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

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Benralizumab 100 mg
Sponsored by
MedImmune LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive focused on measuring Benralizumab, MEDI-563, Pulmonary Disease, Chronic Obstructive

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Research Site
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Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Benralizumab 100 mg

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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).
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.
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).

Full Information

First Posted
October 21, 2010
Last Updated
August 11, 2016
Sponsor
MedImmune LLC
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT01227278
Brief Title
A Study to Evaluate the Effectiveness of MEDI-563 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
Collaborators
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
Keywords
Benralizumab, MEDI-563, Pulmonary Disease, Chronic Obstructive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
421 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Arm Title
Benralizumab 100 mg
Arm Type
Experimental
Arm Description
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).
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
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).
Intervention Type
Biological
Intervention Name(s)
Benralizumab 100 mg
Other Intervention Name(s)
MEDI-563
Intervention Description
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).
Primary Outcome Measure Information:
Title
Annualized Incidence Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
Description
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.
Time Frame
Day 1 up to 393
Secondary Outcome Measure Information:
Title
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Description
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.
Time Frame
Day 1 up to 561
Title
Number of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
Description
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.
Time Frame
Day 1 up to 393
Title
Percentage of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
Description
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.
Time Frame
Day 1 up to 393
Title
Annual Incidence Rate of Hospitalization Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD)
Description
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.
Time Frame
Day 1 up to 393
Title
Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393
Description
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.
Time Frame
Baseline, Day 393
Title
Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score
Description
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.
Time Frame
Day 393
Title
Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393
Description
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).
Time Frame
Baseline, Day 393
Title
Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393
Description
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.
Time Frame
Day 393
Title
Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Scores at Day 393
Description
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).
Time Frame
Baseline, Day 393

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rene van der Merwe, MBChB
Organizational Affiliation
MedImmune Ltd
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Research Site
City
Marietta
State/Province
Georgia
Country
United States
Facility Name
Research Site
City
Normal
State/Province
Illinois
Country
United States
Facility Name
Research Site
City
Brooklyn
State/Province
New York
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
Country
United States
Facility Name
Research Site
City
Boerne
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Tyler
State/Province
Texas
Country
United States
Facility Name
Research Site
City
Richmond
State/Province
Virginia
Country
United States
Facility Name
Research Site
City
Calgary
State/Province
Alberta
Country
Canada
Facility Name
Research Site
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Research Site
City
Saskatoon
State/Province
Saskatchewan
Country
Canada
Facility Name
Research Site
City
Quebec
Country
Canada
Facility Name
Research Site
City
Hellerup
Country
Denmark
Facility Name
Research Site
City
København NV
Country
Denmark
Facility Name
Research Site
City
Odense C
Country
Denmark
Facility Name
Research Site
City
Århus C
Country
Denmark
Facility Name
Research Site
City
Frankfurt
Country
Germany
Facility Name
Research Site
City
Mainz
Country
Germany
Facility Name
Research Site
City
Gdańsk
Country
Poland
Facility Name
Research Site
City
Kraków
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Łódź
Country
Poland
Facility Name
Research Site
City
Barcelona
Country
Spain
Facility Name
Research Site
City
Lérida
Country
Spain
Facility Name
Research Site
City
Málaga
Country
Spain
Facility Name
Research Site
City
Oviedo
Country
Spain
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research Site
City
Edinburgh
Country
United Kingdom
Facility Name
Research Site
City
Leicester
Country
United Kingdom
Facility Name
Research Site
City
Manchester
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30658649
Citation
Sridhar S, Liu H, Pham TH, Damera G, Newbold P. Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases. Respir Res. 2019 Jan 18;20(1):14. doi: 10.1186/s12931-018-0968-8.
Results Reference
derived
PubMed Identifier
25208464
Citation
Brightling CE, Bleecker ER, Panettieri RA Jr, Bafadhel M, She D, Ward CK, Xu X, Birrell C, van der Merwe R. Benralizumab for chronic obstructive pulmonary disease and sputum eosinophilia: a randomised, double-blind, placebo-controlled, phase 2a study. Lancet Respir Med. 2014 Nov;2(11):891-901. doi: 10.1016/S2213-2600(14)70187-0. Epub 2014 Sep 7.
Results Reference
derived

Learn more about this trial

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

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