AsthmaPhase 1TRAILHEADNCT04673630

Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma

A Phase 1 study testing Tezepelumab in people with Asthma, run by AstraZeneca at 6 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 5 to 11 years
Conditions the study is for: Asthma
What is being tested?: Tezepelumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 6 sitesin 3 countries
Study dates: 23 Feb 2021to 27 Sep 2022
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 5 to 11 years
All sexes
No healthy volunteers
Child

Who may be able to join

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).

Who cannot join

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.

Trial locations and contacts

6 sites in 3 countries.

Country

City, postcode or hospital

6 sites in 3 countries

United Kingdom4 sites

Research Site
Bristol, BS2 8BJ
Research Site
Glasgow, G51 4TF
Research Site
London, E1 1BB
Research Site
London, SE5 9RS

Other trials in United Kingdom

Hungary1 site

Research Site
Budapest, 1094

Other trials in Hungary

South Africa1 site

Research Site
Cape Town, 7700

Other trials in South Africa

About this study

Official title: A Phase I, Open-label Study to Evaluate the Pharmacokinetics of Tezepelumab in Children ≥ 5 to 11 Years of Age With Mild, Moderate, or Severe Asthma (TRAILHEAD)

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.

Conditions: Asthma
Being tested: Tezepelumab
Keywords: Mild asthma, Moderate asthma, Severe asthma
Medical subject headings: Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TezepelumabBiological
Single dose subcutaneous injection

Study groups in NCT04673630
Study group	Role	What they receive
Tezepelumab	Experimental	Tezepelumab subcutaneous injection Receives: Biological: Tezepelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Serum Concentration (Cmax) of Tezepelumab
Blood samples were collected to determine the Cmax of tezepelumab. The Pharmacokinetic (PK) parameters were estimated using non-compartmental analysis method.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Tezepelumab
Blood samples were collected to determine the tmax of tezepelumab. The PK parameters were estimated using non-compartmental analysis method.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab
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.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tezepelumab
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.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Terminal Phase Elimination Half-Life (t1/2) of Tezepelumab
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.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Apparent Steady-State Volume of Distribution (Vss/F) of Tezepelumab
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.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Apparent Volume of Distribution (Vz/F) of Tezepelumab
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.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Secondary outcomes (1)

Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab
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.
Measured: Predose and within ± 1 hour of postdose on Day 1; on Days 29 and 85

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Feb 202127 Sep 2022

First posted17 Dec 2020
Study start23 Feb 2021
Primary completion27 Sep 2022
Study completion27 Sep 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04673630
Sponsor's protocol ID: D5180C00025
Acronym: TRAILHEAD
Status last verified: Mar 2023
First submitted: 2 Dec 2020
Last updated: 8 Jan 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Asthma trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-label Study to Evaluate the Pharmacokinetics of Tezepelumab in Children ≥ 5 to 11 Years of Age With Mild, Moderate, or Severe Asthma (TRAILHEAD)
ClinicalTrials.gov ID: NCT04673630
Acronym / sponsor ID: TRAILHEAD / D5180C00025
Conditions: Asthma
Keywords: Mild asthma, Moderate asthma, Severe asthma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Collaborators: Amgen
Study start: 23 Feb 2021 (actual)
Primary completion: 27 Sep 2022 (actual)
Study completion: 27 Sep 2022 (actual)
First posted: 17 Dec 2020 (actual)
Results: Posted 8 Jan 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Basic science
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Tezepelumab	Experimental	Biological: TezepelumabTezepelumab subcutaneous injection

Who may qualify

Ages: 5 to 11 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

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

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TezepelumabSingle dose subcutaneous injection	Biological	Tezepelumab

Primary outcome

Maximum Observed Serum Concentration (Cmax) of Tezepelumab
Time frame: 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.
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Tezepelumab
Time frame: 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.
Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Apparent Volume of Distribution (Vz/F) of Tezepelumab
Time frame: 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.

1 secondary outcome

Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab
Time frame: Predose and within ± 1 hour of postdose on Day 1; on Days 29 and 85

Results and safety

Results posted to the registry on 8 Jan 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Tezepelumab	18	18

Primary outcome: Maximum Observed Serum Concentration (Cmax) of Tezepelumab

Time frame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85. Mean (Standard Deviation). Unit: microgram per milliliter (mcg/mL)

Measure	Tezepelumab n = 18
Value	27.1 (11.9)

Population analysed: The PK analysis set included participants in the Safety Analysis set that had at least 1 detectable tezepelumab serum concentration from a sample collected postdose that was assumed not to be affected by factors such as important protocol deviations (eg, incorrect dose of study drug received).

Primary outcome: Time to Achieve Maximum Observed Serum Concentration (Tmax) of Tezepelumab

Time frame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85. Median (Full Range). Unit: day

Measure	Tezepelumab n = 18
Value	3.47 (1.92 to 9.96)

Primary outcome: Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab

Time frame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85. Mean (Standard Deviation). Unit: day*mcg/mL

Measure	Tezepelumab n = 18
Value	872 (285)

Primary outcome: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tezepelumab

Time frame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85. Mean (Standard Deviation). Unit: day*mcg/mL

Measure	Tezepelumab n = 18
Value	974 (320)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Tezepelumab	0 of 18 (0%)	7 of 18 (38.9%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
CSR SynopsisLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Related trials for Asthma

RecruitingPhase 1
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RecruitingPhase 1
A Study to Compare the Relative Potency of Salbutamol Administered Via Metered Dose Inhalers (MDI) Containing Propellants HFA-152a to HFA-134a in Mild Asthmatics Aged 18 to 65 Inclusive
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jonathan Grigg, MD principal investigator

Royal London Hospital, United Kingdom

6 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tezepelumab in people with Asthma, run by AstraZeneca at 6 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United Kingdom, Hungary, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Serum Concentration (Cmax) of Tezepelumab (time frame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04673630.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2024.