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Abatacept in ANCA Associated Vasculitis (ABAVAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00482066
Recruitment Status : Terminated (Funders withdrew funding due to slow recruitment)
First Posted : June 4, 2007
Last Update Posted : May 29, 2015
Bristol-Myers Squibb
Information provided by (Responsible Party):
Imperial College London

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.

Condition or disease Intervention/treatment Phase
ANCA-associated Vasculitis Drug: Abatacept (Orencia) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Official Title: A Pilot Study Examining the Effect of Abatacept in ANCA Associated Vasculitis
Study Start Date : November 2007
Actual Primary Completion Date : November 2008
Actual Study Completion Date : November 2008

Arm Intervention/treatment
Active Comparator: 1
Abatacept (Orencia)
Drug: Abatacept (Orencia)

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.

Placebo Comparator: 2
saline placebo
Drug: Abatacept (Orencia)

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 Measures :
  1. Relapse rate over 24 months. [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. Time to remission; [ Time Frame: 2 years ]
  3. The average steroid dosage at 6 months, 1 year, 18 months and 2 years in abatacept and placebo groups respectively; [ Time Frame: 2 years ]
  4. Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA. [ Time Frame: 2 years ]
  5. Proportion of patients defaulting to cyclophosphamide (MMF, azathioprine or other rescue) therapy. [ Time Frame: 2 years ]
  6. Proportion of patients unable to stick with trial protocol. [ Time Frame: 2 years ]
  7. Degree of chronic disease activity [ Time Frame: 2 years ]
  8. Health related quality of life [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00482066

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United Kingdom
Imperial College London, Hammersmith Hospital
London, United Kingdom, W12 0NN
Sponsors and Collaborators
Imperial College London
Bristol-Myers Squibb
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Study Director: Alan Salama Imperial College London

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Responsible Party: Imperial College London Identifier: NCT00482066    
Other Study ID Numbers: cro632
2006-001859-35 ( EudraCT Number )
BMS protocol No: IST110 ( Other Grant/Funding Number: Bristol Myers Squib funder )
First Posted: June 4, 2007    Key Record Dates
Last Update Posted: May 29, 2015
Last Verified: March 2015
Keywords provided by Imperial College London:
Wegener's granulomatosis
Microscopic polyangiitis
Churg Strauss Syndrome
Additional relevant MeSH terms:
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Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Systemic Vasculitis
Autoimmune Diseases
Immune System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents