Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Benralizumab, MEDI-563, Pulmonary Disease, Chronic Obstructive
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.
Interventions
OTHERPlacebo
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).
BIOLOGICALBenralizumab 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).
Sponsors
AstraZeneca
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Incidence Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | Day 1 up to 393 | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | Day 1 up to 393 | 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) | Day 1 up to 393 | 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) | Day 1 up to 393 | 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 | Baseline, 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. |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Day 1 up to 561 | 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. |
| Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline, 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 | 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 | Baseline, 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). |
| Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | Day 393 | 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. |
Countries
Canada, Denmark, Germany, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 421 participants were screened and 101 participants were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 50 |
| Benralizumab 100 mg Benralizumab (MEDI-563) 100 milligram (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). | 51 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 2 |
| Overall Study | Other | 1 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo | Benralizumab 100 mg | Total |
|---|---|---|---|
| Age, Continuous | 64.6 years STANDARD_DEVIATION 7.5 | 62.9 years STANDARD_DEVIATION 8.2 | 63.7 years STANDARD_DEVIATION 7.9 |
| Sex: Female, Male Female | 21 Participants | 16 Participants | 37 Participants |
| Sex: Female, Male Male | 29 Participants | 35 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 41 / 50 | 44 / 51 |
| serious Total, serious adverse events | 9 / 50 | 14 / 51 |
Outcome results
Primary
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.
Time frame: Day 1 up to 393
Population: The per protocol (PP) population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Annualized Incidence Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 0.92 AECOPD events/person-year |
| Benralizumab 100 mg | Annualized Incidence Rate of Moderate or Severe Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 0.95 AECOPD events/person-year |
p-value: 0.94195% CI: [0.67, 1.58]Van Elteren Test
Secondary
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.
Time frame: Day 1 up to 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Annual Incidence Rate of Hospitalization Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 0.11 hospitalizations/person-year |
| Benralizumab 100 mg | Annual Incidence Rate of Hospitalization Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 0.05 hospitalizations/person-year |
Secondary
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).
Time frame: Baseline, Day 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Scores at Day 393 | Baseline (n=40, 39) | 2.8 units on scale | Standard Deviation 2 |
| Placebo | Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Scores at Day 393 | Change at Day 393 (n=37, 32) | -0.1 units on scale | Standard Deviation 1.4 |
| Benralizumab 100 mg | Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Scores at Day 393 | Baseline (n=40, 39) | 2.9 units on scale | Standard Deviation 1.8 |
| Benralizumab 100 mg | Change From Baseline in Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) Scores at Day 393 | Change at Day 393 (n=37, 32) | -0.5 units on scale | Standard Deviation 1.4 |
Secondary
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).
Time frame: Baseline, Day 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Dyspnea (n=42, 40) | 4.97 units on scale | Standard Deviation 1.45 |
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Dyspnea (n=42, 37) | -0.08 units on scale | Standard Deviation 1.29 |
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Fatigue (n=42, 40) | 4.38 units on scale | Standard Deviation 1.26 |
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Fatigue (n=42, 37) | 0.11 units on scale | Standard Deviation 0.94 |
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Emotional function (n=42, 40) | 4.84 units on scale | Standard Deviation 1.24 |
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Emotional function (n=42, 37) | 0.18 units on scale | Standard Deviation 0.98 |
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Mastery (n=42, 40) | 4.89 units on scale | Standard Deviation 1.5 |
| Placebo | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Mastery (n=42, 37) | 0.24 units on scale | Standard Deviation 1.12 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Mastery (n=42, 37) | 0.28 units on scale | Standard Deviation 1.24 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Dyspnea (n=42, 40) | 4.74 units on scale | Standard Deviation 1.32 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Emotional function (n=42, 40) | 4.72 units on scale | Standard Deviation 1.17 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Dyspnea (n=42, 37) | 0.09 units on scale | Standard Deviation 1 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Mastery (n=42, 40) | 4.67 units on scale | Standard Deviation 1.4 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Baseline: Fatigue (n=42, 40) | 3.96 units on scale | Standard Deviation 1.4 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Emotional function (n=42, 37) | 0.08 units on scale | Standard Deviation 1.18 |
| Benralizumab 100 mg | Change From Baseline in Chronic Respiratory Questionnaire Self-Administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Change at Day 393: Fatigue (n=42, 37) | 0.11 units on scale | Standard Deviation 1.15 |
Secondary
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.
