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Provision of informed consent |
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Age 40 to 85 years |
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Male and/or female |
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Current or former smoker with a tobacco history of ≥10 pack-years |
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History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC<0.70 and FEV1 ≤65% of predicted normal value |
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Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment |
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Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization |
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Hospitalization is defined as an inpatient admission ≥24 hours |
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Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD |
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At least one qualifying COPD exacerbation should occur while on stable uninterrupted triple therapy prior to enrolment |
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Documented use of triple (ICS/LABA/LAMA) background therapy for COPD for ≥3 months |
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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 |
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immediately prior to enrollment |
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Stable therapy/doses for the last 3 months prior to randomization |
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Total cumulative duration of not being on double or triple background therapy must not exceed 2 months |
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ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily |
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Negative pregnancy test for females of childbearing potential (WOCBP) at Visit 1 |
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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 |
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Blood eosinophil count ≥300/μL at screening and documented historical eosinophil count |
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of ≥150/μL within 52 weeks of enrollment (or repeated testing during run-in) |
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CAT total score ≥15 at Visit 1 |
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Women not of childbearing potential are defined as women who are either permanently |
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sterilized or postmenopausal (confirmed by FSH test for women <50 years) |
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Clinically important pulmonary disease other than COPD
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Current diagnosis of asthma, prior history of asthma or asthma-COPD overlap according
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to GINA/GOLD. Childhood history of asthma is allowed and defined as asthma diagnosed
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Cor pulmonale and/or right ventricular failure
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and resolved before the age of 18
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Radiological findings of a respiratory disease other than COPD contributing to
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respiratory symptoms. Solitary pulmonary nodules without appropriate follow up or
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Known immunodeficiency disorder, including positive HIV-1/2 testing
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findings of acute infection
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Another pulmonary or systemic disease associated with elevated peripheral eosinophil
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counts
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Any unstable disorder that could affect patient safety, study findings or the
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Alcohol or drug abuse within the past year, which may compromise the study data
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patient's ability to complete the study
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Any clinically significant abnormal findings in physical examination, vital signs
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ECG, laboratory tests could affect patient safety, study findings or the patient's
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ability to complete the study
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Long-term treatment with oxygen >4.0 L/min and/or oxyhemoglobin saturation <89% while
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breathing supplemental oxygen
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Receipt of blood products or immunoglobulins within 30 days prior to randomization
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Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of
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History of anaphylaxis to any biologic therapy or vaccine
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CPAP for Sleep Apnea Syndrome is allowed
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Receipt of live attenuated vaccines 30 days prior to randomization
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Active liver disease. Chronic stable hepatitis B and C (including positive HBsAg or
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hepatitis C antibody testing), or other stable chronic liver disease are acceptable
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ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during
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Receipt of benralizumab within 12 months prior to enrollment
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the run-in period
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Known history of allergy or reaction to any component of the IP formulation
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Helminth parasitic infection within 24 weeks prior to enrollment, not treated or
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failed to respond to standard of care therapy
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Malignancy, current or within the past 5 years, except for adequately treated non
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invasive basal cell and squamous cell carcinoma of the skin and cervical
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carcinoma-in-situ treated with apparent success more than 1 year prior to Visit 1
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Suspected malignancy or undefined neoplasms
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Evidence of active tuberculosis, as judged by investigator. Patients with a recent
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(within 2 years) first-time or newly positive PPD or Quantiferon test need to complete
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an appropriate course of treatment before enrollment. Evaluation will be according to
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the local standard of care
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Participation, or planned participation, in intensive COPD rehabilitation program
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(maintenance phase of a rehabilitation is allowed)
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History of surgical or endoscopic lung volume reduction within the 6 months prior to
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enrollment. History of partial or total lung resection (single lobe or segmentectomy
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is acceptable)
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Scheduled major surgical procedure during the study. Minor elective procedures are
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allowed
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Receipt of any marketed or investigational biologic product within 4 months or 5
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half-lives prior to randomization, whichever is longer
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Chronic use of immunosuppressive medication or expected need for chronic use during
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the study
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Chronic use of antibiotics if duration of treatment is <9 months prior to
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randomization. Chronic macrolide or other antibiotic therapy is allowed provided the
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patient has been on stable dose/regimen for ≥9 months prior to randomization and has
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had ≥2 COPD exacerbations while on stable therapy
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Receipt of any investigational non-biologic product within 30 days or 5 half-lives
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prior to enrollment
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