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

AstraZeneca1,656 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

1,656

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

PlaceboDRUG

Placebo 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:1.Informed consent. 2.Subjects 40-85 y.o. 3.Moderate to very severe COPD with Post Bronchodilator (BD) FEV1\>20% and ≤65%. 4.≥2 moderate or ≥1 severe COPD exacerbation(s) required treatment or hospitalization within 2-52 weeks prior to Visit1. 5. Modified Medical Research Council (mMRC) score ≥1 at Visit 1. 6.Treatment with double or triple therapy throughout the year prior to Visit 1, constant 2 weeks prior to Visit 1. 7.Tobacco history of ≥10 pack-years. 8.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. 9.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. 10.Compliance with maintenance therapy during run-in ≥70%. 11. 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levels.When any eosinophil cohort is full, subjects in the completed cohort will not be randomised and will be withdrawn from the study.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: 1. Clinically important pulmonary disease other than COPD or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts. 2\. 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. 3\. 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. 4\. 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. 5\. Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 2 weeks prior to Visit1or during the enrolment and run-in period. 6\. Pneumonia within 8 weeks prior to Visit1 or during the enrolment and run-in period. 7\. Pregnant, breastfeeding, or lactating women. 8. Risk factors for pneumonia 9. History of anaphylaxis to any other biologic therapy. 10. Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right ventricular failure. 11\. Use of immunosuppressive medication within 2 weeks prior to Visit1 and/or during the enrolment and run-in period. 12\. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit 1. 13\. Evidence of active tuberculosis (TB) without an appropriate course of treatment. 14\. 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). 15\. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines. 16\. Previous treatment with benralizumab. 17. Helminth parasitic infection diagnosed within 24 weeks prior to Visit 1.

Locations (407)

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: From first IP to week 56

Secondary Outcomes

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

Time frame: From first IP to 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

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

Data from ClinicalTrials.gov

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Research Site

Andalusia, Alabama, United States

Research Site

Birmingham, Alabama, United States

Research Site

Birmingham, Alabama, United States

Research Site

Dothan, Alabama, United States

Research Site

Jasper, Alabama, United States

Research Site

Little Rock, Arkansas, United States

Research Site

Beverly Hills, California, United States

Research Site

Gold River, California, United States

Research Site

Huntington Beach, California, United States

Research Site

Huntington Park, California, United States

...and 397 more locations

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.

Time frame: First IP up to Week 56

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

CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. Score ranges from 0 to 40 with higher scores indicative of greater COPD impact on health status.

Time frame: First IP up to Week 56

Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL

The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.

Time frame: First IP up to Week 56

Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL

The number of rescue medication inhalations and nebulizer treatments taken are recorded by the patient in the eDiary twice daily. Total rescue medication use is the sum of daytime and night-time use.

Time frame: First IP up to Week 56

Mean Change From Baseline in Proportion of Nights Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL

Change from baseline to week 56 in proportion of nights awakenings due to respiratory symptoms.

Time frame: First IP up to Week 56

Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL