efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory eosinophilic granulomatosis with polyangiitis (egpa)

Conditions: Eosinophilic Granulomatosis With Polyangiitis

Summary: this study aims to investigate the efficacy and safety of depemokimab compared with mepolizumab in adults with relapsing or refractory egpa receiving soc therapy.


Eligibility criteria:
inclusion criteria: * participant (male or female) must be 18 years of age or older at the time of signing the 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 the history 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 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 (hematuria, red cell casts, proteinuria), alveolar hemorrhage (by bronchoalveolar lavage), palpable purpura, anti-neutrophil cytoplasmic antibodies positive myeloperoxidase or proteinase 3. * history of relapsing or refractory disease. * participants 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). * if participants receiving immunosuppressive therapy (excluding cyclophosphamide) the dosage must be stable for the 4 weeks prior to baseline (visit 2) and during the study. * a female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: is a woman of non-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 as wegener'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 12 months prior to screening. * participants with alanine aminotransferase \>2\*upper limit of normal (uln) or if participant is on background methotrexate or azathioprine \>3\*uln, aspartate aminotransferase \>2\*uln or if participant is on background methotrexate or azathioprine \>3\*uln, alkaline phosphatase \>=2.0\*uln, total bilirubin \>1.5\*uln (isolated bilirubin \>1.5\*uln is acceptable if bilirubin is fractionated and direct bilirubin \<35%), cirrhosis or current unstable liver or biliary disease per investigator assessment. * participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. * participants who have known, pre-existing, clinically significant system abnormalities that are not associated with egpa and are uncontrolled with standard treatment. * clinically significant abnormality in the hematological, biochemical or urinalysis screen at visit 1. * chronic or ongoing active infectious disease requiring systemic treatment. * participants with a known, pre-existing parasitic infestation within 6 months prior to screening visit 1. * a known immunodeficiency (e.g. human immunodeficiency virus \[hiv\]). * participants that, according to the investigator's medical judgment, are likely to have active coronavirus disease 2019 (covid-19) infection. participants with known covid-19 positive contacts within the past 14 days must be excluded for at least 14 days following the exposure during which the participant must remain symptom-free. * participants with a known allergy or intolerance to a monoclonal antibody or biologic 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 monoclonal antibodies (mab) and who have not undergone the required washout periods, prior to visit 1. * participants receiving any of the following: oral corticosteroids: participant requires an oral corticosteroid dose of \>50 mg/day prednisolone/prednisone in the 4-week period prior to baseline (visit 2), intravenous (iv), intramuscular or subcutaneous (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 prior to baseline (visit 2), if their total white blood cells is \>=4\*10\^9/l (measured using the local laboratory if necessary), rituximab within 12 months prior to screening (visit 1); in addition, the participant must have shown recovery of peripheral b-cell count to within the normal range, tezepelumab and dupilumab with a washout period of 5 half-lives prior to screening visit 1, iv or sc immunoglobulin within 6 months prior to screening (visit 1); for china and japan only within 12 weeks prior to screening (visit 1), interferon-alpha within 6 months prior to screening visit 1, anti-tumor necrosis factor therapy within 12 weeks prior to screening visit 1, anti-cd52 (alemtuzumab) within 6 months prior to screening visit 1. * participants with qt interval corrected for heart rate according to fridericia's formula (qtcf) \>=450 milliseconds (msec) or qtcf \>=480 msec for participants with bundle branch block in the 12-lead ecg central over-read from at screening visit 1.

Keywords: depemokimab mepolizumab eosinophilic granulomatosis with polyangiitis