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

AstraZeneca2,255 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

2,255

Conditions

Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Interventions

Benralizumab Arm ADRUG

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Benralizumab Arm BDRUG

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Benralizumab Arm CDRUG

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Eligibility

Sex: ALLMin age: 40 YearsMax age: 85 Years

Medical Language ↔ Plain English

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levels.When any eosinophil cohort is full, subjects in the completed cohort will not be randomised and will be withdrawn from the study.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.

Locations (356)

Outcomes

Primary Outcomes

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL

A COPD exacerbation is defined by symptomatic worsening of COPD requiring: * Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or * Use of antibiotics; and/or * An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.

Time frame: Immediately following the first IP dose through week 56

Secondary Outcomes

Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL

Time frame: Immediately following the first IP dose through week 56

Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL

Pre-bronchodilator FEV1 (L) is collected at Weeks 0, 4, 8, 16, 24, 32, 40, 48, and 56. Baseline is the last non-missing value with quality (acceptable or borderline quality grade) prior to the first dose of study treatment.

Time frame: First IP up to end of treatment Week 56

Data from ClinicalTrials.gov

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Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Research Site

Birmingham, Alabama, United States

Research Site

Gulf Shores, Alabama, United States

Research Site

Montgomery, Alabama, United States

Research Site

Flagstaff, Arizona, United States

Research Site

Phoenix, Arizona, United States

Research Site

Anaheim, California, United States

Research Site

Arcadia, California, United States

Research Site

Bakersfield, California, United States

Research Site

Fresno, California, United States

Research Site

Fullerton, California, United States

...and 346 more locations

Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL

SGRQ is from 50-item PRO instrument. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0 indicates the best possible health status.