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NCT04305405: TATE

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

Completed Phase 3 Results posted Last updated 18 May 2023
What this trial tests

Phase 3 trial testing Benralizumab in Severe Uncontrolled Asthma in 30 participants. Completed in 12 September 2022.

Timeline
21 November 2019
Primary endpoint
12 September 2022
12 September 2022

Quick facts

Lead sponsorAstraZeneca
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposebasic science
Enrollment30
Start date21 November 2019
Primary completion12 September 2022
Estimated completion12 September 2022
Sites15 locations across Japan, United States

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 6 to 14, any sex, with Severe Uncontrolled Asthma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clearance of Benralizumab Primary · 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.

GroupValue95% CI
All Participants0.156± 0.0598
Area Under the Serum Concentration-Time Curve From Time Zero to Day 28 (AUC0-28) of Benralizumab Primary · 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.

GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years36918.01± 24.61
Benralizumab Dose 2, Aged 6-11 Years75593.37± 39.96
Benralizumab Dose 1, Aged 6-14 Years36918.01± 24.61
Benralizumab Dose 2, Aged 6-14 Years73670.51± 38.86
Maximum Observed Serum Concentration (Cmax) of Benralizumab Primary · 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.

GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years1901.18± 28.42
Benralizumab Dose 2, Aged 6-11 Years3118.69± 47.35
Benralizumab Dose 1, Aged 6-14 Years1901.18± 28.42
Benralizumab Dose 2, Aged 6-14 Years3090.85± 43.66
Terminal Phase Elimination Half-Life (t1/2) of Benralizumab Primary · 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.

GroupValue95% CI
All Participants14.46.94 – 23.4
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Benralizumab Primary · 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.

GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years6.910.93 – 14.95
Benralizumab Dose 2, Aged 6-11 Years7.261.10 – 14.01
Benralizumab Dose 1, Aged 6-14 Years6.910.93 – 14.95
Benralizumab Dose 2, Aged 6-14 Years7.941.10 – 14.01
Trough Concentration of Benralizumab at Week 16 (Ctrough16) Primary · 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.

GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years142.42± 256.34
Benralizumab Dose 2, Aged 6-11 Years339.35± 409.24
Benralizumab Dose 1, Aged 6-14 Years142.42± 256.34
Benralizumab Dose 2, Aged 6-14 Years340.46± 363.69
Change From Baseline in Peripheral Blood Eosinophil Count up to Week 48 Primary · 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.

Week 4
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-447.3± 283.76
Benralizumab Dose 2, Aged 6-11 Years-436.9± 408.28
Benralizumab Dose 1, Aged 6-14 Years-447.3± 283.76
Benralizumab Dose 2, Aged 6-14 Years-455.3± 385.58
Week 8
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-445.3± 276.20
Benralizumab Dose 2, Aged 6-11 Years-453.8± 396.03
Benralizumab Dose 1, Aged 6-14 Years-445.3± 276.20
Benralizumab Dose 2, Aged 6-14 Years-470.7± 374.25
Week 12
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-443.3± 286.85
Benralizumab Dose 2, Aged 6-11 Years-455.8± 419.32
Benralizumab Dose 1, Aged 6-14 Years-443.3± 286.85
Benralizumab Dose 2, Aged 6-14 Years-472.9± 393.49
Week 16
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-446.7± 279.12
Benralizumab Dose 2, Aged 6-11 Years-402.7± 384.61
Benralizumab Dose 1, Aged 6-14 Years-446.7± 279.12
Benralizumab Dose 2, Aged 6-14 Years-430.0± 378.68
Week 24
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-354.2± 323.99
Benralizumab Dose 2, Aged 6-11 Years-436.9± 405.90
Benralizumab Dose 1, Aged 6-14 Years-354.2± 323.99
Benralizumab Dose 2, Aged 6-14 Years-457.9± 397.77
Week 48
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-434.0± 286.15
Benralizumab Dose 2, Aged 6-11 Years-453.8± 392.78
Benralizumab Dose 1, Aged 6-14 Years-434.0± 286.15
Benralizumab Dose 2, Aged 6-14 Years-474.3± 385.04
Body Weight-Adjusted Clearance of Benralizumab Secondary · 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.

