Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma

Asthma Clinical Trial

— TRAILHEAD  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04673630
• Other study ID #: D5180C00025
• Status: Completed
• Phase: Phase 1
• Start date: February 23, 2021
• Est. completion date: September 27, 2022

Study information

• Verified date: March 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: September 27, 2022
• Est. primary completion date: September 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 11 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Tezepelumab
Single dose subcutaneous injection

Locations

Country	Name	City	State
Hungary	Research Site	Budapest
South Africa	Research Site	Cape Town
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	London
United Kingdom	Research Site	London

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Amgen

Countries where clinical trial is conducted

Hungary,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Primary	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.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Primary	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.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Primary	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.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Primary	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)/?Z, where ?Z is the first-order rate constant associated with the terminal (log-linear) elimination phase. The PK parameters were estimated using non-compartmental analysis method.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Primary	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.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Primary	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/ ?Z. The PK parameters were estimated using non-compartmental analysis method.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Secondary	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.	Predose and within ± 1 hour of postdose on Day 1; on Days 29 and 85

External Links

•   CSR Synopsis