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

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.