ABAVAS 2008.

Methods	A phase III, multi‐centre, randomised, double‐blind, placebo‐controlled trial with two arms: 1. arm ‐ abatacept 250 mg intravenous 2. arm ‐ placebo
Participants	Inclusion criteria: Informed consent Participants (females not nursing and not pregnant) ≥18 years of age. Females of childbearing potential practicing an acceptable method of birth control. First diagnosis of acute AAV or relapse of AAV (Wegener’s Granulomatosis, microscopic polyangiitis or Churg‐Strauss syndrome and ANCA positivity (positive for anti‐MPO or anti‐PR3) or historical ANCA positivity, and a BVAS score of > 8. Exclusion criteria: Severe life‐threatening condition, i.e. lung haemorrhage, renal impairment with serum creatinine > 150 µmol/l, or severe central nervous system dysfunction regarded as associated with vasculitis. Current symptoms of any severe, progressive, or uncontrolled disease or medical conditions which may cause an unacceptable risk for participation in this trial. Any other non‐vasculitic multisystem autoimmune disease. Any serious acute bacterial infection not resolved completely with antibiotics before enrolment Any severe chronic or recurrent bacterial infection, Hepatitis B or C or HIV positive status. Herpes zoster infection resolved <2 months before enrolment. Received a live vaccine within 3 months before the first dose of study drug or a need of a live vaccine during the year following enrolment. Active or latent tuberculosis (clinical or laboratory evidence) or active tuberculosis within the last three years Any previous cancer, except properly treated non‐melanoma skin cancer Any mammogram suspicious for malignancy performed within 6 months before study Hemoglobin below < 8.5 g/dL, white blood count below 3,000/mm3 (3 x 109/L), Platelets count below 100,000/mm3 (100 x 109/L), serum aminotransferase (alanine or aspartate) above 2 times upper limit of normal or any other results of laboratory tests which might be associated with an unacceptable risk for study participation. Concurrent participant in another clinical trial. Pregnant or breast feeding. Allergy to a study medication or intolerance to methotrexate. Previous treatment: abatacept any time investigational drug within 28 days (or >5 terminal half‐lives) currently treated with biological agent methotrexate within 3 months rituximab, anti‐TNF therapy, or IL‐1 receptor antagonists within last year cyclophosphamide within last six months.
Interventions	Arm 1: Abatacept 500 mg for patients under 60kg 750mg for patients 60‐100kg 1g for patients > 100kg given as IV infusion over 30 minutes at day 0, 14, 28 and then monthly for a further 11 months 914 infusions in total) Arm 2: saline placebo only IV
Outcomes	Major outcome: Relapse rate over 24 months. Minor outcomes: The proportion of patients in sustained remission at 6, 12, 18 months and 24 months The time to remission The average steroid dosage at 6, 12,18 and 24 months The time to ANCA negativity by immunofluorescence or negative anti‐PR3 or anti‐MPO anitbody test by ELISA Urinary MCP‐1 measurement to assess disease activity Proportion of patients defaulting to cyclophosphamide (mycophenolate mofetil, azathioprine or other rescue) therapy Proportion of patients unable to stick with trial protocol. Degree of chronic disease activity Health related quality of life
Notes	Contact person: Alan Salama Imperial College London ClinicalTrials.gov Identifier: NCT00482066 EudraCT number 2006‐001859‐35