A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis

Inclusion Criteria

• Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
• Age and gender: Male or female subjects age 18 years or older.
• EGPA diagnosis: subjects who have been diagnosed with EGPA for at least 6 months based on the history or presence of: asthma plus eosinophilia (>1.0x10^9/Liter and/or >10% of leucocytes) plus at least two of the following additional features of EGPA; a biopsy showing histopathological evidence of eosinophilic vasculitis, or perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation; neuropathy, mono or poly (motor deficit or nerve conduction abnormality); pulmonary infiltrates, non-fixed; sino-nasal abnormality; cardiomyopathy (established by echocardiography or Magnetic Resonance Imaging); glomerulonephritis (haematuria, red cell casts, proteinuria); alveolar haemorrhage (by bronchoalveolar lavage); palpable purpura; anti neutrophil cytoplasmic anti-body (ANCA) positive (Myeloperoxidase or proteinease 3).
• History of relapsing OR refractory disease defined as: Relapsing disease:

Subject must have a past history of at least one confirmed EGPA relapse (i.e., requiring increase in oral corticosteroids (OCS) dose, initiation/increased dose of immunosuppressive therapy or hospitalisation) within the past 2 years which occurred at least 12 weeks prior to Screening (Visit 1) whilst receiving a dose of prednisolone (or equivalent) of >=7.5 milligram per day (mg/day). Refractory disease: Either: Failure to attain remission (BVAS=0 and OCS dose =4x10^9/Liter (tested at the local laboratory, if necessary) prior to randomisation. b) Subjects who have received a methotrexate, azathioprine, or mycophenolate mofetil induction regimen may be included if on a stable dose for at least 4 weeks prior to Baseline (Visit 2). c) Subjects who have received an induction regimen comprising corticosteroids alone may be included only if they have failed to attain remission after 3 months of treatment AND the corticosteroid dose is >=15 mg/day prednisolone or equivalent for the 4 weeks prior to Baseline (Visit 2). Or: Within 6 months prior to Screening (Visit 1), recurrence of symptoms of EGPA (not necessarily meeting the protocol definition of relapse) whilst tapering OCS, occurring at any dose level >=7.5 mg/day prednisolone or equivalent.

• Corticosteroid therapy: Subject must be on a stable dose of oral prednisolone or prednisone of >=7.5 mg/day (but not >50 mg/day) for at least 4 weeks prior to Baseline (Visit 2).
• Immunosuppressive therapy: If receiving immunosuppressive therapy (excluding cyclophosphamide) the dosage must be stable for the 4 weeks prior to Baseline (Visit 2) and during the study (dose reductions for safety reasons will be permitted).
• ECG measurements: QTc(F) 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin 5.8 gram per deciliter (g/dL) (>513 micromole per liter [µmol/L]) within 3 months prior to Screening (Visit 1).
• Life-threatening EGPA: Imminently life-threatening EGPA disease defined as any of the following within 3 months prior to Screening (Visit 1); Intensive care required; Severe alveolar haemorrhage or haemoptysis requiring transfusion or ventilation or haemoglobin 2 g/dL (>20 g/L) over a 48 hour period due to alveolar haemorrhage; Rapidly progressive glomerulonephritis (RPGN) with creatinine > 2.5 milligram per deciliter (mg/dL) (>221 µmol/L) or rise in creatinine > 2 mg/dL (>177 µmol/L) over a 48 hour period; Severe gastrointestinal (GI) involvement, e.g., gangrene, bleeding requiring surgery; Severe central nervous system (CNS) involvement; Severe cardiac involvement, e.g., life-threatening arrhythmia, cardiac failure: ejection fraction 50 mg/day prednisolone/prednis