Wegener's GranulomatosisPhase 1/2NCT00468208
Abatacept in Treating Adults With Mild Relapsing Wegener's Granulomatosis
A Phase 1/2 study testing Abatacept in people with Wegener's Granulomatosis, run by University of Pennsylvania at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Wegener's Granulomatosis
- What is being tested?
- Abatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2008to Aug 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 16Show fewer
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The Johns Hopkins Vasculitis Center
Baltimore, Maryland, 21224
Boston University School of Medicine
Boston, Massachusetts, 02118
Cleveland Clinic
Cleveland, Ohio, 44195
Mayo Clinic College of Medicine
Rochester, Minnesota, 55905
About this study
Official title: A Multi-Center, Open-label Pilot Study of Abatacept (CTLA4-Ig) in the Treatment of 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.
Read the 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.
- Conditions
- Wegener's Granulomatosis
- Being tested
- Abatacept
- Keywords
- Vasculitis, Relapse, Wegener's, Treatment
- Medical subject headings
- Granulomatosis with Polyangiitis, Vasculitis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter. Receives: Drug: Abatacept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Measured continuously from the screening visit through to the 6 month post-treatment study visit, up to 3 years and 4 months.
Secondary outcomes (4)
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.
Measured: Measured monthly until common closing or early termination,up to 3 years and 4 months.
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.
Measured: Measured monthly until common closing or early termination, up to 3 years and 4 months.
Meeting Common Closing
The number of subjects that reached the common closing date.
Measured: Number assessed at the time of common closing, up to 3 years and 4 months.
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.
Measured: Measured monthly until common closing or early termination, up to 3 years and 4 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2007 (estimated)
- Study startFeb 2008
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Wegener's GranulomatosisStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Office of Rare Diseases (ORD), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Rare Diseases Clinical Research Network
- Responsible party
- Sponsor
- Investigators
- Carol A. Langford, MD, MHS, Principal investigator, The Cleveland ClinicPeter A. Merkel, MD, MPH, Principal investigator, Boston University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00468208
- Sponsor's protocol ID
- RDCRN 5522
- Other IDs
- U54AR057319
- Status last verified
- Dec 2015
- First submitted
- 30 Apr 2007
- Last updated
- 18 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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. doi: 10.1056/NEJMoa050524.
PubMed 16162882Langford 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.
PubMed 12727579Wegener'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.
PubMed 15673801Langford 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.
PubMed 24323392
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-label Pilot Study of Abatacept (CTLA4-Ig) in the Treatment of Mild Relapsing Wegener's Granulomatosis
- ClinicalTrials.gov ID
- NCT00468208
- Acronym / sponsor ID
- RDCRN 5522
- Conditions
- Wegener's Granulomatosis
- Keywords
- Vasculitis, Relapse, Wegener's, Treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Office of Rare Diseases (ORD), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Rare Diseases Clinical Research Network
- Study start
- Feb 2008
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 2 May 2007 (estimated)
- Results
- Posted 26 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AbataceptParticipants will receive abatacept intravenously at study visits on Days 1, 15, and 29, and then once a month thereafter. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- 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):
- 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
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbataceptA 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. | Drug | 1 |
Primary outcome
Safety of Abatacept - Number of Participants With Adverse Events
Time frame: Measured continuously from the screening visit through to the 6 month post-treatment study visit, up to 3 years and 4 months.
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.
4 secondary outcomes
Disease Remission
Time frame: Measured monthly until common closing or early termination,up to 3 years and 4 months.
Disease Improvement
Time frame: Measured monthly until common closing or early termination, up to 3 years and 4 months.
Meeting Common Closing
Time frame: Number assessed at the time of common closing, up to 3 years and 4 months.
Disease Relapse
Time frame: Measured monthly until common closing or early termination, up to 3 years and 4 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16162882Genovese 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.
- Background: PubMed 12727579Langford 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.
- Background: PubMed 15673801Wegener'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 publication: PubMed 24323392Langford 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.
- Cleveland Clinic Center for Vasculitis Care and Research websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carol A. Langford, MD, MHS principal investigator
The Cleveland Clinic
Peter A. Merkel, MD, MPH principal investigator
Boston University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Abatacept in people with Wegener's Granulomatosis, run by University of Pennsylvania at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Abatacept - Number of Participants With Adverse Events (time frame: Measured continuously from the screening visit through to the 6 month post-treatment study visit, up to 3 years and 4 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00468208, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2016.