Severe Uncontrolled Asthma
Conditions
Keywords
Pediatric, PK, severe asthma
Brief summary
This study will evaluate the PK, PD and long-term safety of Benralizumab administered subcutaneously in 30 children aged 6 to 11 years with severe eosinophilic asthma. Up to an additional 3 Japanese patients aged 12 to 14 years will be enrolled to meet local regulatory requirements.
Interventions
DRUGBenralizumab
Dose will be stratified by body weight at screening: Patients will receive Dose 1 or Dose 2 of Benralizumab administered by SC injection at Day 0 and Weeks 4, 8, and 16, 24, 32, and 40.
Sponsors
Iqvia Pty Ltd
Parexel
Covance
PPD Development, LP
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
Patients are eligible to be included in the study only if all of the following inclusion criteria and none of the
Exclusion criteria
apply: 1. Parent(s)/guardian are able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. If applicable, the participant must be able and willing to give assent to take part in the study according to the local requirement. 2. Patient must be 6 to 11 years of age inclusive (6 to 14 years of age inclusive in Japan), at the time of signing the ICF. 3. Diagnosis of severe asthma, defined by the regional guidelines for at least 12 months prior to Visit 1. 4. A previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids and/or hospitalization in the 12 months prior to Visit 1. 5. Peripheral blood eosinophil count of ≥ 150 cells / µL at Visit 1. 6. A well-documented requirement for regular treatment with ICS: eg. total daily dose equivalent to ≥ 250 µg fluticasone propionate, in the 12 months prior to Visit 1, with or without maintenance oral corticosteroids. 7. Current treatment with at least 1 additional controller medication, such as inhaled LABA, leukotriene receptor antagonist, long acting anti-muscarinic agent, or theophylline, since at least 3 months prior to Visit 1. 8. Pre-bronchodilator FEV1 ≤ 110% predicted normal, or, FEV1/Forced Vital Capacity (FVC) ratio ≤ 0.8. 9. Body weight ≥15 kg. 10. Male or female 11. Females of childbearing potential (FOCBP) who are sexually active, as judged by the investigator, must commit to consistent and correct use of an acceptable method of contraception for the duration of the study and for 4 months after the last dose of IP.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Baseline (Day 0) and at Weeks 4, 8, 12, 16, 24 and 48 | Blood samples were collected for determination of eosinophil count levels and were assessed in a central laboratory. Baseline is the last non-missing measurement prior to the first dose of study treatment. |
| Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab | Pre-dose on Days 0, 28 and post-dose on Days 1, 7, 14 | Blood samples were collected to determine the AUC0-28 of benralizumab and it was calculated by linear up/log down trapezoidal summation. The PK parameters were estimated using non-compartmental analysis method. |
| Maximum Observed Serum Concentration (Cmax) of Benralizumab | Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit | Blood samples were collected to determine Cmax of benralizumab and it was directly calculated from the individual concentration-time curve. The PK parameters were estimated using non-compartmental analysis method. |
| Terminal Phase Elimination Half-Life (t1/2) of Benralizumab | Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit | Blood samples were collected to determine the t1/2 of benralizumab and it was calculated as natural logarithm of 2 \[ln(2)\]/terminal rate constant (λZ). This was an EBE derived posthoc using population PK analysis. |
| Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab | Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit | Blood samples were collected to determine the tmax of benralizumab and it was directly calculated from the individual concentration-time curve. The PK parameters were estimated using non-compartmental analysis method. |
| Trough Concentration of Benralizumab at Week 16 (Ctrough16) | Pre-dose on Day 112 | Blood samples were collected to determine the trough concentration at Week 16, the lowest concentration reached by benralizumab before the next dose was administered. The PK parameters were estimated using non-compartmental analysis method. |
| Clearance of Benralizumab | Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit | Blood samples were collected to determine the clearance of benralizumab. This was an empirical Bayesian estimate (EBE) derived posthoc using population PK analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight-Adjusted Clearance of Benralizumab | Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit | Blood samples were collected to determine the clearance of benralizumab. This was an EBE derived posthoc using population PK analysis. |
| Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Pre-dose at Baseline (Day 0), Weeks 8, 16 and 24 and post-dose at Week 48; and at early discontinuation or withdrawal visit | Blood samples were analyzed for the presence of ADAs for benralizumab. ADA prevalence: ADA positive (+ve) at any time point including baseline and/or post baseline. Treatment induced ADA+ve: ADA negative (-ve) at baseline and post-baseline ADA+ve. Treatment-boosted ADA+ve: baseline +ve ADA titer that was boosted by \>4-fold or higher-level following study drug administration. Treatment-emergent ADA+ve: either treatment-induced ADA+ve or treatment-boosted ADA+ve. Persistently +ve ADA: having at least 2 post-baseline ADA+ve assessments with at least 16 weeks (112 days) between the first and last +ve assessments, or an ADA+ve result at the last available assessment. Transiently +ve ADA: having at least 1 post-baseline ADA+ve assessment(s) and not persistently ADA+ve. Neutralizing antibodies (nAb) prevalence: nAb+ve at baseline and/or post-baseline. Treatment-induced nAb+ve (nAb incidence): nAb-ve at baseline (or ADA-ve at baseline) and nAb+ve at any post-baseline visit. |
| Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Baseline (Day 0), at Weeks 16 and 48; and at early discontinuation or withdrawal visit | The ACQ-IA is a 6-item assessment comprised of 6 patient-reported items. Participants were asked to record their experience with 5 symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheezing) and use of short-acting beta-2 agonist (SABA) over the previous week using a 7-point scale (0 = no impairment; and 6 = maximum impairment). The ACQ-IA score was calculated by the mean of the 7 equally weighted items. The score ranged from 0 (well controlled) to 6 (extremely poorly controlled). Higher scores indicated poor asthma control. Baseline is the last non-missing measurement prior to the first dose of study treatment. |
| Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | At Weeks 16 and 48; and at early discontinuation or withdrawal visit | The PGIC-IA and CGIC instruments were used for an overall evaluation of response to treatment, conducted separately by the Investigator and by the participant (administered by trained individuals to help the child understand the question and response options), using a 7-point scale: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. The Investigator (clinician) and the participant were asked to rate the degree of change in the overall asthma status compared to the start of study treatment visit. Participants were defined as responders based on categorized responses for PGIC-IA and CGIC. Responder status categories included Improved=Very much improved, Much improved, Minimally improved, Much improved=Much improved, Very much improved, Very much improved=Very much improved. CGIC = PGIC-IA indicates agreement between CGIC and PGIC-IA assessments of response to treatment at the same visit. |
| Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Baseline (Day 0) and at Weeks 16 and 48 | The FEV1 was defined as the volume of air exhaled from the lungs in the first second of a forced expiration and was measured by spirometry. Baseline is the last non-missing measurement with acceptable quality prior to the first dose of study treatment. |
Countries
Japan, United States
Participant flow
Recruitment details
This Phase III, open-label, parallel group study was conducted in pediatric participants with severe eosinophilic asthma at 17 investigational sites in the United States and Japan between 21 Nov 2019 and 12 Sep 2022.
Pre-assignment details
The study consisted of a screening period (up to 4 weeks), treatment period \[2 parts; Part A (16 weeks) followed by Part B (32 weeks)\], and a safety follow-up visit at Week 52.A total of 30 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Benralizumab Dose 1, Aged 6-14 Years All participants with body weight \<35 kg at screening received benralizumab Dose 1 SC injection once daily on Day 0 and at Weeks 4, 8, and 16 in Part A, followed by benralizumab Dose 1 at Weeks 24, 32, and 40 in Part B. | 15 |
| Benralizumab Dose 2, Aged 6-14 Years All participants with body weight \>=35 kg or aged 12-14 years (irrespective of body weight) at screening received benralizumab Dose 2 SC injection once daily on Day 0 and at Weeks 4, 8, and 16 in Part A, followed by benralizumab Dose 2 at Weeks 24, 32, and 40 in Part B. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by parent/guardian | 0 | 1 |
Baseline characteristics
| Characteristic | Benralizumab Dose 1, Aged 6-14 Years | Benralizumab Dose 2, Aged 6-14 Years | Total |
|---|---|---|---|
| Age, Continuous | 8.3 years STANDARD_DEVIATION 2.02 | 9.8 years STANDARD_DEVIATION 1.93 | 9.0 years STANDARD_DEVIATION 2.09 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 8 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 5 Participants | 8 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 14 Participants | 10 Participants | 24 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 11 Participants | 8 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 13 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 13 / 15 | 9 / 13 | 13 / 15 | 11 / 15 |
| serious Total, serious adverse events | 1 / 15 | 2 / 13 | 1 / 15 | 4 / 15 |
Outcome results
Primary
Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab
Blood samples were collected to determine the AUC0-28 of benralizumab and it was calculated by linear up/log down trapezoidal summation. The PK parameters were estimated using non-compartmental analysis method.
