Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Multi-Center, Multinational, Randomized, Double-Blind, Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) in Combination With Azathioprine for the Maintenance of Remission in Wegener's Granulomatosis and Microscopic Polyangiitis
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of belimumab, in combination with azathioprine, for the maintenance of remission following a standard induction regimen in patients with Wegener's granulomatosis or microscopic polyangiitis. The random assignment in this study is "1 to 1" which means that participants have an equal chance of receiving belimumab or placebo.


Options:
A: Inclusion Criteria:

* Diagnosis of GPA or MPA. Widely accepted diagnostic criteria, as opposed to classification criteria or definitions, have not been developed for GPA and MPA.
* For diagnosis of GPA, meets at least 2 of the following 5 modified American College of Rheumatology (ACR) criteria:

  1. Nasal or oral inflammation with oral ulcers or nasal discharge with pus or blood
  2. Abnormal chest radiograph with nodules, fixed infiltrates, or cavities
  3. Urinary sediment with microhematuria or red cell casts
  4. Granulomatous inflammation within the wall of an artery or in the perivascular area on biopsy
  5. Antineutrophil cytoplasmic antibody (ANCA) positive by enzyme immunoassay for either PR3- or MPO-ANCA
* For diagnosis of MPA, meets the Chapel Hill Consensus Conference Definition for MPA:

  1. Necrotizing vasculitis, with few or no immune deposits, that affects small vessels (i.e., capillaries, venules, arterioles)
  2. Necrotizing arteritis involving small- and medium-sized arteries may be present
  3. Necrotizing glomerulonephritis is very common
  4. Pulmonary capillaritis often occurs
* Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

* Simultaneous diagnoses of both GPA and MPA
* Granulomatosis with polyangiitis (Churg-Strauss)
* Takayasu's arteritis
* Giant cell arteritis
* Polyarteritis nodosa
* Cogan's syndrome
* Behcet's disease
* Sarcoidosis
* Kawasaki disease
* Tuberculosis or any atypical mycobacterial infections
* Deep fungal infections
* Lymphoma, lymphomatoid granulomatosis, or any other type of cancer that mimics anti-neutrophil cytoplasmic antibody-associated vasculitis (AAVs)
* Cryoglobulinemic vasculitis
* Systemic lupus erythematosus
* Rheumatoid arthritis
* Mixed connective tissue disease or any overlapping autoimmune syndrome
B: Inclusion Criteria:

1. A new diagnosis of WG, MP or renal-limited vasculitis (RLV) (appendix 5). Patients not previously treated with cytotoxic drugs will be permitted.
2. Renal involvement attributable to active WG, MP or RLV with at least one of the following:

   * elevated serum creatinine between 150 and 500 umol/l.
   * biopsy demonstrating necrotizing glomerulonephritis.
   * red cell casts.
   * haematuria with \>30 red blood cells/high powered field and proteinuria \> 1g/24hr.
3. ANCA positivity or confirmatory histology or both (appendix 5). ANCA positivity requires a typical CANCA pattern by indirect immunofluorescence (IIF), (preferably confirmed by anti-PR3 ELISA), or the presence of PR3-ANCA or MPO-ANCA determined by ELISA, PANCA requires confirmation by anti-MPO ELISA \[6\]. (Central review of ANCA serology and histology will be performed).
4. Age 18-80 years.

Exclusion Criteria:

1. More than two weeks treatment with cyclophosphamide (CYC) or other cytotoxic drug within previous year or with oral corticosteroids (OCS) for more than 4 weeks. If the patient has received \>1.0g of methyl-prednisolone prior to the study start, discuss with trial co-ordinator.
2. Co-existence of another multisystem autoimmune disease, e.g. SLE.
3. Hepatitis Be antigen positive or Hepatitis C antibody positive.
4. Known HIV positivity (HIV testing will not be a requirement for this trial).
5. Serum creatinine \> 500umol/l (consider MEPEX trial).
6. Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence).
7. Previous malignancy (usually exclude unless agreed with trial co-ordinator).
8. Pregnancy or inadequate contraception if female.
9. Anti-GBM antibody positivity.
C: Inclusion Criteria:

* male or female patients
* aged over 18 years
* new diagnosis of microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome), satisfying ACR 1990 and/or Chapel Hill Nomenclature criteria (positive biopsy is not mandatory providing those criteria are fulfilled)
* with no factor of poor prognosis according to the French five factors score (FFS=0)
* at diagnosis or within the first 21 days following initiation of corticosteroids
* signed information and consent form
* patients covered by Health Insurance
* having had a baseline physical examination

Exclusion Criteria:

* patients with microscopic polyangiitis, polyarteritis nodosa or eosinophilic granulomatosis with polyangiitis (Churg Strauss syndrome) with one or more factor(s) of poor prognosis according to the French five factors score (FFS ≥ 1)
* patients with polyarteritis nodosa with ANCA, not satisfying the criteria for microscopic polyangiitis
* patients with clinically overt alveolar hemorrhage or respiratory distress syndrome
* patient treated with corticosteroids for more than 15 days or already receiving another immunosuppressant
* relapsing vasculitis
* other vasculitis, especially secondary vasculitides
* vasculitis secondary or associated with a viral infection, such as hepatitis B or C virus, or HIV
* malignancy
* pregnancy and breast feeding,women of child-bearing age not willing or with contra-indication to receive contraception
* contra-indication to any of the study agents
* need to continue allopurinol for those patients taking allopurinol
* consent deny or inability to receive information and give consent
* participation in another concomitant therapeutic trial
* no affiliation to any of the general French health care system
D: Key Inclusion Criteria:

* Clinical diagnosis Wegener's granulomatosis or microscopic polyangiitis by Chapel Hill criteria.
* Disease flare in the past 26 weeks requiring treatment with high dose corticosteroids and 1 of the following medications: rituximab, oral cyclophosphamide OR IV cyclophosphamide.
* Tested positive for anti-proteinase 3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies at any time prior to enrollment.
* Achieve remission no more than 26 weeks after first dose of induction treatment. Remission is defined as a Birmingham Vasculitis Activity (BVAS) score of 0 and receiving less than 10 mg/day of oral prednisone (or equivalent) on 2 consecutive visits 21 to 35 days apart.
* Maintenance therapy on this study must start no more than 2 weeks after confirmation of remission.

Key Exclusion Criteria:

* Pregnant or nursing.
* Receipt of a B cell targeted therapy (other than rituximab) at anytime
* Receipt of an investigational biological agent within the past 60 days.
* Required management of acute or chronic infections within the past 60 days.
* Current drug or alcohol abuse or dependence.
* Current or past positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
* History of severe allergic reaction to contrast agents or biological medicines.

Answer: D