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NCT04673630: TRAILHEAD

Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma

Completed Phase 1 Results posted Last updated 8 January 2024
What this trial tests

Phase 1 trial testing Tezepelumab in Asthma in 18 participants. Completed in 27 September 2022.

Timeline
23 February 2021
Primary endpoint
27 September 2022
27 September 2022

Quick facts

Lead sponsorAstraZeneca
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposebasic science
Enrollment18
Start date23 February 2021
Primary completion27 September 2022
Estimated completion27 September 2022
Sites6 locations across South Africa, United Kingdom, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 5 to 11, any sex, with 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.

Maximum Observed Serum Concentration (Cmax) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab27.1± 11.9
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab3.471.92 – 9.96
Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab872± 285
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab974± 320
Terminal Phase Elimination Half-Life (t1/2) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab25.7± 5.94
Apparent Clearance (CL/F) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab0.0802± 0.0295
Apparent Steady-State Volume of Distribution (Vss/F) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab3.08± 1.32
Apparent Volume of Distribution (Vz/F) of Tezepelumab Primary · 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.

GroupValue95% CI
Tezepelumab2.98± 1.26
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Secondary · 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 treatmen

ADA prevalence
GroupValue95% CI
Tezepelumab3
Only baseline ADA positive
GroupValue95% CI
Tezepelumab2
Baseline and at least 1 post-baseline ADA positive
GroupValue95% CI
Tezepelumab1
Baseline ADA positive regardless of post-baseline
GroupValue95% CI
Tezepelumab3
Any post-baseline ADA positive
GroupValue95% CI
Tezepelumab1
Treatment-induced ADA positive
GroupValue95% CI
Tezepelumab0
Treatment-boosted ADA positive
GroupValue95% CI
Tezepelumab0
Treatment-emergent ADA positive
GroupValue95% CI
Tezepelumab0

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Tezepelumab
Serious: 0/18 (0%)
Deaths: 0/18
Other adverse events (12 terms — click to expand)

ReactionSystemTezepelumab
COVID-19Infections and infestations
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
Viral upper respiratory tract infectionInfections and infestations
AsthmaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Seasonal allergyImmune system disorders
ContusionInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Pain in extremityMusculoskeletal and connective tissue disorders

Data from ClinicalTrials.gov NCT04673630 adverse events section.

Sponsor's own description

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.

Publications & conference data

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

  1. Role of thymic stromal lymphopoietin in allergy and beyond.
    Ebina-Shibuya R, Leonard WJ. · · 2023 · cited 181× · PMID 35650271 · DOI 10.1038/s41577-022-00735-y
  2. Targeting the Epithelium-Derived Innate Cytokines: From Bench to Bedside.
    Ham J, Shin JW, Ko BC, Kim HY. · · 2022 · cited 21× · PMID 35291657 · DOI 10.4110/in.2022.22.e11
  3. Severe Asthma and Biological Therapies: Now and the Future.
    Sardon-Prado O, Diaz-Garcia C, Corcuera-Elosegui P, Korta-Murua J, et al · · 2023 · cited 13× · PMID 37762787 · DOI 10.3390/jcm12185846
  4. Dupilumab and tezepelumab in severe refractory asthma: new opportunities.
    Ragnoli B, Morjaria J, Pignatti P, Montuschi P, et al · · 2022 · cited 7× · PMID 35655942 · DOI 10.1177/20406223221097327
  5. Safety of biologics for the treatment of asthma in children and adolescents: a systematic review.
    Wirthgen E, Quickert S, Weitzel J, Salewski B, et al · · 2025 · cited 1× · PMID 40533100 · DOI 10.1183/16000617.0269-2024
  6. Anti-alarmin asthma therapies: where do we go from here?
    Sulaiman I, Gauvreau GM. · · 2023 · cited 1× · PMID 37493796 · DOI 10.36416/1806-3756/e20230220

Verify or expand the search:

Other trials of Tezepelumab

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Other AstraZeneca trials

Trials by the same sponsor.

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