Time frame: Pre-dose on Days 0, 28 and post-dose on Days 1, 7, 14
Population: The Non-compartmental analysis (NCA) set consisted of all participants who received the first dose of benralizumab for whom PK blood samples were not assumed to be affected by factors such as protocol violations and who had at least 3 quantifiable serum PK observations post first dose on Days 1, 7, 14, and 28. Only those participants with data available were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab | 36918.01 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 24.61 |
| Benralizumab Dose 2, Aged 6-11 Years | Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab | 75593.37 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 39.96 |
| Benralizumab Dose 1, Aged 6-14 Years | Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab | 36918.01 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 24.61 |
| Benralizumab Dose 2, Aged 6-14 Years | Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab | 73670.51 nanogram*day per milliliter (ng*day/mL) | Geometric Coefficient of Variation 38.86 |
Primary
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48
Blood samples were collected for determination of eosinophil count levels and were assessed in a central laboratory. Baseline is the last non-missing measurement prior to the first dose of study treatment.
Time frame: Baseline (Day 0) and at Weeks 4, 8, 12, 16, 24 and 48
Population: The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 16 | -446.7 cells/microliters | Standard Deviation 279.12 |
| All Participants | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 24 | -354.2 cells/microliters | Standard Deviation 323.99 |
| All Participants | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 8 | -445.3 cells/microliters | Standard Deviation 276.2 |
| All Participants | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 4 | -447.3 cells/microliters | Standard Deviation 283.76 |
| All Participants | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 48 | -434.0 cells/microliters | Standard Deviation 286.15 |
| All Participants | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 12 | -443.3 cells/microliters | Standard Deviation 286.85 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 12 | -455.8 cells/microliters | Standard Deviation 419.32 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 24 | -436.9 cells/microliters | Standard Deviation 405.9 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 4 | -436.9 cells/microliters | Standard Deviation 408.28 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 8 | -453.8 cells/microliters | Standard Deviation 396.03 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 16 | -402.7 cells/microliters | Standard Deviation 384.61 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 48 | -453.8 cells/microliters | Standard Deviation 392.78 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 12 | -443.3 cells/microliters | Standard Deviation 286.85 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 4 | -447.3 cells/microliters | Standard Deviation 283.76 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 8 | -445.3 cells/microliters | Standard Deviation 276.2 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 16 | -446.7 cells/microliters | Standard Deviation 279.12 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 24 | -354.2 cells/microliters | Standard Deviation 323.99 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 48 | -434.0 cells/microliters | Standard Deviation 286.15 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 48 | -474.3 cells/microliters | Standard Deviation 385.04 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 24 | -457.9 cells/microliters | Standard Deviation 397.77 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 8 | -470.7 cells/microliters | Standard Deviation 374.25 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 4 | -455.3 cells/microliters | Standard Deviation 385.58 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 16 | -430.0 cells/microliters | Standard Deviation 378.68 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 | Week 12 | -472.9 cells/microliters | Standard Deviation 393.49 |
Primary
Clearance of Benralizumab
Blood samples were collected to determine the clearance of benralizumab. This was an empirical Bayesian estimate (EBE) derived posthoc using population PK analysis.
Time frame: Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit
Population: The PK analysis set consisted of all participants who received at least 1 dose of benralizumab for whom PK blood samples were not assumed to be affected by factors such as protocol violations and who had at least 1 post dose quantifiable serum PK observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Clearance of Benralizumab | 0.156 liter (L) per day | Standard Deviation 0.0598 |
Primary
Maximum Observed Serum Concentration (Cmax) of Benralizumab
Blood samples were collected to determine Cmax of benralizumab and it was directly calculated from the individual concentration-time curve. The PK parameters were estimated using non-compartmental analysis method.
