A Study to Evaluate the Effectiveness and Safety of Benralizumab Compared to Mepolizumab to Treat Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Overview

About this study

The purpose of this study is to evaluate the effectiveness and safety of Benralizumab compared to Mepolizumab to treat Eosinophilic Granulomatosis with Polyangiitis (EGPA) in patients receiving standard of care (SOC) therapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Male or female subjects age 18 years or older.
  • Provision of signed and dated, written ICF prior to any mandatory study specific procedures, sampling, and analyses.
  • EGPA diagnosis based on history or presence asthma and eosinophilia (> 1.0x10^9/L and/or >10% of leucocytes) and at least 2 of; biopsy with eosinophilic vasculitis or perivascular/granulomatous inflammation; mono-or polyneuropathy, non-fixed pulmonary infiltrates, sino-nasal abnormality; cardiomyopathy; glomerulonephritis; alveolar haemorrhage; palpable purpura; anti neutrophil cytoplasmic anti-body (ANCA) positivity (Myeloperoxidase or proteinease 3).
  • History of relapsing (at least 1 confirmed EGPA relapse within last 2 years and > 12 weeks prior to screening, or refractory (failure to attain remission, defined as BVAS=0 and oral corticosteroid (OCS) dose ≤ 7.5 mg/day of prednisolone or equivalent, following standard induction regimen for at least 3 months and within 6 months prior to screening, or recurrence of symptoms upon OCS tapering at any dose of ≥ 7.5 mg/day prednisolone or equivalent. If induction with glucocorticoidsalone, patient must have failed to attain remission after 3 months and the glucocorticoid dose must be ≥ 15 mg/day prednisolone or equivalent for the 4 weeks prior to randomization.
  • Must be on a stable dose of oral prednisolone or prednisone of ≥ 7.5 mg/day (but not > 50mg/day) for at least 4 weeks prior to randomization.
  • If receiving immunosuppressive therapy (excluding cyclophosphamide) the dose must be stable for the 4 weeks prior to randomization and during the study (dose reductions for safety reasons will be permitted).
  • QTc(F) < 450 msec or QTc(F) < 480 msec for patients with bundle branch block.
  • Females of childbearing potential must use an acceptable method of birth control from signing the informed consent until 4 months after the last study drug administration.

Exclusion Criteria:

  • Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).
  • Organ-threatening EGPA: organ-threatening EGPA as per the European League against Rheumatism criteria (Yates et al 2016); i.e., organ failure due to active vasculitis, creatinine > 5.8 mg/dL (> 513 μmol/L) within 3 months prior to screening (Visit 1) and through randomisation (Visit 2).
  • Life-threatening EGPA: imminently life-threatening EGPA disease defined as any of the following within 3 months prior to screening (Visit 1) and through randomisation (Visit 2).
  • Currently pregnant or breastfeeding, or planning to become pregnant during study participation.
    • Intensive care required;
    • Severe alveolar haemorrhage or haemoptysis requiring transfusion or ventilation or haemoglobin < 8 g/dL (< 80 g/L) or drop in haemoglobin > 2 g/dL (> 20 g/L) over a 48-hour period due to alveolar haemorrhage;
    • Rapidly progressive glomerulonephritis with creatinine > 2.5 mg/dL (> 221 μmol/L) or rise in creatinine > 2 mg/dL (> 177 μmol/L) over a 48-hour period;
    • Severe gastrointestinal involvement, for example, gangrene, bleeding requiring surgery;
    • Severe central nervous system involvement;
    • Severe cardiac involvement, for example, life-threatening arrhythmia, cardiac failure: ejection fraction < 20%, NYHA Class III/IV (NYHA 2012), acute myocardial infarction.
  • Patients who have had basal cell carcinoma, localised squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to screening (Visit 1).
  • Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)
  • Patients who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment including but not limited to:
    • Known ejection fraction < 30%, OR
    • Severe heart failure that meet NYHA Class IV (NYHA 2012), OR
    • Hospitalised in the 12 months prior to screening (Visit 1) for severe heart failure meeting NYHA Class III (NYHA 2012), OR
    • Angina diagnosed within 3 months prior to screening (Visit 1) and through randomisation (Visit 2).
  • Chronic or ongoing active infectious disease requiring systemic treatment.
  • A helminth parasitic infection diagnosed within 6 months prior to screening (Visit 1) and through randomisation (Visit 2) that has not been treated with or has failed to respond to standard of care therapy.
  • Chronic stable hepatitis B and C (including positive testing for HBsAg or hepatitis C antibody), or other stable chronic liver disease are acceptable if patient otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.
  • A history of known immunodeficiency disorder including a positive HIV test.
  • History of known allergy, intolerance, or anaphylaxis to any biologic therapy or vaccine.
  • Known history of allergy or reaction to any component of the IP formulation.
  • Patients who have known, preexisting, clinically significant endocrine, autoimmune, metabolic, neurologic, renal, gastrointestinal, hepatic, haematological, respiratory or any other system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk, because of his/her participation in the study, or may influence the results of the study, or the patients’ ability to complete entire duration of the study.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
  • Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
  • Previous randomisation in the present study.
  • Participant is currently participating in any other interventional clinical study.
  • For women only: Currently pregnant, breastfeeding, or lactating. Patients should not be enrolled if they plan to become pregnant during the time of study participation. A serum pregnancy test will be done for WOCBP at screening (Visit 1) and a urine pregnancy test must be performed for WOCBP at each treatment visit prior to IP administration. A positive urine test result must be confirmed with a serum pregnancy test, before proceeding with further IP dosing. If serum test is positive, the patient should be excluded.
  • Other laboratory parameter exclusions at screening (Visit 1) and on repeat testing (if applicable) prior to Visit 2: 
    • Creatinine > 2.5 mg/dL (221 µmol/L);
    • WBC < 4 × 10^9 /L;
    • Platelet count < 120000/mm^3;
    • Haemoglobin < 8 g/dL (< 80 g/L).
  • Alcohol/substance abuse: a history (or suspected history) or alcohol misuse or substance abuse within 2 years prior to screening (Visit 1).
  • Other investigational non-biologic product: receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to screening (Visit 1), whichever is longer.
  • Adherence: patients who have known evidence of lack of adherence to prescribed medications and/or ability to follow physician's recommendations.
  • ALT or AST level ≥ 3 times the ULN confirmed during screening period, confirmed by repeated testing (if applicable) during screening period. Transient increase of AST/ALT level that resolves by the time of randomisation is acceptable if, in the Investigator’s opinion, the patient does not have an active liver disease and meets other eligibility criteria.
  • Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, which in the opinion of the Investigator, may put the patient at risk, because of his/her participation in the study, or may influence the results of the study, or the patients’ ability to complete entire duration of the study. Any other medical illness that precludes study involvement.
  • Receipt of blood products within 30 days prior to screening (Visit 1).
  • Receipt of live attenuated vaccines 30 days prior to screening (Visit 1).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Ulrich Specks, M.D.

Open for enrollment

Contact information:

Samantha Hughes CCRP

(507) 266-1026

Hughes.Samantha@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20490392

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