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

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01227278
First received: October 21, 2010
Last updated: August 11, 2016
Last verified: March 2015

October 21, 2010
August 11, 2016
November 2010
January 2013   (final data collection date for primary outcome measure)
Annualized Incidence Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) [ Time Frame: Day 1 up to 393 ] [ Designated as safety issue: No ]
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.
To evaluate multiple SC doses of MEDI 563 on the rate of moderate-to-severe acute exacerbations in COPD (AECOPD) in adult subjects. [ Time Frame: Study Day 393 ] [ Designated as safety issue: Yes ]
Testing the differences in number of moderate-to-severe AECOPDs between the MEDI-563 treatment group and the placebo group.
Complete list of historical versions of study NCT01227278 on ClinicalTrials.gov Archive Site
  • Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 up to 561 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Day 1 up to 393 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 up to 393 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 1 up to 393 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 393 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 393 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 393 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 393 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline, Day 393 ] [ Designated as safety issue: No ]
    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).
Adverse Events and Severe Adverse Events will be categorically summarized by organ class and relationship to investigational product. [ Time Frame: Study Day 561 ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Study to Evaluate the Effectiveness of MEDI-563 in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
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
To evaluate the effect of the drug in moderate to severe Chronic Obstructive Pulmonary Disease (COPD) in Adults.
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.
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Pulmonary Disease, Chronic Obstructive
  • Other: Placebo
    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).
  • Biological: Benralizumab 100 mg
    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).
    Other Name: MEDI-563
  • Placebo Comparator: Placebo
    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: Other: Placebo
  • Experimental: Benralizumab 100 mg
    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: Biological: Benralizumab 100 mg
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
421
July 2013
January 2013   (final data collection date for primary outcome measure)

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.
Both
40 Years to 85 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Denmark,   Germany,   Poland,   Spain,   United Kingdom
 
NCT01227278
MI-CP196, 2010-020127-52
No
Not Provided
Not Provided
MedImmune LLC
MedImmune LLC
AstraZeneca
Study Director: Rene van der Merwe, MBChB MedImmune Ltd
MedImmune LLC
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP