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Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis

Primary Purpose

Wegener's Granulomatosis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Abatacept
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wegener's Granulomatosis focused on measuring Vasculitis, Relapse, Wegener's, Treatment

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The Johns Hopkins Vasculitis Center
  • Boston University School of Medicine
  • Mayo Clinic College of Medicine
  • Cleveland Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

1

Arm Description

Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter.

Outcomes

Primary Outcome Measures

Safety of Abatacept - Number of Participants With Adverse Events
This study examined the safety profile of this agent when used in Wegener's granulomatosis. Information was gathered on all adverse events with specific events being identified in the protocol for analysis that included the following: Infection Infusion reactions Cytopenias Transaminase elevation Skin reactions GI side effects Malignancy All adverse events were reportable for this study.

Secondary Outcome Measures

Disease Remission
Disease remission was measured by a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0. The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63.
Disease Improvement
Disease improvement was measured by a reduction in the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63.
Meeting Common Closing
The number of subjects that reached the common closing date.
Disease Relapse
Disease relapse was measured by a rise in the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of greater than or equal to 1 after achieving remission. The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63.

Full Information

First Posted
April 30, 2007
Last Updated
December 15, 2015
Sponsor
University of Pennsylvania
Collaborators
Office of Rare Diseases (ORD), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Rare Diseases Clinical Research Network
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1. Study Identification

Unique Protocol Identification Number
NCT00468208
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
February 2008 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
Office of Rare Diseases (ORD), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Rare Diseases Clinical Research Network

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wegener's Granulomatosis
Keywords
Vasculitis, Relapse, Wegener's, Treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter.
Intervention Type
Drug
Intervention Name(s)
Abatacept
Intervention Description
A participant's abatacept dose depended 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 is administered in a 30-minute intravenous infusion.
Primary Outcome Measure Information:
Title
Safety of Abatacept - Number of Participants With Adverse Events
Description
This study examined the safety profile of this agent when used in Wegener's granulomatosis. Information was gathered on all adverse events with specific events being identified in the protocol for analysis that included the following: Infection Infusion reactions Cytopenias Transaminase elevation Skin reactions GI side effects Malignancy All adverse events were reportable for this study.
Time Frame
Measured continuously from the screening visit through to the 6 month post-treatment study visit, up to 3 years and 4 months.
Secondary Outcome Measure Information:
Title
Disease Remission
Description
Disease remission was measured by a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0. The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63.
Time Frame
Measured monthly until common closing or early termination,up to 3 years and 4 months.
Title
Disease Improvement
Description
Disease improvement was measured by a reduction in the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63.
Time Frame
Measured monthly until common closing or early termination, up to 3 years and 4 months.
Title
Meeting Common Closing
Description
The number of subjects that reached the common closing date.
Time Frame
Number assessed at the time of common closing, up to 3 years and 4 months.
Title
Disease Relapse
Description
Disease relapse was measured by a rise in the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of greater than or equal to 1 after achieving remission. The BVAS/WG is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63.
Time Frame
Measured monthly until common closing or early termination, up to 3 years and 4 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
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): Sinonasal disease Oral mucosa ulceration Skin disease Musculoskeletal disease Pulmonary parenchymal disease Mild ocular disease Subglottic inflammation without significant stenosis Otic disease Breast involvement Urogenital involvement 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carol A. Langford, MD, MHS
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter A. Merkel, MD, MPH
Organizational Affiliation
Boston University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Johns Hopkins Vasculitis Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Boston University School of Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Mayo Clinic College of Medicine
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16162882
Citation
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. doi: 10.1056/NEJMoa050524. Erratum In: N Engl J Med. 2005 Nov 24;353(21):2311.
Results Reference
background
PubMed Identifier
12727579
Citation
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. doi: 10.1016/s0002-9343(03)00077-9.
Results Reference
background
PubMed Identifier
15673801
Citation
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. doi: 10.1056/NEJMoa041884.
Results Reference
background
PubMed Identifier
24323392
Citation
Langford CA, Monach PA, Specks U, Seo P, Cuthbertson D, McAlear CA, Ytterberg SR, Hoffman GS, Krischer JP, Merkel PA; Vasculitis Clinical Research Consortium. An open-label trial of abatacept (CTLA4-IG) in non-severe relapsing granulomatosis with polyangiitis (Wegener's). Ann Rheum Dis. 2014 Jul;73(7):1376-9. doi: 10.1136/annrheumdis-2013-204164. Epub 2013 Dec 9.
Results Reference
result
Links:
URL
http://my.clevelandclinic.org/rheumatology_immunology/vasculitis_center
Description
Cleveland Clinic Center for Vasculitis Care and Research website

Learn more about this trial

Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis

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