The purpose of this study is to evaluate efficacy, safety and tolerability of blisibimod when taken with methotrexate in the induction of remission in ANCA-Associated Small Vessel Vasculitis.

Inclusion Criteria:

1. 18 years of age or older (male or female).
2. Granulomatosis with polyangiitis (GPA, or Wegener's granulomatosis) or microscopic polyangiitis (MPA) according to the definitions of the American College of Rheumatology and Chapel Hill Consensus Conference.
3. Active GPA or MPA disease at screening.
4. Positive for either PR3-ANCA or MPO-ANCA at screening.
5. Subject willing to initiate corticosteroids and methotrexate (MTX) if not already on corticosteroids and/or MTX at baseline.
6. Clinical intention to prescribe MTX therapy for treatment of GPA or MPA.

Exclusion Criteria:

1. Diagnosed with Churg Strauss syndrome.
2. Severe GPA or MPA disease that would conventionally be treated with cyclophosphamide.
3. Nursing or pregnant.
4. Active systemic infection or deep-space infection.
5. Active hepatitis B, active hepatitis C or a documented history of HIV, hepatitis B, or hepatitis C.
6. Liver disease.
7. History of documented anti-glomerular basement membrane (GBM) disease.
8. Malignancy within the past 5 years.
9. History of active tuberculosis (TB) or history of TB infection.
10. Anemia, neutropenia, or thrombocytopenia.
11. Serum creatinine level greater than 2.5 mg/dL.
12. Prior administration of a B-cell modulating therapy other than rituximab.
13. Subject has not yet completed at least 3 months or 5 half-lives (whichever is longer) since ending other investigational study.
14. History of congenital immunodeficiency.