Trial Outcomes & Findings for 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 (NCT NCT02869438)

NCT ID: NCT02869438

Last Updated: 2019-10-29

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 233 participants
• Primary outcome timeframe: From first IP dose to Day 84
• Results posted on: 2019-10-29

Participant Flow

233 participants were randomized to receive treatment in study D3250C00038 (Solana) with benralizumab 30 mg or placebo. Of the 233 patients randomised, all (100.0%) received treatment with study drug. 118 (50.6%) patients received benralizumab 30 mg and 115 (49.4%) patients received placebo.

Participant milestones

Measure	Benra 30 mg 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Overall Study STARTED	118	115
Overall Study COMPLETED	115	113
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Measure	Benra 30 mg 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Overall Study Lost to Follow-up	1	0
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Total n=233 Participants Total of all reporting groups
Age, Continuous	51.9 years STANDARD_DEVIATION 13.62 • n=5 Participants	50.9 years STANDARD_DEVIATION 12.34 • n=7 Participants	51.4 years STANDARD_DEVIATION 12.99 • n=5 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	83 Participants n=7 Participants	157 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	32 Participants n=7 Participants	76 Participants n=5 Participants
Race/Ethnicity, Customized White	69 Participants n=5 Participants	67 Participants n=7 Participants	136 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Asian	39 Participants n=5 Participants	40 Participants n=7 Participants	79 Participants n=5 Participants
Race/Ethnicity, Customized Other	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

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.

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline (Visit 4) to Day 28 (Visit 8), Day 56 (Visit 9), and Day 84 (Visit 10) in Pre-BD FEV1 Day 28	0.21 Liter Standard Deviation 0.335	0.132 Liter Standard Deviation 0.316
Change From Baseline (Visit 4) to Day 28 (Visit 8), Day 56 (Visit 9), and Day 84 (Visit 10) in Pre-BD FEV1 Day 56	0.22 Liter Standard Deviation 0.367	0.203 Liter Standard Deviation 0.349
Change From Baseline (Visit 4) to Day 28 (Visit 8), Day 56 (Visit 9), and Day 84 (Visit 10) in Pre-BD FEV1 Day 84	0.209 Liter Standard Deviation 0.344	0.149 Liter Standard Deviation 0.366

PRIMARY outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline (Visit 4) to End of Treatment Day 84 (Visit 10) in Residual Volume (RV)	-0.415 Liter Standard Deviation 0.609	-0.208 Liter Standard Deviation 0.528

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

Percent change from baseline to Day 84

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Percent Change From Baseline to End of Treatment in Eosinophils Counts	-88.55 Percent change Interval -100.0 to -12.5	11.55 Percent change Interval -91.4 to 833.3

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

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.]

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline (Visit 4) to Post Baseline Visits in Pre-BD FEV1 Day 3	0.104 Liter Standard Deviation 0.223	0.081 Liter Standard Deviation 0.269
Change From Baseline (Visit 4) to Post Baseline Visits in Pre-BD FEV1 Day 7	0.125 Liter Standard Deviation 0.229	0.081 Liter Standard Deviation 0.263
Change From Baseline (Visit 4) to Post Baseline Visits in Pre-BD FEV1 Day 14	0.126 Liter Standard Deviation 0.3	0.1 Liter Standard Deviation 0.287

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

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

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to Post Baseline for Pre-BD FVC Day 3	0.122 Liter Standard Deviation 0.247	0.11 Liter Standard Deviation 0.267
Change From Baseline to Post Baseline for Pre-BD FVC Day 7	0.138 Liter Standard Deviation 0.277	0.099 Liter Standard Deviation 0.292
Change From Baseline to Post Baseline for Pre-BD FVC Day 14	0.126 Liter Standard Deviation 0.331	0.111 Liter Standard Deviation 0.312
Change From Baseline to Post Baseline for Pre-BD FVC Day 28	0.21 Liter Standard Deviation 0.347	0.134 Liter Standard Deviation 0.34
Change From Baseline to Post Baseline for Pre-BD FVC Day 56	0.211 Liter Standard Deviation 0.404	0.187 Liter Standard Deviation 0.369
Change From Baseline to Post Baseline for Pre-BD FVC Day 84	0.213 Liter Standard Deviation 0.376	0.131 Liter Standard Deviation 0.359

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

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

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Percentage of Pre-BD FEV1 Responder Day 3	48.2 Percentage of Participants	37.4 Percentage of Participants
Percentage of Pre-BD FEV1 Responder Day 7	48.3 Percentage of Participants	42.0 Percentage of Participants
Percentage of Pre-BD FEV1 Responder Day 14	50.0 Percentage of Participants	38.9 Percentage of Participants
Percentage of Pre-BD FEV1 Responder Day 28	57.6 Percentage of Participants	46.9 Percentage of Participants
Percentage of Pre-BD FEV1 Responder Day 56	62.1 Percentage of Participants	55.8 Percentage of Participants
Percentage of Pre-BD FEV1 Responder Day 84	57.9 Percentage of Participants	51.8 Percentage of Participants

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

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.

