 2012
Health Authority:	United States: Federal Government

Keywords provided by Boston University:

Vasculitis
Relapse
Wegener's
Treatment

Additional relevant MeSH terms:

Wegener Granulomatosis
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Systemic Vasculitis
Vasculitis
Vascular Diseases

Cardiovascular Diseases
Abatacept
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 22, 2012