Time frame: Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit
Population: The NCA set consisted of all participants who received the first dose of benralizumab for whom PK blood samples were not assumed to be affected by factors such as protocol violations and who had at least 3 quantifiable serum PK observations post first dose on Days 1, 7, 14, and 28.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Maximum Observed Serum Concentration (Cmax) of Benralizumab | 1901.18 ng/mL | Geometric Coefficient of Variation 28.42 |
| Benralizumab Dose 2, Aged 6-11 Years | Maximum Observed Serum Concentration (Cmax) of Benralizumab | 3118.69 ng/mL | Geometric Coefficient of Variation 47.35 |
| Benralizumab Dose 1, Aged 6-14 Years | Maximum Observed Serum Concentration (Cmax) of Benralizumab | 1901.18 ng/mL | Geometric Coefficient of Variation 28.42 |
| Benralizumab Dose 2, Aged 6-14 Years | Maximum Observed Serum Concentration (Cmax) of Benralizumab | 3090.85 ng/mL | Geometric Coefficient of Variation 43.66 |
Primary
Terminal Phase Elimination Half-Life (t1/2) of Benralizumab
Blood samples were collected to determine the t1/2 of benralizumab and it was calculated as natural logarithm of 2 \[ln(2)\]/terminal rate constant (λZ). This was an EBE derived posthoc using population PK analysis.
Time frame: Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit
Population: The PK analysis set consisted of all participants who received at least 1 dose of benralizumab for whom PK blood samples were not assumed to be affected by factors such as protocol violations and who had at least 1 post dose quantifiable serum PK observation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Terminal Phase Elimination Half-Life (t1/2) of Benralizumab | 14.4 day |
Primary
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab
Blood samples were collected to determine the tmax of benralizumab and it was directly calculated from the individual concentration-time curve. The PK parameters were estimated using non-compartmental analysis method.
Time frame: Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit
Population: The NCA set consisted of all participants who received the first dose of benralizumab for whom PK blood samples were not assumed to be affected by factors such as protocol violations and who had at least 3 quantifiable serum PK observations post first dose on Days 1, 7, 14, and 28.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Participants | Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab | 6.91 day |
| Benralizumab Dose 2, Aged 6-11 Years | Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab | 7.26 day |
| Benralizumab Dose 1, Aged 6-14 Years | Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab | 6.91 day |
| Benralizumab Dose 2, Aged 6-14 Years | Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab | 7.94 day |
Primary
Trough Concentration of Benralizumab at Week 16 (Ctrough16)
Blood samples were collected to determine the trough concentration at Week 16, the lowest concentration reached by benralizumab before the next dose was administered. The PK parameters were estimated using non-compartmental analysis method.
Time frame: Pre-dose on Day 112
Population: The NCA set consisted of all participants who received the first dose of benralizumab for whom PK blood samples were not assumed to be affected by factors such as protocol violations and who had at least 3 quantifiable serum PK observations post first dose on Days 1, 7, 14, and 28. Only those participants with data available were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Trough Concentration of Benralizumab at Week 16 (Ctrough16) | 142.42 ng/mL | Geometric Coefficient of Variation 256.34 |
| Benralizumab Dose 2, Aged 6-11 Years | Trough Concentration of Benralizumab at Week 16 (Ctrough16) | 339.35 ng/mL | Geometric Coefficient of Variation 409.24 |
| Benralizumab Dose 1, Aged 6-14 Years | Trough Concentration of Benralizumab at Week 16 (Ctrough16) | 142.42 ng/mL | Geometric Coefficient of Variation 256.34 |
| Benralizumab Dose 2, Aged 6-14 Years | Trough Concentration of Benralizumab at Week 16 (Ctrough16) | 340.46 ng/mL | Geometric Coefficient of Variation 363.69 |
Secondary
Body Weight-Adjusted Clearance of Benralizumab
Blood samples were collected to determine the clearance of benralizumab. This was an EBE derived posthoc using population PK analysis.