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline in ACQ-6 Day 14	-0.989 Score on a scale Standard Deviation 0.901	-0.665 Score on a scale Standard Deviation 0.837
Change From Baseline in ACQ-6 Day 28	-1.126 Score on a scale Standard Deviation 0.947	-0.693 Score on a scale Standard Deviation 0.869
Change From Baseline in ACQ-6 Day 56	-1.164 Score on a scale Standard Deviation 1.132	-0.827 Score on a scale Standard Deviation 1.023
Change From Baseline in ACQ-6 Day 84	-1.355 Score on a scale Standard Deviation 1.146	-0.867 Score on a scale Standard Deviation 1.114

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

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.

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Day 28	-16.956 Score on a scale Standard Deviation 15.51	-9.444 Score on a scale Standard Deviation 14.136
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Day 56	-19.941 Score on a scale Standard Deviation 21.528	-13.802 Score on a scale Standard Deviation 16.705
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Day 84	-23.343 Score on a scale Standard Deviation 20.302	-14.385 Score on a scale Standard Deviation 18.836

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

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

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in FeNO	5.92 ppb Standard Deviation 45.295	0.05 ppb Standard Deviation 27.634

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in Total Lung Capacity (TLC) for Sub-study Patients	-0.276 Liter Standard Deviation 0.677	-0.175 Liter Standard Deviation 0.418

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in Ratio of Residual Volume (RV) and Total Lung Capacity (TLC) for Sub-study Patients	-0.05 ratio Standard Deviation 0.056	-0.026 ratio Standard Deviation 0.087

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in Inspiratory Capacity (IC) for Sub-study Patients	0.119 Liter Standard Deviation 0.447	-0.268 Liter Standard Deviation 0.603

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in Functional Residual Capacity (FRC) for Sub-study Patients	-0.394 Liter Standard Deviation 0.783	0.093 Liter Standard Deviation 0.466

SECONDARY outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in Vital Capacity (VC) for Sub-study Patients	0.139 Liter Standard Deviation 0.245	0.033 Liter Standard Deviation 0.676

SECONDARY outcome

Timeframe: From first IP to last IP

Population: Safety analysis set

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

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Duration of IP Administration	55.9 Days Standard Deviation 7.83	56.2 Days Standard Deviation 7.61

OTHER_PRE_SPECIFIED outcome

Timeframe: From first dose to end of treatment period (Day 84)

Population: PK analysis set

PK sample was collected pre-dose at each visit

Outcome measures

Measure	Benra 30 mg n=117 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Serum Concentration of Benralizumab Baseline	1.95 ng/mL Geometric Coefficient of Variation NA Only 1 patient had PK concentration detectable, ie, PK concentration \<LLOQ for 115 participants.	—
Serum Concentration of Benralizumab Day 3	1266.78 ng/mL Geometric Coefficient of Variation 199.59	—
Serum Concentration of Benralizumab Day 7	1449.47 ng/mL Geometric Coefficient of Variation 125.02	—
Serum Concentration of Benralizumab Day 14	1317.92 ng/mL Geometric Coefficient of Variation 79.53	—
Serum Concentration of Benralizumab Day 28	738.47 ng/mL Geometric Coefficient of Variation 80.77	—
Serum Concentration of Benralizumab Day 56	1015.72 ng/mL Geometric Coefficient of Variation 59.74	—
Serum Concentration of Benralizumab Day 84	1079.22 ng/mL Geometric Coefficient of Variation 73.24	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First IP dose cycle (ie, data collected on Days 3, 7, 14 and 28)

Population: PK analysis set

PK parameters are derived in patients with at least three qualifiable serum PK concentrations post first dose (collected on Day 3, 7, and either 14, or 28)

Outcome measures

Measure	Benra 30 mg n=117 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
PK Parameter of Benralizumab (Cmax)	1729.6 ng/mL Geometric Coefficient of Variation 36.8	—

OTHER_PRE_SPECIFIED outcome

Timeframe: From first IP dose to end of treatment period (Day 84)

Population: Safety analysis set

Anti-drug antibody responses at baseline and post baseline, including nAb responses

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Anti-drug Antibody Responses ADA prevalence	7 Participants	2 Participants
Anti-drug Antibody Responses nAb prevalence	2 Participants	0 Participants
Anti-drug Antibody Responses Both baseline and post baseline positive	1 Participants	2 Participants
Anti-drug Antibody Responses Only post baseline positive	5 Participants	0 Participants
Anti-drug Antibody Responses Only baseline positive	1 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

The patient global impression of severity (PGI-S) is a single item designed to capture the patient's perception of overall symptom severity at the time of the completion using a 6-point categorical response scale (no symptom [0] to very severe symptom [5])

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in PGI-S	-1.2 Score on a scale Standard Deviation 1.31	-0.8 Score on a scale Standard Deviation 1.21

OTHER_PRE_SPECIFIED outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

Clinician global impression of change (CGI-C) is used for an overall evaluation of response to treatment. The investigator is asked to rate the degree of change in overall asthma status compare to the start of treatment. A 7-point rating scale is used from 1=very much improved to 7=very much worse.

