Clinical trial NCT04673630: Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: Mild asthma
Moderate asthma
Severe asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2020-12-17
Enrollment: 18
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
measure: Time to Achieve Maximum Observed Serum Concentration (Tmax) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
measure: Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
measure: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
measure: Terminal Phase Elimination Half-Life (t1/2) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
measure: Apparent Clearance (CL/F) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
measure: Apparent Steady-State Volume of Distribution (Vss/F) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
measure: Apparent Volume of Distribution (Vz/F) of Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
Secondary outcomes:
measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab
timeFrame: Predose and within ± 1 hour of postdose on Day 1; on Days 29 and 85
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Research Site
city: Cape Town
country: South Africa
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Royal London Hospital, United Kingdom
name: Jonathan Grigg, MD
role: PRINCIPAL_INVESTIGATOR
References: