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A Study to Evaluate the Onset of Effect and Time Course of Change in Lung Function With Benralizumab in Severe, Uncontrolled Asthma Patients With Eosinophilic Inflammation

Phase 3
Completed
Conditions
Asthma
Interventions
Other: Placebo
Registration Number
NCT02869438
Lead Sponsor
AstraZeneca
Brief Summary

The purpose of this study is to investigate the onset and maintenance of effect of benralizumab on lung function, blood eosinophils, asthma control metrics and quality of life during 12-week treatment in patients with uncontrolled, severe asthma with eosinophilic inflammation. A subset of patients will take part in body plethysmography substudy to further investigate the effect on lung function.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
233
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo armPlaceboPlacebo administered subcutaneously
Benralizumab armBenralizumabBenralizumab administered subcutaneously
Primary Outcome Measures
NameTimeMethod
Change From Baseline (Visit 4) to Day 28 (Visit 8), Day 56 (Visit 9), and Day 84 (Visit 10) in Pre-BD FEV1From first IP dose to Day 84

The average over the mean differences between benralizumab and placebo for change from baseline in pre-BD FEV1 is used to determine if the study is positive and to determine maintenance of effect. The first post baseline time point where the p-value for the mean difference between benralizumab and placebo is less than or equal to 0.05 is used to determine time to onset of effect.

Change From Baseline (Visit 4) to End of Treatment Day 84 (Visit 10) in Residual Volume (RV)From first IP dose to Day 84

Body plethysmography was performed for sub-study patients. Lung volume subdivisions measures were performed by the investigator or qualified designee according to ATS/ERS guidelines.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline to Post Baseline for Pre-BD FVCFrom first IP dose to Day 84

Post baseline visits include Day 3, Day 7, Day 14, Day 28, Day 56, and Day 84.

Change From Baseline to End of Treatment in FeNOFrom first IP dose to Day 84

Airway inflammation was evaluated via fractional exhaled nitric oxide (FeNO) measurement.

Change From Baseline to End of Treatment in Ratio of Residual Volume (RV) and Total Lung Capacity (TLC) for Sub-study PatientsFrom first IP dose to Day 84

Lung volume subdivisions include total lung capacity (TLC), residual volume (RV), vital capacity (VC), functional residual capacity (FRC), and inspiratory capacity (IC), as well as airway resistance (Raw and SGaw) measurements.

Change From Baseline to End of Treatment in Inspiratory Capacity (IC) for Sub-study PatientsFrom first IP dose to Day 84

Lung volume subdivisions include total lung capacity (TLC), residual volume (RV), vital capacity (VC), functional residual capacity (FRC), and inspiratory capacity (IC), as well as airway resistance (Raw and SGaw) measurements.

Change From Baseline to End of Treatment in Functional Residual Capacity (FRC) for Sub-study PatientsFrom first IP dose to Day 84

Lung volume subdivisions include total lung capacity (TLC), residual volume (RV), vital capacity (VC), functional residual capacity (FRC), and inspiratory capacity (IC), as well as airway resistance (Raw and SGaw) measurements.

Change From Baseline to End of Treatment in Vital Capacity (VC) for Sub-study PatientsFrom first IP dose to Day 84

Lung volume subdivisions include total lung capacity (TLC), residual volume (RV), vital capacity (VC), functional residual capacity (FRC), and inspiratory capacity (IC), as well as airway resistance (Raw and SGaw) measurements.

Duration of IP AdministrationFrom first IP to last IP

Duration of IP administration is last IP dose date - first IP dose +1.

Percentage of Pre-BD FEV1 ResponderFrom first IP dose to Day 84

Pre-BD FEV1 responder is defined as change from baseline in FEV1 \>=100 ml

Percent Change From Baseline to End of Treatment in Eosinophils CountsFrom first IP dose to Day 84

Percent change from baseline to Day 84

Change From Baseline (Visit 4) to Post Baseline Visits in Pre-BD FEV1From first IP dose to Day 84

Post baseline visits include Day 3, Day 7, Day 14, Day 28, Day 56, Day 84. \[Note: Day 28, 56, 84 are presented in the Primary measure.\]

Change From Baseline in St. George's Respiratory Questionnaire (SGRQ)From first IP dose to Day 84

The SGRQ is designed to measure health impairment in patients with asthma and COPD. It contains two parts: Part 1 (Questions 1 to 8) covers the patients' recollection of their symptoms over a preceding 4 weeks; Part 2, 42 items, relates to the daily activity and psychosocial impacts of the individual's respiratory condition. Total score is presented as a percentage of overall impairment, in which 100 represents the worst possible health status, while 0 indicates the best.

Change From Baseline to End of Treatment in Total Lung Capacity (TLC) for Sub-study PatientsFrom first IP dose to Day 84

Lung volume subdivisions include total lung capacity (TLC), residual volume (RV), vital capacity (VC), functional residual capacity (FRC), and inspiratory capacity (IC), as well as airway resistance (Raw and SGaw) measurements.

Change From Baseline in ACQ-6From first IP dose to Day 84

ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of \<=0.75 indicates well-controlled asthma, scores between 0.75 to \<=1.5 indicate partly controlled asthma, and \>1.5 indicates not well controlled asthma.

Trial Locations

Locations (1)

Research Site

🇵🇭

Quezon City, Philippines

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