Abatacept in ANCA Associated Vasculitis (ABAVAS)

Imperial College London

Status and phase

Terminated

Phase 2

Conditions

ANCA-associated Vasculitis

Treatments

Drug: Abatacept (Orencia)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00482066

2006-001859-35 (EudraCT Number)

BMS protocol No: IST110 (Other Grant/Funding Number)

cro632

Details and patient eligibility

About

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.

Full 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.

Enrollment

7 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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