Abatacept in ANCA Associated Vasculitis (ABAVAS)
Primary Purpose
ANCA-associated Vasculitis
Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Abatacept (Orencia)
Sponsored by
About this trial
This is an interventional prevention trial for ANCA-associated Vasculitis focused on measuring Wegener's granulomatosis, Microscopic polyangiitis, Churg Strauss Syndrome, ANCA
Eligibility Criteria
Inclusion Criteria:
- Acute AAV, presenting at first diagnosis or relapse, defined by clinical presentation
- ANCA positivity (anti-MPO or anti-PR3 positive)
- BVAS score of > 8.
Exclusion Criteria:
- Severe life-threatening disease, i.e. lung haemorrhage at the time of presentation, renal impairment with SCr>150 micromol/l, or severe CNS dysfunction thought to be due to vasculitis.
- Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological or cerebral disease, or other medical conditions that might place the subject at unacceptable risk for participation in this study.
- Any other non-vasculitic multisystem autoimmune disease
- Serious acute or bacterial infection unless treated and completely resolved with antibiotics prior to enrolment
- With any severe chronic or recurrent bacterial infection
- With Hepatitis B or C or HIV
- With Herpes zoster infection that resolved less than 2 months prior to enrolment
- Subjects who have received any live vaccines within 3 months of the first dose of study medication or who will have need of a live vaccine at any time in the year following enrolment
- Subjects with current clinical or laboratory evidence of active or latent tuberculosis (TB) and subjects with a history of active TB treated within the last 3 years
- With any previous malignancy, with the exception of non-melanoma skin malignancies, adequately treated previously
- Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional evaluations. Mammograms (females only) must be performed within 6 months of study entry or if documentation is not on file.
- With MTX treatment in prior 3 months
- Subjects with prior therapy with rituximab, anti-TNF therapy, or IL-1 receptor antagonists within last year or cyclophosphamide within last six months
- Subjects with a history of intolerance to methotrexate
- Subjects who have at any time received treatment with abatacept
- Subjects who have received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose
- Subject receiving approved or investigational biologics
Subjects with any of the following laboratory values:
- Hgb < 8.5 g/dL.
- WBC < 3,000/mm3 (3 x 109/L)
- Platelets < 100,000/mm3 (100 x 109/L).
- Serum ALT or AST > 2 times upper limit of normal.
- Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
- Subjects participating concurrently in another clinical trial
- Pregnancy, breast feeding or inadequate contraception if female.
- Allergy to a study medication
Sites / Locations
- Imperial College London, Hammersmith Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
1
2
Arm Description
Abatacept (Orencia)
saline placebo
Outcomes
Primary Outcome Measures
Relapse rate over 24 months.
Secondary Outcome Measures
Proportion of patients in sustained remission (i.e. remission at 3 months sustained for 6 months and remission at 6 months sustained for a further 12 months);
Time to remission;
The average steroid dosage at 6 months, 1 year, 18 months and 2 years in abatacept and placebo groups respectively;
Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA.
Proportion of patients defaulting to cyclophosphamide (MMF, azathioprine or other rescue) therapy.
Proportion of patients unable to stick with trial protocol.
Degree of chronic disease activity
Health related quality of life
Full Information
NCT ID
NCT00482066
First Posted
June 1, 2007
Last Updated
May 28, 2015
Sponsor
Imperial College London
Collaborators
Bristol-Myers Squibb
1. Study Identification
Unique Protocol Identification Number
NCT00482066
Brief Title
Abatacept in ANCA Associated Vasculitis
Acronym
ABAVAS
Official Title
A Pilot Study Examining the Effect of Abatacept in ANCA Associated Vasculitis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Terminated
Why Stopped
Funders withdrew funding due to slow recruitment
Study Start Date
November 2007 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College London
Collaborators
Bristol-Myers Squibb
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to investigate whether abatacept can prevent relapse in patients with ANCA associated vasculitis(AAV). This is a randomised double blinded placebo controlled trial.
Detailed Description
The drugs that are normally used to treat patients with AAV are quite effective, but up to 20% of patients relapse within 18 months. The drugs used can also have significant side effects. Abatacept, also known as CTLA4Ig, acts by blocking vital costimulatory signals required for T lymphocytes to be activated. As ANCA associated vasculitis is believed to be an autoimmune condition and dependent on autoreactive T cells, there is some reason to believe this drug would be effective. Abatacept has already received a license by the FDA for use in Rheumatoid arthritis where it has proven to be effective even in patients unresponsive to Etanercept (TNF blockade).
120 patients with AAV will be invited to take part in this study, from hospitals in the UK and Europe. The patients will receive standard therapy with methotrexate and steroids as well as 12 months of abatacept or placebo. They will be followed for a further 12 months.
The primary objective of this study is to assess the relapse rate over 24 months, in patients with acute AAV, presenting at first diagnosis or relapse, in the two arms of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ANCA-associated Vasculitis
Keywords
Wegener's granulomatosis, Microscopic polyangiitis, Churg Strauss Syndrome, ANCA
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Abatacept (Orencia)
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
saline placebo
Intervention Type
Drug
Intervention Name(s)
Abatacept (Orencia)
Intervention Description
500mg for patients under 60kg 750mg for patients 60-100kg
1g for patients>100kg given as i.v. infusion over 30 minutes at day 0, 14, 28 and then monthly for a further 11 months 914 infusions in total) placebo groups receive saline only I.v.
Primary Outcome Measure Information:
Title
Relapse rate over 24 months.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Proportion of patients in sustained remission (i.e. remission at 3 months sustained for 6 months and remission at 6 months sustained for a further 12 months);
Time Frame
2 years
Title
Time to remission;
Time Frame
2 years
Title
The average steroid dosage at 6 months, 1 year, 18 months and 2 years in abatacept and placebo groups respectively;
Time Frame
2 years
Title
Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA.
Time Frame
2 years
Title
Proportion of patients defaulting to cyclophosphamide (MMF, azathioprine or other rescue) therapy.
Time Frame
2 years
Title
Proportion of patients unable to stick with trial protocol.
Time Frame
2 years
Title
Degree of chronic disease activity
Time Frame
2 years
Title
Health related quality of life
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Acute AAV, presenting at first diagnosis or relapse, defined by clinical presentation
ANCA positivity (anti-MPO or anti-PR3 positive)
BVAS score of > 8.
Exclusion Criteria:
Severe life-threatening disease, i.e. lung haemorrhage at the time of presentation, renal impairment with SCr>150 micromol/l, or severe CNS dysfunction thought to be due to vasculitis.
Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological or cerebral disease, or other medical conditions that might place the subject at unacceptable risk for participation in this study.
Any other non-vasculitic multisystem autoimmune disease
Serious acute or bacterial infection unless treated and completely resolved with antibiotics prior to enrolment
With any severe chronic or recurrent bacterial infection
With Hepatitis B or C or HIV
With Herpes zoster infection that resolved less than 2 months prior to enrolment
Subjects who have received any live vaccines within 3 months of the first dose of study medication or who will have need of a live vaccine at any time in the year following enrolment
Subjects with current clinical or laboratory evidence of active or latent tuberculosis (TB) and subjects with a history of active TB treated within the last 3 years
With any previous malignancy, with the exception of non-melanoma skin malignancies, adequately treated previously
Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional evaluations. Mammograms (females only) must be performed within 6 months of study entry or if documentation is not on file.
With MTX treatment in prior 3 months
Subjects with prior therapy with rituximab, anti-TNF therapy, or IL-1 receptor antagonists within last year or cyclophosphamide within last six months
Subjects with a history of intolerance to methotrexate
Subjects who have at any time received treatment with abatacept
Subjects who have received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose
Subject receiving approved or investigational biologics
Subjects with any of the following laboratory values:
Hgb < 8.5 g/dL.
WBC < 3,000/mm3 (3 x 109/L)
Platelets < 100,000/mm3 (100 x 109/L).
Serum ALT or AST > 2 times upper limit of normal.
Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
Subjects participating concurrently in another clinical trial
Pregnancy, breast feeding or inadequate contraception if female.
Allergy to a study medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan Salama
Organizational Affiliation
Imperial College London
Official's Role
Study Director
Facility Information:
Facility Name
Imperial College London, Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
12. IPD Sharing Statement
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Abatacept in ANCA Associated Vasculitis
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