Efficacy and Safety of Depemokimab Compared With Mepolizumab in Adults With Relapsing or Refractory Eosinophilic Granulomatosis With Polyangiitis (EGPA)

Inclusion Criteria:

• Participant (male or female) must be 18 years of age or older at the time of signingthe informed consent.

• Participants who are >=40 kilogram at Screening Visit 1.

• Participants with a documented diagnosis of EGPA for at least 6 months based on thehistory or presence of: asthma plus eosinophilia defined as >1.0*10^9/Liter (L)and/or >10 percentage (%) of leucocytes plus at least 2 of the following additionalfeatures of EGPA: a biopsy showing histopathological evidence of eosinophilicvasculitis, or perivascular eosinophilic infiltration, or eosinophil-richgranulomatous inflammation, neuropathy, mono or poly (motor deficit or nerveconduction abnormality), pulmonary infiltrates, non-fixed, sino-nasal abnormality,cardiomyopathy (established by echocardiography or magnetic resonance imaging),glomerulonephritis (hematuria, red cell casts, proteinuria), alveolar hemorrhage (bybronchoalveolar lavage), palpable purpura, anti-neutrophil cytoplasmic antibodiespositive Myeloperoxidase or Proteinase 3.

• History of relapsing OR refractory disease.

• Participants must be on a stable dose of oral prednisolone or prednisone of >=7.5mg/day (but not >50 mg/day) for at least 4 weeks prior to Baseline (Visit 2).

• If participants receiving immunosuppressive therapy (excluding cyclophosphamide) thedosage must be stable for the 4 weeks prior to Baseline (Visit 2) and during thestudy.

• A female participant is eligible to participate if she is not pregnant orbreastfeeding, and one of the following conditions applies: Is a woman ofnon-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP)and using a contraceptive method that is highly effective, with a failure rate of <1%.

• Capable of giving signed informed consent

Exclusion Criteria:

• Participants diagnosed with granulomatosis with polyangiitis; previously known asWegener's granulomatosis or microscopic polyangiitis.

• Participants with organ-threatening EGPA as per EULAR criteria,

• Imminently life-threatening EGPA disease within 3 months prior to Screening (Visit 1).

• A current malignancy or previous history of cancer in remission for less than 12months prior to Screening.

• Participants with alanine aminotransferase >2upper limit of normal (ULN) or ifparticipant is on background methotrexate or azathioprine >3ULN, aspartateaminotransferase >2ULN or if participant is on background methotrexate orazathioprine >3ULN, alkaline phosphatase >=2.0ULN, total bilirubin >1.5ULN (isolated bilirubin >1.5*ULN is acceptable if bilirubin is fractionated and directbilirubin <35%), Cirrhosis or current unstable liver or biliary disease perinvestigator assessment.

• Participants who have severe or clinically significant cardiovascular diseaseuncontrolled with standard treatment.

• Participants who have known, pre-existing, clinically significant systemabnormalities that are not associated with EGPA and are uncontrolled with standardtreatment.

• Clinically significant abnormality in the hematological, biochemical or urinalysisscreen at Visit 1.

• Chronic or ongoing active infectious disease requiring systemic treatment.

• Participants with a known, pre-existing parasitic infestation within 6 months priorto Screening Visit 1.

• A known immunodeficiency (e.g. human immunodeficiency virus [HIV]).

• Participants that, according to the investigator's medical judgment, are likely tohave active coronavirus disease 2019 (COVID-19) infection. Participants with knownCOVID-19 positive contacts within the past 14 days must be excluded for at least 14days following the exposure during which the participant must remain symptom-free.

• Participants with a known allergy or intolerance to a monoclonal antibody orbiologic therapy or any of the excipients of the investigational products.

• Participants who have a previous documented failure with anti-Interleukin-5 /Interleukin-5 receptor therapy. Participants who have received monoclonalantibodies (mAb) and who have not undergone the required washout periods, prior toVisit 1.

• Participants receiving any of the following: Oral corticosteroids: Participantrequires an oral corticosteroid dose of >50 mg/day prednisolone/prednisone in the 4-week period prior to Baseline (Visit 2), Intravenous (IV), intramuscular orsubcutaneous (SC) corticosteroids in the 4-week period prior to Baseline (Visit 2),Omalizumab within 130 days prior to Screening (Visit 1), Cyclophosphamide (CYC):oral CYC within 4 weeks prior to Baseline (Visit 2) and IV CYC within 3 weeks priorto Baseline (Visit 2), if their total white blood cells is >=4*10^9/L (measuredusing the local laboratory if necessary), Rituximab within 12 months prior toScreening (Visit 1); in addition, the Participant must have shown recovery ofperipheral B-cell count to within the normal range, Tezepelumab and Dupilumab with awashout period of 5 half-lives prior to Screening Visit 1, IV or SC immunoglobulinwithin 6 months prior to Screening (Visit 1); For China and Japan only within 12weeks prior to Screening (Visit 1), Interferon-alpha within 6 months prior toScreening Visit 1, Anti-tumor necrosis factor therapy within 12 weeks prior toScreening Visit 1, Anti-CD52 (alemtuzumab) within 6 months prior to Screening Visit

• Participants with QT interval corrected for heart rate according to Fridericia'sformula (QTcF) >=450 milliseconds (msec) or QTcF >=480 msec for participants withBundle Branch Block in the 12-lead ECG central over-read from at Screening Visit 1.