Provision of informed consent.
Age 40 to 85 years.
Male and/or female.
Current or former smoker with a tobacco history of ≥ 10 pack‐years.
History of moderate to very severe COPD with a post‐bronchodilator FEV₁/FVC < 0.70 and FEV₁ ≤ 65% of predicted normal value.
Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids or hospitalisation (or both) within 52 weeks prior to enrolment. Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids or hospitalisation (or both). Hospitalisation is defined as an inpatient admission ≥ 24 hours. Previous exacerbations should be confirmed to have occurred whilst on stable triple therapy for COPD.
Documented use of triple (ICS/LABA/LAMA) background therapy for COPD throughout the year (52 weeks) prior to enrolment. ICS dose should be equivalent to ≥ 500 μg of fluticasone propionate daily. Total cumulative duration of not being on triple background therapy must not exceed 2 months. Stable therapy/doses for the last 3 months prior to randomisation.
Blood eosinophil count ≥ 300/μL at screening and documented historical eosinophil count of ≥ 150/μL within 52 weeks of enrolment (or repeated testing during run‐in).
CAT total score ≥ 15 at Visit 1.
Negative pregnancy test for females of childbearing potential at Visit 1.
Women of childbearing potential must agree to use a highly effective method of birth control from randomisation throughout the study and 16 weeks after last dose of IP.
Clinically important pulmonary disease other than COPD.
Current diagnosis of asthma, prior history of asthma or asthma‐COPD overlap.
Radiological findings of a respiratory disease other than COPD contributing to respiratory symptoms. Solitary pulmonary nodules without appropriate follow‐up or findings of acute infection.
Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
Any unstable disorder that could affect participant safety, study findings, or the participant's ability to complete the study.
Any clinically significant abnormal findings in physical examination, vital signs, ECG, laboratory tests that could affect participant safety, study findings, or the participant's ability to complete the study.
Cor pulmonale or right ventricular failure (or both).
Long‐term treatment with oxygen > 4.0 L/min and/or oxyhaemoglobin saturation < 89% whilst breathing supplemental oxygen.
Use of any NIPPV device. Note: use of CPAP or BiPAP for sleep apnoea syndrome is allowed.
Known immunodeficiency disorder, including positive HIV‐1/2 testing.
Active liver disease. Chronic stable hepatitis B and C (including positive HBsAg or hepatitis C antibody testing), or other stable chronic liver disease is acceptable.
ALT or AST ≥ 3 times the upper limit of normal, confirmed by repeated testing during the run‐in period.
Helminth parasitic infection within 24 weeks prior to enrolment, not treated or failed to respond to standard of care therapy.
Alcohol or drug abuse within the past year, which may compromise the study data.
Malignancy, current or within the past 5 years, except for adequately treated non‐invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma‐in‐situ treated with apparent success more than 1 year prior to Visit 1. Suspected malignancy or undefined neoplasms.
Evidence of active tuberculosis, as judged by investigator. Patients with a recent (within 2 years) first‐time or newly positive PPD or QuantiFERON test need to complete an appropriate course of treatment before enrolment. Evaluation will be according to the local standard of care.
Participation, or planned participation, in intensive COPD rehabilitation programme (maintenance phase of a rehabilitation is allowed).
History of surgical or endoscopic lung volume reduction within the 6 months prior to enrolment. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
Scheduled major surgical procedure during the study. Minor elective procedures are allowed.
History of anaphylaxis to benralizumab or any other biologic therapy.
Receipt of blood products or immunoglobulins within 30 days prior to randomisation.
Receipt of any marketed or investigational biologic product within 4 months or 5 half‐lives prior to randomisation, whichever is longer.
Receipt of live attenuated vaccines 30 days prior to randomisation.
Chronic use of immunosuppressive medication or expected need for chronic use during the study.
Chronic use of antibiotics if duration of treatment is < 9 months prior to randomisation. Chronic macrolide or other antibiotic therapy is allowed provided the patient has been on stable dose/regimen for ≥ 9 months prior to randomisation and has had ≥ 2 COPD exacerbations whilst on stable therapy.
Receipt of any investigational non‐biologic product within 30 days or 5 half‐lives prior to enrolment.
Receipt of benralizumab within 12 months prior to enrolment.
Known history of allergy or reaction to any component of the IP formulation.