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in CGI-C Very much improved	18 Participants	10 Participants
Change From Baseline to End of Treatment in CGI-C Much improved	39 Participants	36 Participants
Change From Baseline to End of Treatment in CGI-C Minimally improved	39 Participants	28 Participants
Change From Baseline to End of Treatment in CGI-C No change	17 Participants	28 Participants
Change From Baseline to End of Treatment in CGI-C Minimally worse	0 Participants	7 Participants
Change From Baseline to End of Treatment in CGI-C Much worse	0 Participants	1 Participants
Change From Baseline to End of Treatment in CGI-C Very much worse	0 Participants	0 Participants
Change From Baseline to End of Treatment in CGI-C Missing	5 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From first IP dose to Day 84

Population: Full analysis set

Patient global impression of change (PGI-C) is used for an overall evaluation of response to treatment. The patient is asked to rate the degree of change in overall asthma status compare to the start of treatment. A 7-point rating scale is used from 1=very much improved to 7=very much worse.

Outcome measures

Measure	Benra 30 mg n=118 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in PGI-C Very much improved	32 Participants	17 Participants
Change From Baseline to End of Treatment in PGI-C Much improved	42 Participants	35 Participants
Change From Baseline to End of Treatment in PGI-C Minimally improved	23 Participants	29 Participants
Change From Baseline to End of Treatment in PGI-C No change	14 Participants	27 Participants
Change From Baseline to End of Treatment in PGI-C Minimally worse	1 Participants	4 Participants
Change From Baseline to End of Treatment in PGI-C Much worse	1 Participants	1 Participants
Change From Baseline to End of Treatment in PGI-C Very much worse	1 Participants	0 Participants
Change From Baseline to End of Treatment in PGI-C Missing	4 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in Specific Airway Resistance (SGaw) for Sub-study Patients	-0.05 1/(kPa*sec) Standard Deviation 0.146	0.052 1/(kPa*sec) Standard Deviation 0.224

OTHER_PRE_SPECIFIED outcome

Timeframe: From first IP dose to Day 84

Population: Body plethysmography sub-study analysis set

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.

Outcome measures

Measure	Benra 30 mg n=18 Participants 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=22 Participants 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Change From Baseline to End of Treatment in Airway Resistance (Raw) for Sub-study Patients	-0.233 kPa/L/sec Standard Deviation 1.509	-0.2 kPa/L/sec Standard Deviation 0.532

Adverse Events

Benra 30 mg

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Measure	Benra 30 mg n=118 participants at risk 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 participants at risk 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Cardiac disorders Coronary artery disease	0.00% 0/118 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	0.87% 1/115 • Number of events 1 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Immune system disorders Drug hypersensitivity	0.85% 1/118 • Number of events 1 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	0.00% 0/115 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Infections and infestations Lower respiratory tract infection	0.00% 0/118 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	0.87% 1/115 • Number of events 1 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Infections and infestations Pneumonia	0.00% 0/118 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	1.7% 2/115 • Number of events 2 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/118 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	0.87% 1/115 • Number of events 1 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Nervous system disorders Migraine	0.00% 0/118 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	0.87% 1/115 • Number of events 1 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/118 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	1.7% 2/115 • Number of events 2 • From informed consent form was signed to end of study (ie, Day 112 follow-up)

Other adverse events

Measure	Benra 30 mg n=118 participants at risk 12-week treatment period and receive Benra 30 mg at Day 0, Day 28 (±3 days), and Day 56 (±3 days).	Placebo n=115 participants at risk 12-week treatment period and receive Placebo at Day 0, Day 28 (±3 days), and Day 56 (±3 days).
Infections and infestations Bronchitis	5.1% 6/118 • Number of events 6 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	2.6% 3/115 • Number of events 3 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Infections and infestations Nasopharyngitis	6.8% 8/118 • Number of events 9 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	5.2% 6/115 • Number of events 7 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Infections and infestations Upper respiratory tract infection	5.1% 6/118 • Number of events 7 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	5.2% 6/115 • Number of events 8 • From informed consent form was signed to end of study (ie, Day 112 follow-up)
Respiratory, thoracic and mediastinal disorders Asthma	9.3% 11/118 • Number of events 11 • From informed consent form was signed to end of study (ie, Day 112 follow-up)	15.7% 18/115 • Number of events 22 • From informed consent form was signed to end of study (ie, Day 112 follow-up)

Additional Information

Ubaldo Martin, Global Clinical Lead Benralizumab

AstraZeneca

Phone: +1 301 398 0163

Email: Ubaldo.Martin@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee ≥ 60 days prior to submission of material for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ's Confidential Information without AZ's written approval. AZ can request Inst. and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication or presentation.
• Publication restrictions are in place

Restriction type: OTHER