Time frame: Pre-dose on Days 0, 28, 56, 112, 168 and post-dose on Days 1, 7, 14, 84, 336; and at early discontinuation or withdrawal visit
Population: The PK analysis set consisted of all participants who received at least 1 dose of benralizumab for whom PK blood samples were not assumed to be affected by factors such as protocol violations and who had at least 1 post dose quantifiable serum PK observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Body Weight-Adjusted Clearance of Benralizumab | 0.00408 L/day/kilogram | Standard Deviation 0.000764 |
Secondary
Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48
The ACQ-IA is a 6-item assessment comprised of 6 patient-reported items. Participants were asked to record their experience with 5 symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, and wheezing) and use of short-acting beta-2 agonist (SABA) over the previous week using a 7-point scale (0 = no impairment; and 6 = maximum impairment). The ACQ-IA score was calculated by the mean of the 7 equally weighted items. The score ranged from 0 (well controlled) to 6 (extremely poorly controlled). Higher scores indicated poor asthma control. Baseline is the last non-missing measurement prior to the first dose of study treatment.
Time frame: Baseline (Day 0), at Weeks 16 and 48; and at early discontinuation or withdrawal visit
Population: The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 16 | -0.62 scores on a scale | Standard Deviation 0.89 |
| All Participants | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 48 | -0.56 scores on a scale | Standard Deviation 1.252 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 48 | -1.36 scores on a scale | Standard Deviation 1.369 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 16 | -1.18 scores on a scale | Standard Deviation 1.717 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 16 | -0.62 scores on a scale | Standard Deviation 0.89 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 48 | -0.56 scores on a scale | Standard Deviation 1.252 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 16 | -1.06 scores on a scale | Standard Deviation 1.696 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 | Week 48 | -1.31 scores on a scale | Standard Deviation 1.324 |
Secondary
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48
The FEV1 was defined as the volume of air exhaled from the lungs in the first second of a forced expiration and was measured by spirometry. Baseline is the last non-missing measurement with acceptable quality prior to the first dose of study treatment.
Time frame: Baseline (Day 0) and at Weeks 16 and 48
Population: The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| All Participants | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 16 | -0.001 liters | Standard Deviation 0.2434 |
| All Participants | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 48 | 0.003 liters | Standard Deviation 0.3412 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 48 | 0.425 liters | Standard Deviation 0.4395 |
| Benralizumab Dose 2, Aged 6-11 Years | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 16 | -0.119 liters | Standard Deviation 0.2435 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 16 | -0.001 liters | Standard Deviation 0.2434 |
| Benralizumab Dose 1, Aged 6-14 Years | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 48 | 0.003 liters | Standard Deviation 0.3412 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 16 | -0.165 liters | Standard Deviation 0.2609 |
| Benralizumab Dose 2, Aged 6-14 Years | Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 | Week 48 | 0.428 liters | Standard Deviation 0.4209 |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab
Blood samples were analyzed for the presence of ADAs for benralizumab. ADA prevalence: ADA positive (+ve) at any time point including baseline and/or post baseline. Treatment induced ADA+ve: ADA negative (-ve) at baseline and post-baseline ADA+ve. Treatment-boosted ADA+ve: baseline +ve ADA titer that was boosted by \>4-fold or higher-level following study drug administration. Treatment-emergent ADA+ve: either treatment-induced ADA+ve or treatment-boosted ADA+ve. Persistently +ve ADA: having at least 2 post-baseline ADA+ve assessments with at least 16 weeks (112 days) between the first and last +ve assessments, or an ADA+ve result at the last available assessment. Transiently +ve ADA: having at least 1 post-baseline ADA+ve assessment(s) and not persistently ADA+ve. Neutralizing antibodies (nAb) prevalence: nAb+ve at baseline and/or post-baseline. Treatment-induced nAb+ve (nAb incidence): nAb-ve at baseline (or ADA-ve at baseline) and nAb+ve at any post-baseline visit.