Time frame: Baseline, Day 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Total Score (n=42, 40) | 48.04 units on scale | Standard Deviation 19.14 |
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Total Score (n=42, 37) | -4.43 units on scale | Standard Deviation 11.71 |
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Symptoms (n=42, 40) | 64.59 units on scale | Standard Deviation 24.38 |
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Symptoms (n=42, 37) | -3.19 units on scale | Standard Deviation 17.44 |
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Activity (n=42, 40) | 58.85 units on scale | Standard Deviation 23.22 |
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Activity (n=42, 37) | -5.65 units on scale | Standard Deviation 14.85 |
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Impact (n=42, 40) | 35.94 units on scale | Standard Deviation 18.95 |
| Placebo | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Impact (n=42, 37) | -4.16 units on scale | Standard Deviation 14.62 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Impact (n=42, 37) | -4.95 units on scale | Standard Deviation 16.97 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Total Score (n=42, 40) | 51.75 units on scale | Standard Deviation 20.45 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Activity (n=42, 40) | 61.45 units on scale | Standard Deviation 25.53 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Total Score (n=42, 37) | -5.51 units on scale | Standard Deviation 16.64 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Impact (n=42, 40) | 40.69 units on scale | Standard Deviation 22.49 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Baseline: Symptoms (n=42, 40) | 67.18 units on scale | Standard Deviation 21.47 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Activity (n=42, 37) | -4.37 units on scale | Standard Deviation 24.89 |
| Benralizumab 100 mg | Change From Baseline in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total and Domain Scores at Day 393 | Change at Day 393: Symptoms (n=42, 37) | -9.02 units on scale | Standard Deviation 21.27 |
Secondary
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.
Time frame: Day 1 up to 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 5 participants |
| Benralizumab 100 mg | Number of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 2 participants |
Secondary
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.
Time frame: Day 1 up to 561
Population: The safety population included all participants who received at least one dose of investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 41 participants |
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 9 participants |
| Benralizumab 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 45 participants |
| Benralizumab 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 14 participants |
Secondary
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.
Time frame: Day 1 up to 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 11.9 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants Hospitalized Due to Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) | 5.0 percentage of participants |
Secondary
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.
Time frame: Day 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Dyspnea (n=42, 37) | 28.6 percentage of participants |
| Placebo | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Fatigue (n=42, 37) | 35.7 percentage of participants |
| Placebo | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Emotional function (n=42, 37) | 35.7 percentage of participants |
| Placebo | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Mastery (n=42, 37) | 47.6 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Mastery (n=42, 37) | 37.8 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Dyspnea (n=42, 37) | 32.4 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Emotional function (n=42, 37) | 27.0 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants With a 0.5-Point Improvement in Chronic Respiratory Questionnaire Self-administered Standardized Format (CRQ-SAS) Domain Scores at Day 393 | Day 393: Fatigue (n=42, 37) | 35.1 percentage of participants |
Secondary
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.
Time frame: Day 393
Population: The PP population included all participants who had no major protocol violations, received at least 6 of the 8 total doses of investigational product, and completed the study through Day 393. Here, 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | Day 393, Total: 4-point change (n=42, 37) | 59.5 percentage of participants |
| Placebo | Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | Day 393: 8-point change (n=42, 37) | 38.1 percentage of participants |
| Placebo | Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | Day 393, Total: 12-point change (n=42, 37) | 21.4 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | Day 393, Total: 4-point change (n=42, 37) | 54.1 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | Day 393: 8-point change (n=42, 37) | 40.5 percentage of participants |
| Benralizumab 100 mg | Percentage of Participants With Improvement in COPD-Specific Saint George's Respiratory Questionnaire (SGRQ-C) Total Score | Day 393, Total: 12-point change (n=42, 37) | 24.3 percentage of participants |