Abatacept in ANCA Associated Vasculitis
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.
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