Trial · NCT04305405

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

NCT04305405, Phase 3, Completed, AstraZeneca; results first posted 2023-05-18

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. PK/PD and Long Term Safety Study of Benralizumab in Children With Severe Eosinophilic Asthma. Trials, record NCT04305405. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04305405

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: PK/PD and Long Term Safety Study of Benralizumab in Children With Severe Eosinophilic Asthma
NCT number: NCT04305405
Status: Completed
Phases: Phase 3
Enrollment: 30 participants, actual
Lead sponsor: AstraZeneca
Conditions: Severe Uncontrolled Asthma
Interventions: Benralizumab
First posted: 2020-03-12
Last updated: 2023-05-18
Results first posted: 2023-05-18

Source ClinicalTrials.gov

Registered outcomes12

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Primary	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.
Secondary	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.
Secondary	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.
Secondary	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.

1 to 10 of 12Source ClinicalTrials.gov

See all 12 registered outcomes

Outcomes12

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	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	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.	liter (L) per day	MEAN
PRIMARY	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	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.	nanogramday per milliliter (ngday/mL)	GEOMETRIC_MEAN
PRIMARY	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	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.	ng/mL	GEOMETRIC_MEAN
PRIMARY	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	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.	day	MEDIAN
PRIMARY	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	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.	day	MEDIAN
PRIMARY	Trough Concentration of Benralizumab at Week 16 (Ctrough16)	Pre-dose on Day 112	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.	ng/mL	GEOMETRIC_MEAN
PRIMARY	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	The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab. Only those participants with data available were analyzed.	cells/microliters	MEAN
SECONDARY	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	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.	L/day/kilogram	MEAN
SECONDARY	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	The Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab. Only those participants with data available were analyzed.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	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 Safety Analysis set consisted of all participants who received at least 1 dose of benralizumab. Only those participants with data available were analyzed.	liters	MEAN

1 to 10 of 12Source ClinicalTrials.gov

See all 12 outcomes

Results by group167

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Value	Spread	Units
Clearance of Benralizumab	All Participants	0.156	Standard Deviation 0.0598	liter (L) per day
Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab	Benralizumab Dose 1, Aged 6-11 Years	36918.01	Geometric Coefficient of Variation 24.61	nanogramday per milliliter (ngday/mL)
Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab	Benralizumab Dose 2, Aged 6-11 Years	75593.37	Geometric Coefficient of Variation 39.96	nanogramday per milliliter (ngday/mL)
Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab	Benralizumab Dose 1, Aged 6-14 Years	36918.01	Geometric Coefficient of Variation 24.61	nanogramday per milliliter (ngday/mL)
Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab	Benralizumab Dose 2, Aged 6-14 Years	73670.51	Geometric Coefficient of Variation 38.86	nanogramday per milliliter (ngday/mL)
Maximum Observed Serum Concentration (Cmax) of Benralizumab	Benralizumab Dose 1, Aged 6-11 Years	1901.18	Geometric Coefficient of Variation 28.42	ng/mL
Maximum Observed Serum Concentration (Cmax) of Benralizumab	Benralizumab Dose 2, Aged 6-11 Years	3118.69	Geometric Coefficient of Variation 47.35	ng/mL
Maximum Observed Serum Concentration (Cmax) of Benralizumab	Benralizumab Dose 1, Aged 6-14 Years	1901.18	Geometric Coefficient of Variation 28.42	ng/mL
Maximum Observed Serum Concentration (Cmax) of Benralizumab	Benralizumab Dose 2, Aged 6-14 Years	3090.85	Geometric Coefficient of Variation 43.66	ng/mL
Terminal Phase Elimination Half-Life (t1/2) of Benralizumab	All Participants	14.4	Full Range 6.94 to 23.4	day

1 to 10 of 167Source ClinicalTrials.gov

See all 167 results by group

Participant flow6

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Benralizumab Dose 1, Aged 6-14 Years	15
Overall Study	STARTED	Benralizumab Dose 2, Aged 6-14 Years	15
Overall Study	COMPLETED	Benralizumab Dose 1, Aged 6-14 Years	15
Overall Study	COMPLETED	Benralizumab Dose 2, Aged 6-14 Years	14
Overall Study	NOT COMPLETED	Benralizumab Dose 1, Aged 6-14 Years	0
Overall Study	NOT COMPLETED	Benralizumab Dose 2, Aged 6-14 Years	1

Source ClinicalTrials.gov

Adverse events232

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Gastritis	Gastrointestinal disorders	Benralizumab Dose 1, Aged 6-11 Years	0	15	0
other	Gastritis	Gastrointestinal disorders	Benralizumab Dose 2, Aged 6-11 Years	0	13	0
other	Gastritis	Gastrointestinal disorders	Benralizumab Dose 1, Aged 6-14 Years	0	15	0
other	Gastritis	Gastrointestinal disorders	Benralizumab Dose 2, Aged 6-14 Years	1	15	1
other	Gastrooesophageal reflux disease	Gastrointestinal disorders	Benralizumab Dose 1, Aged 6-11 Years	0	15	0
other	Gastrooesophageal reflux disease	Gastrointestinal disorders	Benralizumab Dose 2, Aged 6-11 Years	0	13	0
other	Gastrooesophageal reflux disease	Gastrointestinal disorders	Benralizumab Dose 1, Aged 6-14 Years	0	15	0
other	Gastrooesophageal reflux disease	Gastrointestinal disorders	Benralizumab Dose 2, Aged 6-14 Years	1	15	1
other	Vomiting	Gastrointestinal disorders	Benralizumab Dose 1, Aged 6-11 Years	2	15	2
other	Vomiting	Gastrointestinal disorders	Benralizumab Dose 2, Aged 6-11 Years	0	13	0

1 to 10 of 232Source ClinicalTrials.gov

See all 232 adverse events

Adverse event totals12

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	Benralizumab Dose 1, Aged 6-11 Years	0	15
Total, all-cause mortality	Benralizumab Dose 2, Aged 6-11 Years	0	13
Total, all-cause mortality	Benralizumab Dose 1, Aged 6-14 Years	0	15
Total, all-cause mortality	Benralizumab Dose 2, Aged 6-14 Years	0	15
Total, other adverse events	Benralizumab Dose 1, Aged 6-11 Years	13	15
Total, other adverse events	Benralizumab Dose 2, Aged 6-11 Years	9	13
Total, other adverse events	Benralizumab Dose 1, Aged 6-14 Years	13	15
Total, other adverse events	Benralizumab Dose 2, Aged 6-14 Years	11	15
Total, serious adverse events	Benralizumab Dose 1, Aged 6-11 Years	1	15
Total, serious adverse events	Benralizumab Dose 2, Aged 6-11 Years	2	13

1 to 10 of 12Source ClinicalTrials.gov

See all 12 adverse event totals

Papers1

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as
38491795	DERIVED

Source PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

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