Time frame: Pre-dose at Baseline (Day 0), Weeks 8, 16 and 24 and post-dose at Week 48; and at early discontinuation or withdrawal visit
Population: The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab. Only those participants with data available were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Transiently ADA+ve | 2 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Persistently ADA+ve | 1 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb incidence | 3 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Baseline and at least 1 post-baseline ADA+ve | 0 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Post-baseline ADA+ve | 3 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Treatment-emergent ADA+ve | 3 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb prevalence | 3 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Only baseline ADA+ve | 0 Participants |
| All Participants | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | ADA prevalence | 3 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Only baseline ADA+ve | 0 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Transiently ADA+ve | 1 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Persistently ADA+ve | 0 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Treatment-emergent ADA+ve | 1 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | ADA prevalence | 1 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Post-baseline ADA+ve | 1 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb incidence | 1 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb prevalence | 1 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Baseline and at least 1 post-baseline ADA+ve | 0 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Only baseline ADA+ve | 0 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | ADA prevalence | 3 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Treatment-emergent ADA+ve | 3 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Post-baseline ADA+ve | 3 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Baseline and at least 1 post-baseline ADA+ve | 0 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Persistently ADA+ve | 1 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Transiently ADA+ve | 2 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb prevalence | 3 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb incidence | 3 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Transiently ADA+ve | 1 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Baseline and at least 1 post-baseline ADA+ve | 0 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Post-baseline ADA+ve | 1 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb incidence | 1 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | nAb prevalence | 1 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Treatment-emergent ADA+ve | 1 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Persistently ADA+ve | 0 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | Only baseline ADA+ve | 0 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab | ADA prevalence | 1 Participants |
Secondary
Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires
The PGIC-IA and CGIC instruments were used for an overall evaluation of response to treatment, conducted separately by the Investigator and by the participant (administered by trained individuals to help the child understand the question and response options), using a 7-point scale: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse. The Investigator (clinician) and the participant were asked to rate the degree of change in the overall asthma status compared to the start of study treatment visit. Participants were defined as responders based on categorized responses for PGIC-IA and CGIC. Responder status categories included Improved=Very much improved, Much improved, Minimally improved, Much improved=Much improved, Very much improved, Very much improved=Very much improved. CGIC = PGIC-IA indicates agreement between CGIC and PGIC-IA assessments of response to treatment at the same visit.
Time frame: At Weeks 16 and 48; and at early discontinuation or withdrawal visit
Population: The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, very much improved | 3 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, improved | 15 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, much improved | 7 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, much improved | 8 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, improved | 13 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, very much improved | 5 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, improved | 10 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, improved | 13 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, much improved | 5 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, much improved | 9 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, much improved | 10 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, very much improved | 9 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, improved | 13 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, improved | 9 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, much improved | 8 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, very much improved | 5 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, very much improved | 3 Participants |
| All Participants | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, very much improved | 4 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, much improved | 10 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, very much improved | 5 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, improved | 13 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, very much improved | 8 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, much improved | 5 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, very much improved | 4 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, much improved | 11 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, very much improved | 9 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, improved | 6 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, much improved | 10 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, very much improved | 6 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, much improved | 7 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, improved | 8 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, much improved | 9 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, improved | 12 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, very much improved | 6 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, improved | 11 Participants |
| Benralizumab Dose 2, Aged 6-11 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, improved | 12 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, improved | 9 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, improved | 13 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, much improved | 10 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, very much improved | 4 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, improved | 13 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, much improved | 9 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, very much improved | 9 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, improved | 13 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, much improved | 8 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, very much improved | 3 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, improved | 15 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, much improved | 8 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, very much improved | 5 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, improved | 10 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, much improved | 7 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, very much improved | 3 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, much improved | 5 Participants |
| Benralizumab Dose 1, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, very much improved | 5 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, much improved | 11 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, much improved | 5 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, very much improved | 5 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, much improved | 9 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, improved | 13 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, very much improved | 4 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 16, improved | 12 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, very much improved | 10 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, much improved | 11 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, improved | 8 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 48, improved | 13 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | PGIC-IA, Week 16, very much improved | 9 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, very much improved | 6 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, very much improved | 6 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, much improved | 12 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 48, much improved | 7 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC = PGIC-IA, Week 16, improved | 6 Participants |
| Benralizumab Dose 2, Aged 6-14 Years | Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires | CGIC, Week 48, improved | 14 Participants |