Abatacept in ANCA Associated Vasculitis (ABAVAS)

This study has been terminated.
(Funders withdrew funding due to slow recruitment)
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
Imperial College London
ClinicalTrials.gov Identifier:
NCT00482066
First received: June 1, 2007
Last updated: May 25, 2010
Last verified: May 2010

June 1, 2007
May 25, 2010
November 2007
December 2010   (final data collection date for primary outcome measure)
Relapse rate over 24 months. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Relapse rate over 24 months. [ Time Frame: 2 years ]
Complete list of historical versions of study NCT00482066 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • Time to remission; [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • The average steroid dosage at 6 months, 1 year, 18 months and 2 years in abatacept and placebo groups respectively; [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Proportion of patients defaulting to cyclophosphamide (MMF, azathioprine or other rescue) therapy. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Proportion of patients unable to stick with trial protocol. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Degree of chronic disease activity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Health related quality of life [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • 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 ]
  • Time to remission; [ Time Frame: 2 years ]
  • The average steroid dosage at 6 months, 1 year, 18 months and 2 years in abatacept and placebo groups respectively; [ Time Frame: 2 years ]
  • Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA. [ Time Frame: 2 years ]
  • Proportion of patients defaulting to cyclophosphamide (MMF, azathioprine or other rescue) therapy. [ Time Frame: 2 years ]
  • Proportion of patients unable to stick with trial protocol. [ Time Frame: 2 years ]
  • Degree of chronic disease activity [ Time Frame: 2 years ]
  • Health related quality of life [ Time Frame: 2 years ]
Not Provided
Not Provided
 
Abatacept in ANCA Associated Vasculitis
A Pilot Study Examining the Effect of Abatacept in ANCA Associated Vasculitis

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
ANCA-associated Vasculitis
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.

  • Experimental: 1
    abatacept
    Intervention: Drug: Abatacept (Orencia)
  • Placebo Comparator: 2
    saline placebo
    Intervention: Drug: Abatacept (Orencia)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
7
December 2010
December 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT00482066
cro632, Eudract No: 2006-001859-35, BMS protocol No: IST110
Yes
Alan Salama, Imperial College London
Imperial College London
Bristol-Myers Squibb
Study Director: Alan Salama Imperial College London
Imperial College London
May 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP