Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma (TRAILHEAD)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: Tezepelumab

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1094
    • Research Site
• South Africa
  • Cape Town, South Africa, 7700
    • Research Site
• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
    • Research Site
  • Glasgow, United Kingdom, G51 4TF
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • London, United Kingdom, E1 1BB
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 9 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tezepelumab; Tezepelumab subcutaneous injection	Biological: Tezepelumab; Single dose subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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.	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.	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.	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.	Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Amgen
• Investigators: Principal Investigator: Jonathan Grigg, MD, Royal London Hospital, United Kingdom

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): September 27, 2022
• Study Completion (Actual): September 27, 2022

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Mild asthma; Moderate asthma; Severe asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D5180C00025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No