Trial Outcomes & Findings for PK/PD and Long Term Safety Study of Benralizumab in Children With Severe Eosinophilic Asthma (NCT NCT04305405)

Last Updated: 2023-05-18

Results Overview

Blood samples were collected to determine the clearance of benralizumab. This was an empirical Bayesian estimate (EBE) derived posthoc using population PK analysis.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

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

Results posted on

2023-05-18

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Benralizumab Dose 1, Aged 6-14 Years All participants with body weight \<35 kilograms (kg) at screening received benralizumab Dose 1 subcutaneous (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.	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.
Overall Study STARTED	15	15
Overall Study COMPLETED	15	14
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Benralizumab Dose 1, Aged 6-14 Years All participants with body weight \<35 kilograms (kg) at screening received benralizumab Dose 1 subcutaneous (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.	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.
Overall Study Withdrawal by parent/guardian	0	1

Baseline Characteristics

PK/PD and Long Term Safety Study of Benralizumab in Children With Severe Eosinophilic Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.	Total n=30 Participants Total of all reporting groups
Age, Continuous	8.3 years STANDARD_DEVIATION 2.02 • n=5 Participants	9.8 years STANDARD_DEVIATION 1.93 • n=7 Participants	9.0 years STANDARD_DEVIATION 2.09 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized White	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Asian	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Blood samples were collected to determine the clearance of benralizumab. This was an empirical Bayesian estimate (EBE) derived posthoc using population PK analysis.

Outcome measures

Outcome measures
Measure	All Participants n=30 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years Participants with body weight \>=35 kg 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.	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.	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.
Clearance of Benralizumab	0.156 liter (L) per day Standard Deviation 0.0598	—	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=10 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=10 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=10 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=11 Participants 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.
Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab	36918.01 nanogramday per milliliter (ngday/mL) Geometric Coefficient of Variation 24.61	75593.37 nanogramday per milliliter (ngday/mL) Geometric Coefficient of Variation 39.96	36918.01 nanogramday per milliliter (ngday/mL) Geometric Coefficient of Variation 24.61	73670.51 nanogramday per milliliter (ngday/mL) Geometric Coefficient of Variation 38.86

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.
Maximum Observed Serum Concentration (Cmax) of Benralizumab	1901.18 ng/mL Geometric Coefficient of Variation 28.42	3118.69 ng/mL Geometric Coefficient of Variation 47.35	1901.18 ng/mL Geometric Coefficient of Variation 28.42	3090.85 ng/mL Geometric Coefficient of Variation 43.66

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=30 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years Participants with body weight \>=35 kg 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.	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.	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.
Terminal Phase Elimination Half-Life (t1/2) of Benralizumab	14.4 day Interval 6.94 to 23.4	—	—	—

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab	6.91 day Interval 0.93 to 14.95	7.26 day Interval 1.1 to 14.01	6.91 day Interval 0.93 to 14.95	7.94 day Interval 1.1 to 14.01

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=14 Participants 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.
Trough Concentration of Benralizumab at Week 16 (Ctrough16)	142.42 ng/mL Geometric Coefficient of Variation 256.34	339.35 ng/mL Geometric Coefficient of Variation 409.24	142.42 ng/mL Geometric Coefficient of Variation 256.34	340.46 ng/mL Geometric Coefficient of Variation 363.69

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 Week 4	-447.3 cells/microliters Standard Deviation 283.76	-436.9 cells/microliters Standard Deviation 408.28	-447.3 cells/microliters Standard Deviation 283.76	-455.3 cells/microliters Standard Deviation 385.58
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 Week 8	-445.3 cells/microliters Standard Deviation 276.20	-453.8 cells/microliters Standard Deviation 396.03	-445.3 cells/microliters Standard Deviation 276.20	-470.7 cells/microliters Standard Deviation 374.25
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 Week 12	-443.3 cells/microliters Standard Deviation 286.85	-455.8 cells/microliters Standard Deviation 419.32	-443.3 cells/microliters Standard Deviation 286.85	-472.9 cells/microliters Standard Deviation 393.49
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 Week 16	-446.7 cells/microliters Standard Deviation 279.12	-402.7 cells/microliters Standard Deviation 384.61	-446.7 cells/microliters Standard Deviation 279.12	-430.0 cells/microliters Standard Deviation 378.68
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 Week 24	-354.2 cells/microliters Standard Deviation 323.99	-436.9 cells/microliters Standard Deviation 405.90	-354.2 cells/microliters Standard Deviation 323.99	-457.9 cells/microliters Standard Deviation 397.77
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 Week 48	-434.0 cells/microliters Standard Deviation 286.15	-453.8 cells/microliters Standard Deviation 392.78	-434.0 cells/microliters Standard Deviation 286.15	-474.3 cells/microliters Standard Deviation 385.04

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	All Participants n=30 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years Participants with body weight \>=35 kg 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.	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.	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.
Body Weight-Adjusted Clearance of Benralizumab	0.00408 L/day/kilogram Standard Deviation 0.000764	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab ADA prevalence	3 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab Treatment-emergent ADA+ve	3 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab Post-baseline ADA+ve	3 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab Baseline and at least 1 post-baseline ADA+ve	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab Only baseline ADA+ve	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab Persistently ADA+ve	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab Transiently ADA+ve	2 Participants	1 Participants	2 Participants	1 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab nAb prevalence	3 Participants	1 Participants	3 Participants	1 Participants
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab nAb incidence	3 Participants	1 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.
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	-0.119 liters Standard Deviation 0.2435	-0.001 liters Standard Deviation 0.2434	-0.165 liters Standard Deviation 0.2609
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	0.425 liters Standard Deviation 0.4395	0.003 liters Standard Deviation 0.3412	0.428 liters Standard Deviation 0.4209

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.
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 0.890	-1.18 scores on a scale Standard Deviation 1.717	-0.62 scores on a scale Standard Deviation 0.890	-1.06 scores on a scale Standard Deviation 1.696
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	-1.36 scores on a scale Standard Deviation 1.369	-0.56 scores on a scale Standard Deviation 1.252	-1.31 scores on a scale Standard Deviation 1.324

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=15 Participants All participants aged 6-14 years enrolled in this study irrespective of study treatment received were included in this arm.	Benralizumab Dose 2, Aged 6-11 Years n=13 Participants Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 Participants 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 Participants 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.
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	12 Participants	13 Participants	13 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	10 Participants	10 Participants	11 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	8 Participants	4 Participants	9 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	12 Participants	13 Participants	13 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	10 Participants	9 Participants	11 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	9 Participants	9 Participants	10 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	11 Participants	13 Participants	12 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	9 Participants	8 Participants	9 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	5 Participants	3 Participants	5 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	13 Participants	15 Participants	14 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	11 Participants	8 Participants	12 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	6 Participants	5 Participants	6 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	6 Participants	10 Participants	6 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	5 Participants	7 Participants	5 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	4 Participants	3 Participants	4 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	8 Participants	9 Participants	8 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	7 Participants	5 Participants	7 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	6 Participants	5 Participants	6 Participants

Adverse Events

Benralizumab Dose 1, Aged 6-11 Years

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Benralizumab Dose 2, Aged 6-11 Years

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

Benralizumab Dose 1, Aged 6-14 Years

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Benralizumab Dose 2, Aged 6-14 Years

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Benralizumab Dose 1, Aged 6-11 Years n=15 participants at risk 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.	Benralizumab Dose 2, Aged 6-11 Years n=13 participants at risk Participants with body weight \>=35 kg 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.	Benralizumab Dose 1, Aged 6-14 Years n=15 participants at risk All participants with a 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.	Benralizumab Dose 2, Aged 6-14 Years n=15 participants at risk All participants with a 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.
Psychiatric disorders Somatic symptom disorder	0.00% 0/15 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.	0.00% 0/13 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.	0.00% 0/15 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.
Respiratory, thoracic and mediastinal disorders Asthma	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.	15.4% 2/13 • Number of events 2 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.	6.7% 1/15 • Number of events 1 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.	26.7% 4/15 • Number of events 4 • Treatment-emergent adverse events were collected from the start of study drug administration (Day 1) until end of follow-up, approximately up to Week 53 The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab.

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place