Clinical Trials

Inclusion Criteria:

• Participant (male or female) must be 18 years or older at the time of signing the informed consent.
• Participants who are ≥ 40 kg at Screening Visit 1.
• EGPA diagnosis: Participants who have been diagnosed with EGPA for at least 6 months based on the history or presence of: asthma plus eosinophilia [Jennette, 2013] defined in this study as > 1.0x10^9/L and/or > 10% 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 [MRI]);
  • glomerulonephritis (haematuria, red cell casts, proteinuria);
  • alveolar haemorrhage (by bronchoalveolar lavage);
  • palpable purpura;
  • ANCA positive Myeloperoxidase (MPO) or Proteinase 3 (PR3).
• History of relapsing OR refractory disease defined as:
  • Relapsing disease: Participants must have a history of at least one confirmed EGPA relapse (i.e., requiring increase in OCS dose, initiation/increased dose of immunosuppressive therapy or inpatient hospitalisation due to EGPA) within the past 2 years. EGPA relapse should have occurred at least 12 weeks or more prior to Screening (Visit 1) whilst receiving a dose of prednisolone (or equivalent of) ≥ 7.5 mg/day;
  • Refractory disease: Defined as either failure to attain remission (BVAS=0 and OCS dose ≤ 7.5 mg/day prednisolone or equivalent) within the last 6 months prior to Screening Visit 1 and following induction treatment with a standard OCS regimen, administered for at least 3 months OR participants with recurrence of EGPA symptoms within 6 months prior to Screening (Visit 1) whilst tapering OCS and occurring at any dose level ≥7.5 mg/day prednisolone or equivalent.
    • NOTE: Recurrent symptoms of EGPA do not necessarily need to meet the protocol definition of relapse.
• Corticosteroid therapy: 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).
• 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.
• 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 nonchildbearing 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%, from at least 14 days prior to the first dose of study intervention until the following durations (whichever is greater)
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

• GPA or MPA: Diagnosed with granulomatosis with polyangiitis (GPA; previously known as Wegener’s granulomatosis) or microscopic polyangiitis (MPA).
• EULAR defined organ-threatening EGPA: Organ-threatening EGPA as per EULAR criteria, i.e., organ failure due to active vasculitis, creatinine > 5.8 g/dL (> 513 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).
• Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening. Participants that had localised carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded).
• Liver Disease: Alanine aminotransferase (ALT) > 2 x upper limit of normal (ULN) or if participant is on background methotrexate or azathioprine > 3 x ULN, AST > 2 x ULN or if participant is on background methotrexate or azathioprine > 3 x ULN, Alkaline Phosphatase ≥ 2.0 x ULN , Total bilirubin > 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%), Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice.
• Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment including but not limited to: Known ejection fraction of < 20%, OR Severe heart failure that meets New York Heart Association Class IV, OR Hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR Myocardial infarction or angina diagnosed less than 3 months prior to or at Screening Visit 1 ORUncontrolled life threatening arrythmia within 3 months prior to or at Screening Visit 1).
• Other Concurrent Medical Conditions: Participants who have known, pre‑existing, clinically significant cardiac, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory or any other system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment.
• Laboratory abnormality: Evidence of clinically significant abnormality in the haematological, biochemical or urinalysis screen at Visit 1, as judged by the investigator.
• Infectious disease: Chronic or ongoing active infectious disease requiring systemic treatment.
• Parasitic infection: Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.
• Immunodeficiency: A known immunodeficiency (e.g., human immunodeficiency virus – HIV), other than that explained by the use of OCS or other immunosuppressants taken as therapy for EGPA.
• COVID-19: Participants that, according to the investigator's medical judgment, are likely to have active 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.
• Hypersensitivity: Participants with a known allergy or intolerance to a monoclonal antibody or biologic therapy or any of the excipients of the investigational products.
• Monoclonal antibodies targeting IL-5/5R: Participants who have a previous documented failure with anti-IL-5/5R therapy.
• Participants who have received treatment with investigational drug within the past 30 days or 5 terminal phase half-lives of the drug whichever is longer, prior to Visit 1 (this also includes investigational formulations of marketed products).  Participants who are currently participating in any other interventional clinical study.
• Other prohibited medications: 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, intramuscular or SC corticosteroids in the 4-week period prior to Baseline (Visit 2);
  • Omalizumab within 130 days prior to Screening (Visit 1);
  • Cyclophosphamide:  oral CYC within 4 weeks prior to Baseline (Visit 2) and IV CYC within 3 weeks prior to Baseline (Visit 2), if their total WBC is ≥ 4 x10^9/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;
  • 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-α within 6 months prior to Screening Visit 1;
  • Anti-TNF therapy within 12 weeks prior to Screening Visit 1;
  • Anti-CD52 (alemtuzumab) within 6 months prior to Screening Visit 1.
• Previous participation: Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 6 months prior to Screening Visit 1.
• ECG Assessment: QTcF ≥ 450 msec or QTcF ≥ 480 msec for participants with Bundle Branch Block at Screening Visit 1.
• Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
• Pregnancy: Participants who are pregnant or breastfeeding. Participants should not be enrolled if they plan to become pregnant during the time of study participation.
• Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.

Eligibility last updated 2/17/22. Questions regarding updates should be directed to the study team contact.