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
  Purpose

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 Intervention Phase
ANCA-associated Vasculitis
Drug: Abatacept (Orencia)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Pilot Study Examining the Effect of Abatacept in ANCA Associated Vasculitis

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Relapse rate over 24 months. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

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 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 ]

Enrollment: 7
Study Start Date: November 2007
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
abatacept
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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00482066

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

No publications provided

Responsible Party: Alan Salama, Imperial College London
ClinicalTrials.gov Identifier: NCT00482066     History of Changes
Other Study ID Numbers: cro632, Eudract No: 2006-001859-35, BMS protocol No: IST110
Study First Received: June 1, 2007
Last Updated: May 25, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Imperial College London:
Wegener's granulomatosis
Microscopic polyangiitis
Churg Strauss Syndrome
ANCA

Additional relevant MeSH terms:
Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Systemic Vasculitis
Autoimmune Diseases
Immune System Diseases
Abatacept
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 31, 2014