GroupValue95% CI
All Participants0.00408± 0.000764
Number of Participants With Anti-Drug Antibodies (ADA) Response to Benralizumab Secondary · 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

ADA prevalence
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years3
Benralizumab Dose 2, Aged 6-11 Years1
Benralizumab Dose 1, Aged 6-14 Years3
Benralizumab Dose 2, Aged 6-14 Years1
Treatment-emergent ADA+ve
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years3
Benralizumab Dose 2, Aged 6-11 Years1
Benralizumab Dose 1, Aged 6-14 Years3
Benralizumab Dose 2, Aged 6-14 Years1
Post-baseline ADA+ve
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years3
Benralizumab Dose 2, Aged 6-11 Years1
Benralizumab Dose 1, Aged 6-14 Years3
Benralizumab Dose 2, Aged 6-14 Years1
Baseline and at least 1 post-baseline ADA+ve
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years0
Benralizumab Dose 2, Aged 6-11 Years0
Benralizumab Dose 1, Aged 6-14 Years0
Benralizumab Dose 2, Aged 6-14 Years0
Only baseline ADA+ve
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years0
Benralizumab Dose 2, Aged 6-11 Years0
Benralizumab Dose 1, Aged 6-14 Years0
Benralizumab Dose 2, Aged 6-14 Years0
Persistently ADA+ve
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years1
Benralizumab Dose 2, Aged 6-11 Years0
Benralizumab Dose 1, Aged 6-14 Years1
Benralizumab Dose 2, Aged 6-14 Years0
Transiently ADA+ve
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years2
Benralizumab Dose 2, Aged 6-11 Years1
Benralizumab Dose 1, Aged 6-14 Years2
Benralizumab Dose 2, Aged 6-14 Years1
nAb prevalence
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years3
Benralizumab Dose 2, Aged 6-11 Years1
Benralizumab Dose 1, Aged 6-14 Years3
Benralizumab Dose 2, Aged 6-14 Years1
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) up to Week 48 Secondary · 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.

Week 16
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-0.001± 0.2434
Benralizumab Dose 2, Aged 6-11 Years-0.119± 0.2435
Benralizumab Dose 1, Aged 6-14 Years-0.001± 0.2434
Benralizumab Dose 2, Aged 6-14 Years-0.165± 0.2609
Week 48
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years0.003± 0.3412
Benralizumab Dose 2, Aged 6-11 Years0.425± 0.4395
Benralizumab Dose 1, Aged 6-14 Years0.003± 0.3412
Benralizumab Dose 2, Aged 6-14 Years0.428± 0.4209
Change From Baseline in Interviewer-Administered Asthma Control Questionnaire (ACQ-IA) Score up to Week 48 Secondary · 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

Week 16
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-0.62± 0.890
Benralizumab Dose 2, Aged 6-11 Years-1.18± 1.717
Benralizumab Dose 1, Aged 6-14 Years-0.62± 0.890
Benralizumab Dose 2, Aged 6-14 Years-1.06± 1.696
Week 48
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years-0.56± 1.252
Benralizumab Dose 2, Aged 6-11 Years-1.36± 1.369
Benralizumab Dose 1, Aged 6-14 Years-0.56± 1.252
Benralizumab Dose 2, Aged 6-14 Years-1.31± 1.324
Number of Responders in Interviewer-Administered Patient Global Impression of Change (PGIC)-IA and Clinician Global Impression of Change (CGIC) Questionnaires Secondary · 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 de

