Abatacept in ANCA Associated Vasculitis (ABAVAS)

May 28, 2015 updated by: Imperial College London

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.

Study Overview

Status

Terminated

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • London, United Kingdom, W12 0NN
        • Imperial College London, Hammersmith Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
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

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Relapse rate over 24 months.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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 years
Time to remission;
Time Frame: 2 years
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
2 years
Time to ANCA negativity by immunofluorescence or negative anti-PR3 or anti-MPO Ab test by ELISA.
Time Frame: 2 years
2 years
Proportion of patients defaulting to cyclophosphamide (MMF, azathioprine or other rescue) therapy.
Time Frame: 2 years
2 years
Proportion of patients unable to stick with trial protocol.
Time Frame: 2 years
2 years
Degree of chronic disease activity
Time Frame: 2 years
2 years
Health related quality of life
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Director: Alan Salama, Imperial College London

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

June 1, 2007

First Submitted That Met QC Criteria

June 1, 2007

First Posted (Estimate)

June 4, 2007

Study Record Updates

Last Update Posted (Estimate)

May 29, 2015

Last Update Submitted That Met QC Criteria

May 28, 2015

Last Verified

March 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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