Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History
Condition: Moderate to Very Severe Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Benralizumab Arm A; Benralizumab Arm B; Benralizumab Arm C; Placebo
Intervention description: Benralizumab subcutaneously on study week 0 until study week 48 inclusive; Benralizumab subcutaneously on study week 0 until study week 48 inclusive; Benralizumab subcutaneously on study week 0 until study week 48 inclusive; Benralizumab subcutaneously on study week 0 until study week 48 inclusive
Intervention MeSH terms: Benralizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 2255.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Obstructive Lung Diseases; Chronic Obstructive Pulmonary Disease; Lung Disease; Bronchial Diseases; COPD Exacerbation; Respiratory Tract Diseases

Summary:

      The purpose of the study is to determine if benralizumab reduces COPD exacerbation rate in
      symptomatic patients with moderate to very severe COPD who are receiving standard of care
      therapies.
    

Eligibility criteria:

        Inclusion Criteria:.

          -  Informed consent.

          -  Subjects 40-85 y.o.

          -  Moderate to very severe COPD with Post Bronchodilator (BD) FEV1>20% and ≤65%.

             -≥2 moderate or ≥1 severe COPD exacerbation(s) required treatment or hospitalization
             within 2-52 weeks prior to Visit1.

          -  Modified Medical Research Council (mMRC) score ≥1 at Visit 1.

          -  Treatment with double or triple therapy throughout the year prior to Visit 1, constant
             2 weeks prior to Visit 1.

          -  Tobacco history of ≥10 pack-years.

          -  Women of childbearing potential must use a highly effective form of birth control from
             Visit 1 until 16 weeks after their last dose, and negative serum pregnancy test result
             at Visit 1.

          -  Male subjects who are sexually active must be surgically sterile one year prior to
             Visit 1 or use an adequate method of contraception from the first Investigational
             Product (IP) dose until 16 weeks after their last dose.

          -  Compliance with maintenance therapy during run-in ≥70%.

          -  Blood eosinophils due to subject's stratification and cap for blood eosinophil
             levels.When any eosinophil cohort is full, subjects in the completed cohort will not
             be randomised and will be withdrawn from the study.

        Exclusion criteria:

          -  Clinically important pulmonary disease other than COPD or another diagnosed pulmonary
             or systemic disease associated with elevated peripheral eosinophil counts.

          -  Any disorder or major physical impairment that is not stable by Investigator opinion
             and/or could affect: - subject safety-study findings or their interpretation or
             subject's ability to complete the entire study duration.

          -  Unstable ischemic heart disease, arrhythmia, cardiomyopathy, or other relevant
             cardiovascular disorder that in Investigator's judgment may put the patient at risk or
             negatively affect the study outcome.

          -  Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for
             a COPD exacerbation within 2 weeks prior to Visit1 or during the enrolment and run-in
             period.

          -  Acute upper or lower respiratory infection requiring antibiotics within 2 weeks prior
             to Visit1 or during the enrolment and run-in period.

          -  Pneumonia within 8 weeks prior to Visit1 or during the enrolment and run-in period.

          -  Pregnant, breastfeeding, or lactating women.

          -  Risk factors for pneumonia

          -  History of anaphylaxis to any other biologic therapy.

          -  Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right
             ventricular failure.

          -  Use of immunosuppressive medication within 2 weeks prior to Visit1 and/or during the
             enrolment and run-in period.

          -  Receipt of any investigational non-biologic product within 30 days or 5 half-lives
             prior to Visit 1.

          -  Evidence of active tuberculosis (TB) without an appropriate course of treatment.

          -  Lung volume reduction surgery within the 6 months prior to Visit 1. History of partial
             or total lung resection (single lobe or segmentectomy is acceptable).

          -  Asthma as a primary or main diagnosis according to the Global Initiative for Asthma
             (GINA) guidelines or other accepted guidelines.

          -  Previous treatment with benralizumab.

          -  Helminth parasitic infection diagnosed within 24 weeks prior to Visit 1.