PGIC-IA, Week 16, improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years13
Benralizumab Dose 2, Aged 6-11 Years12
Benralizumab Dose 1, Aged 6-14 Years13
Benralizumab Dose 2, Aged 6-14 Years13
PGIC-IA, Week 16, much improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years10
Benralizumab Dose 2, Aged 6-11 Years10
Benralizumab Dose 1, Aged 6-14 Years10
Benralizumab Dose 2, Aged 6-14 Years11
PGIC-IA, Week 16, very much improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years4
Benralizumab Dose 2, Aged 6-11 Years8
Benralizumab Dose 1, Aged 6-14 Years4
Benralizumab Dose 2, Aged 6-14 Years9
PGIC-IA, Week 48, improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years13
Benralizumab Dose 2, Aged 6-11 Years12
Benralizumab Dose 1, Aged 6-14 Years13
Benralizumab Dose 2, Aged 6-14 Years13
PGIC-IA, Week 48, much improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years9
Benralizumab Dose 2, Aged 6-11 Years10
Benralizumab Dose 1, Aged 6-14 Years9
Benralizumab Dose 2, Aged 6-14 Years11
PGIC-IA, Week 48, very much improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years9
Benralizumab Dose 2, Aged 6-11 Years9
Benralizumab Dose 1, Aged 6-14 Years9
Benralizumab Dose 2, Aged 6-14 Years10
CGIC, Week 16, improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years13
Benralizumab Dose 2, Aged 6-11 Years11
Benralizumab Dose 1, Aged 6-14 Years13
Benralizumab Dose 2, Aged 6-14 Years12
CGIC, Week 16, much improved
GroupValue95% CI
Benralizumab Dose 1, Aged 6-11 Years8
Benralizumab Dose 2, Aged 6-11 Years9
Benralizumab Dose 1, Aged 6-14 Years8
Benralizumab Dose 2, Aged 6-14 Years9

Adverse events — posted to ClinicalTrials.gov

Time frame: 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. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Benralizumab Dose 1, Aged 6-11 Years
Serious: 1/15 (7%)
Deaths: 0/15
Benralizumab Dose 2, Aged 6-11 Years
Serious: 2/13 (15%)
Deaths: 0/13
Benralizumab Dose 1, Aged 6-14 Years
Serious: 1/15 (7%)
Deaths: 0/15
Benralizumab Dose 2, Aged 6-14 Years
Serious: 4/15 (27%)
Deaths: 0/15

Serious adverse events (2 terms)

ReactionSystemBenralizumab Dose 1, Aged …Benralizumab Dose 2, Aged …Benralizumab Dose 1, Aged …Benralizumab Dose 2, Aged …
AsthmaRespiratory, thoracic and mediastinal disorders
Somatic symptom disorderPsychiatric disorders
Other adverse events (56 terms — click to expand)

ReactionSystemBenralizumab Dose 1, Aged …Benralizumab Dose 2, Aged …Benralizumab Dose 1, Aged …Benralizumab Dose 2, Aged …
NasopharyngitisInfections and infestations
PyrexiaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
COVID-19Infections and infestations
PneumoniaInfections and infestations
SinusitisInfections and infestations
Viral upper respiratory tract infectionInfections and infestations
Pain in extremityMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
UrticariaSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
GastritisGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
ChillsGeneral disorders
FatigueGeneral disorders
Injection site reactionGeneral disorders
Vaccination site painGeneral disorders
Allergy to animalImmune system disorders
Immunisation reactionImmune system disorders
AnaemiaBlood and lymphatic system disorders
Asymptomatic COVID-19Infections and infestations
BronchitisInfections and infestations
Bronchitis bacterialInfections and infestations
GastroenteritisInfections and infestations
Oral herpesInfections and infestations
PharyngitisInfections and infestations
Pharyngitis streptococcalInfections and infestations
PalpitationsCardiac disorders
Skin candidaInfections and infestations
Streptococcal infectionInfections and infestations
ContusionInjury, poisoning and procedural complications
Hand fractureInjury, poisoning and procedural complications
Ligament ruptureInjury, poisoning and procedural complications
Road traffic accidentInjury, poisoning and procedural complications
Blood thyroid stimulating hormone decreasedInvestigations
Occult blood positiveInvestigations
Abdominal painGastrointestinal disorders
DepressionPsychiatric disorders

Most-reported serious reactions: Asthma, Somatic symptom disorder.

Data from ClinicalTrials.gov NCT04305405 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Benralizumab in children with severe eosinophilic asthma: Pharmacokinetics and long-term safety (TATE study).
    Wedner HJ, Fujisawa T, Guilbert TW, Ikeda M, et al · · 2024 · cited 24× · PMID 38491795 · DOI 10.1111/pai.14092
  2. Biologics to Treat Severe Asthma in Children and Adolescents: A Practical Update.
    Marseglia GL, Licari A, Tosca MA, Ciprandi G. · · 2020 · cited 2× · PMID 35921565 · DOI 10.1089/ped.2020.1212

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