Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations

Inclusion Criteria: 1. Provision of informed consent 2. Age 40 to 85 years 3. Male and/or female. 4. Current or former smoker with a tobacco history of ≥10 pack-years. 5. History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC\<0.70 and FEV1 ≤65% of predicted normal value. 6. Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment. 1. Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization. 2. Hospitalization is defined as an inpatient admission ≥24 hours 3. Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD. 4. At least one qualifying COPD exacerbation should occur while on stable uninterrupted triple therapy prior to enrolment. 7. Documented use of triple (ICS/LABA/LAMA) background therapy for COPD for ≥3 months immediately prior to enrollment. 1. Treatment with at least double inhaled therapy containing ICS (e.g. ICS/LABA or ICS/LAMA) for the remaining of 52 weeks prior to enrolment. Use of LABA/LAMA is allowed if ICS cannot be tolerated. 2. ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily. 3. Total cumulative duration of not being on double or triple background therapy must not exceed 2 months. 4. Stable therapy/doses for the last 3 months prior to randomization. 8. Blood eosinophil count ≥300/μL at screening and documented historical eosinophil count of ≥150/μL within 52 weeks of enrollment (or repeated testing during run-in). 9. CAT total score ≥15 at Visit 1. 10. Negative pregnancy test for females of childbearing potential (WOCBP) at Visit 1. 11. Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control from enrollment throughout the study and within 12 weeks after last dose of IP. Women not of childbearing potential are defined as women who are either permanently sterilized or postmenopausal (confirmed by FSH test for women \<50 years). Exclusion Criteria: 1. Clinically important pulmonary disease other than COPD 2. Current diagnosis of asthma, prior history of asthma or asthma-COPD overlap according to GINA/GOLD. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18. 3. 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. 4. Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts. 5. Any unstable disorder that could affect patient safety, study findings or the patient's ability to complete the study. 6. Any clinically significant abnormal findings in physical examination, vital signs, ECG, laboratory tests could affect patient safety, study findings or the patient's ability to complete the study. 7. Cor pulmonale and/or right ventricular failure. 8. Long-term treatment with oxygen \>4.0 L/min and/or oxyhemoglobin saturation \<89% while breathing supplemental oxygen. 9. Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed. 10. Known immunodeficiency disorder, including positive HIV-1/2 testing. 11. Active liver disease. Chronic stable hepatitis B and C (including positive HBsAg or hepatitis C antibody testing), or other stable chronic liver disease are acceptable. 12. ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during the run-in period. 13. Helminth parasitic infection within 24 weeks prior to enrollment, not treated or failed to respond to standard of care therapy. 14. Alcohol or drug abuse within the past year, which may compromise the study data. 15. 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. 16. 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 enrollment. Evaluation will be according to the local standard of care. 17. Participation, or planned participation, in intensive COPD rehabilitation program (maintenance phase of a rehabilitation is allowed). 18. History of surgical or endoscopic lung volume reduction within the 6 months prior to enrollment. History of partial or total lung resection (single lobe or segmentectomy is acceptable). 19. Scheduled major surgical procedure during the study. Minor elective procedures are allowed. 20. History of anaphylaxis to any biologic therapy or vaccine. 21. Receipt of blood products or immunoglobulins within 30 days prior to randomization. 22. Receipt of marketed or investigational biologic product within 4 months or 5 half-lives prior to randomization, whichever is longer. Exception: Patients on stable therapy for 3 months before randomization who intend to stay on treatment throughout the study with marketed biologic products that are not likely to interfere with the safety assessment and/or efficacy of benralizumab, for example, for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, cardiovascular, or metabolic diseases, can participate in the study. 23. Receipt of live attenuated vaccines 30 days prior to randomization. 24. Chronic use of immunosuppressive medication or expected need for chronic use during the study. 25. Chronic use of antibiotics if duration of treatment is \<9 months prior to randomization. Chronic macrolide or other antibiotic therapy is allowed provided the patient has been on stable dose/regimen for ≥9 months prior to randomization and has had ≥2 COPD exacerbations while on stable therapy. 26. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to enrollment. 27. Receipt of benralizumab within 12 months prior to enrollment. 28. Known history of allergy or reaction to any component of the IP formulation.