Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma

Conditions

Asthma

Keywords

Mild asthma, Moderate asthma, Severe asthma

Brief summary

This study will evaluate the pharmacokinetic (PK) profile of a single subcutaneous (SC) dose of tezepelumab in children aged ≥ 5 to 11 years with asthma.

Anna Lundahl, J Grigg, Lubna Abuqayyas, Piotr Kuna, Gillian Hunter et al. (15 authors)

British Journal of Clinical Pharmacology2026-07-06

10.1002/bcp.70666

Interventions

BIOLOGICALTezepelumab

Single dose subcutaneous injection

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

BASIC_SCIENCE

Masking

NONE

Masking description

No masking is used. All involved know the identity of the intervention assignment.

Eligibility

Sex/Gender

ALL

Age

5 Years to 11 Years

Healthy volunteers

No

Inclusion criteria

* Written informed consent and written informed assent and any locally required authorisation obtained from the subject and legal representative prior to any study related procedure taking place. * Age 5 to 11 years (inclusive) at Visit 1 and Visit 2 (Day 1). Type of Subject and Disease Characteristics * Documented physician diagnosed asthma for at least 6 months prior to Visit 1. * Documented treatment with total daily dose of either low, medium, or high dose ICS for at least 6 months, as described in Step 2 to Step 4 of GINA guidelines (GINA 2020) with stable dose for at least 3 months prior to Visit 1. * Pre bronchodilator (BD) FEV1 of ≥ 50% of predicted normal value at Visit 1 * Body weight ≥ 16 kg at Visit 1 and Visit 2 (Day 1).

Exclusion criteria

* History of any clinically significant disease or disorder other than asthma which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. * History of a deterioration in asthma or asthma exacerbation that required a burst of systemic corticosteroids within 6 weeks of Visit 1, up to and including Visit 2 (Day 1). * History of hospitalisation (overnight admission) for asthma within 3 months of Visit 1, up to and including Visit 2 (Day 1). * History of a life threatening asthma exacerbation requiring intubation or mechanical ventilation. * History of systemic corticosteroid use for the maintenance treatment of asthma within 6 weeks of Visit 1, up to and including Visit 2 (Day 1) and discouraged until EOS. * History of cancer. * History of hypersensitivity or anaphylactic reaction to any biologic therapy.

Design outcomes

Primary

Measure	Time frame	Description
Apparent Volume of Distribution (Vz/F) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the Vz/F of tezepelumab and estimated as CL/F\*1/ λZ. The PK parameters were estimated using non-compartmental analysis method.
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the tmax of tezepelumab. The PK parameters were estimated using non-compartmental analysis method.
Maximum Observed Serum Concentration (Cmax) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the Cmax of tezepelumab. The Pharmacokinetic (PK) parameters were estimated using non-compartmental analysis method.
Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the AUC0-last of tezepelumab and calculated by linear up/log down trapezoidal summation. The PK parameters were estimated using non-compartmental analysis method.
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the AUC0-inf of tezepelumab and calculated by linear up/log down trapezoidal summation and extrapolated to infinity by the addition of the last quantifiable concentration divided by the terminal rate constant. The PK parameters were estimated using non-compartmental analysis method.
Terminal Phase Elimination Half-Life (t1/2) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the t1/2 of tezepelumab and calculated as ln(2)/λZ, where λZ is the first-order rate constant associated with the terminal (log-linear) elimination phase. The PK parameters were estimated using non-compartmental analysis method.
Apparent Clearance (CL/F) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the CL/F of tezepelumab and estimated as dose divided by AUC0-inf. The PK parameters were estimated using non-compartmental analysis method.
Apparent Steady-State Volume of Distribution (Vss/F) of Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85	Blood samples were collected to determine the Vss/F of tezepelumab and estimated as CL/F\*mean residence time (MRT), where MRT=Area under the moment curve of the analyte in the sampled matrix from zero (predose) extrapolated to infinite time/(AUC0-inf). The PK parameters were estimated using non-compartmental analysis method.

Secondary

Measure	Time frame	Description
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab	Predose and within ± 1 hour of postdose on Day 1; on Days 29 and 85	Blood samples were analyzed for the presence of ADAs for tezepelumab using validated assays. ADA prevalence was defined as ADA positive at baseline and/or post baseline. ADA incidence was defined as the percentage of treatment-emergent ADA positive participants in a population. Treatment induced ADA positive was defined as ADA negative at baseline and post-baseline ADA positive. Treatment-boosted ADA positive was defined as baseline positive ADA titre that was boosted to a 4-fold or higher level following study drug administration. Treatment-emergent ADA positive was defined as either treatment-induced ADA positive or treatment-boosted ADA positive.

Countries

Hungary, South Africa, United Kingdom

Participant flow

Recruitment details

This Phase I open-label study was conducted in pediatric participants with mild, moderate, or severe asthma at 6 investigational sites in the UK, Hungary, and South Africa between 23 February 2021 and 27 September 2022.

Pre-assignment details

This study consists a screening period (14 days), and a single dose treatment (Day 1) and follow-up period (85 days). A total of 18 participants were treated in the study.

Participants by arm

Arm	Count
Tezepelumab Participants received a single dose of tezepelumab SC injection on Day 1.	18
Total	18

Baseline characteristics

Characteristic	Tezepelumab
Age, Continuous	7.9 years STANDARD_DEVIATION 1.78
Race/Ethnicity, Customized Asian	2 Participants
Race/Ethnicity, Customized Black or African American	1 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	18 Participants
Race/Ethnicity, Customized Other	9 Participants
Race/Ethnicity, Customized White	6 Participants
Sex: Female, Male Female	7 Participants
Sex: Female, Male Male	11 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 18
other Total, other adverse events	7 / 18
serious Total, serious adverse events	0 / 18

Outcome results

Primary

Apparent Clearance (CL/F) of Tezepelumab

Blood samples were collected to determine the CL/F of tezepelumab and estimated as dose divided by AUC0-inf. The PK parameters were estimated using non-compartmental analysis method.