A Study to Evaluate the Effectiveness of MEDI-563 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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To evaluate the effect of the drug in moderate to severe Chronic Obstructive Pulmonary Disease (COPD) in Adults.

Detailed Description
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To evaluate the effect of multiple subcutaneous (SC) doses of benralizumab (MEDI 563) on the rate of moderate-to-severe annualized incidence rate of moderate or severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in adult subjects with moderate-to-severe COPD who exhibit eosinophilia (greater than or equal to [>=] 3.0 percent [%] sputum eosinophilia in the previous 12 months or at Screening) in sputum compared to placebo.

Official Title
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A Phase 2a, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of MEDI-563 in Subjects With Moderate-to-severe Chronic Obstructive Pulmonary Disease and Sputum Eosinophilia

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Other: Placebo
* Biological: Benralizumab 100 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 40-85 years at the time of Screening Written informed consent obtained from the subject prior to performing any protocol related procedures Documented history of 1 or more Annualized Incidence Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) Current smoker or ex-smoker with a tobacco history of greater than or equal to (>=) 10 pack-years Adequate contraception from screening through end of trial Able to read and write. Exclusion Criteria: Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results Pregnant, breastfeeding, or lactating women Known history of allergy or reaction to any component of the investigational product formulation History of anaphylaxis to any other biologic therapy Donation or transfusion of blood, plasma or platelets within the past 3 months prior to Screening Other significant pulmonary disease which in the opinion of the investigator or medical monitor, might compromise the interpretation of the study Fever greater than (>) 37.0 degree Centigrade (98.6 degree Fahrenheit) at Screening Receipt of any novel investigational medicinal product within 3 months before the first dose of investigational product in this study and through the end of the study Seropositive for hepatitis A, hepatitis B surface antigen, hepatitis C, or human immunodeficiency virus 1or 2 (HIV-1 or HIV 2) History of alcohol or drug abuse within the past year that required treatment that the investigator felt or medical monitor felt would compromise the study data interpretation Past or current malignancy within the past 5 years except 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 Screening Subjects participating in, or scheduled for, an intensive COPD rehabilitation program (subjects who are in the maintenance phase of a rehabilitation program are eligible to take part) Current diagnosis of asthma according to Global Initiative for Asthma guidelines Previous treatment with MEDI-563.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo matched to benralizumab (MEDI-563) injection subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks for the next 5 doses (Day 1, 29, 57, 113, 169, 225, 281 and 337). | Other: Placebo<br>* Placebo matched to benralizumab (MEDI-563) injection subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks for the next 5 doses (Day 1, 29, 57, 113, 169, 225, 281 and 337).<br>|
| Experimental: Benralizumab 100 mg<br>Benralizumab (MEDI-563) 100 mg injection subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks for the next 5 doses (Day 1, 29, 57, 113, 169, 225, 281 and 337). | Biological: Benralizumab 100 mg<br>* Benralizumab (MEDI-563) 100 mg injection subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks for the next 5 doses (Day 1, 29, 57, 113, 169, 225, 281 and 337).<br>* Other names: MEDI-563;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Incidence Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | An AECOPD is defined as worsening of two or more major symptoms or one major and one minor symptom for two or more consecutive days. Annualized Incidence Rate of Moderate or Severe AECOPD was assessed based on AECOPD data up to Day 393 (Rate = total number of moderate or severe AECOPD in each group/total person-year follow-up in each group). The severity of an exacerbation of COPD is defined as: a) Mild exacerbations, which require treatment with an increase in usual therapy, example (eg), increase use of short acting bronchodilators, b) Moderate exacerbations which require treatment with systemic corticosteroids, and or antibiotics and c) Severe exacerbations which require hospitalization. | Day 1 up to 393 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between administration of study drug and up to Day 561 that were absent before treatment or that worsened relative to pre-treatment state. TEAEs reported below included both SAEs and non-serious AEs. | Day 1 up to 561 | 
| Number of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | An AECOPD is defined as worsening of two or more major symptoms or one major and one minor symptom for two or more consecutive days. | Day 1 up to 393 | 
| Percentage of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | An AECOPD is defined as worsening of two or more major symptoms or one major and one minor symptom for two or more consecutive days. | Day 1 up to 393 | 
| Annual Incidence Rate of Hospitalization Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | An AECOPD is defined as worsening of two or more major symptoms or one major and one minor symptom for two or more consecutive days. Annualized Incidence Rate of hospitalization due to AECOPD was calculated as Rate = total number of hospitalizations/ total person years. | Day 1 up to 393 | 
| Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | The SGRQ is a health related quality of life questionnaire consisting of 40 items in three domains: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). Each question's response has a unique empirically derived weight where lowest possible weight is zero and the highest is 100. The total score and domain score are derived from the relevant items and converted to a score of 0 to 100 with a higher score indicating poorer health status. | Baseline, Day 393 | 
| Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | SGRQ is a health related quality of life questionnaire consisting of 40 items in three domains: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). Each question's response has a unique empirically derived weight where lowest possible weight is zero and the highest is 100. The total score and domain score were derived from the relevant items and converted to a score of 0 to 100 with a higher score indicating poorer health status. Percentage of participants with 4-point, 8-point and 12-point change from baseline in SGRQ-C total score were observed. | Day 393 | 
| Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | The CRQ-SAS is a self-administered questionnaire which consist of 20 items across four domains: dyspnea (5 items), fatigue (4 items), emotional function (7 items), and mastery (4 items). Participants rated their experience on a 7-point scale in response to each item ranging from 1 (maximum impairment) to 7 (no impairment). Individual items were equally weighted, and domain scores were calculated as the mean of all items within each domain; domain score range: 1 (maximum impairment) to 7 (no impairment). | Baseline, Day 393 | 
| Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | The CRQ-SAS is a self-administered questionnaire which consist of 20 items across four domains: dyspnea (5 items), fatigue (4 items), emotional function (7 items), and mastery (4 items). Participants rated their experience on a 7-point scale in response to each item ranging from 1 (maximum impairment) to 7 (no impairment). Individual items were equally weighted, and domain scores were calculated as the mean of all items within each domain; domain score range: 1 (maximum impairment) to 7 (no impairment). Participants with 0.5 point improvement from baseline in the domain scores were observed. | Day 393 | 
| Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Scores at Day 393 | The BODE index is a multi-dimension COPD grading system that incorporates body-mass index (B), degree of airflow obstruction (O), dyspnea (D), and exercise capacity (E) as measured by the modified medical research council (MMRC) dyspnea scale and the 6-minute walk test. The MMRC dyspnea scale is a 5-point scale that measures the level of dyspnea (trouble breathing) experienced by participants where score range is 0 (none) to 4 (very severe ). BODE score is derived into a score range of 0 (healthy) to 10 (severe COPD). | Baseline, Day 393 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Benralizumab, MEDI-563, Pulmonary Disease, Chronic Obstructive