Trial Outcomes & Findings for Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma (NCT NCT04673630)

NCT ID: NCT04673630

Last Updated: 2024-01-08

Results Overview

Blood samples were collected to determine the Cmax of tezepelumab. The Pharmacokinetic (PK) parameters were estimated using non-compartmental analysis method.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 18 participants
• Primary outcome timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
• Results posted on: 2024-01-08

Participant Flow

This Phase I open-label study was conducted in pediatric participants with mild, moderate, or severe asthma at 6 investigational sites in the UK, Hungary, and South Africa between 23 February 2021 and 27 September 2022.

This study consists a screening period (14 days), and a single dose treatment (Day 1) and follow-up period (85 days). A total of 18 participants were treated in the study.

Participant milestones

Measure	Tezepelumab Participants received a single dose of tezepelumab subcutaneous (SC) injection on Day 1.
Overall Study STARTED	18
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the Pharmacokinetics of Tezepelumab in Children With Asthma

Baseline characteristics by cohort

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Age, Continuous	7.9 years STANDARD_DEVIATION 1.78 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants
Race/Ethnicity, Customized Other	9 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

Blood samples were collected to determine the Cmax of tezepelumab. The Pharmacokinetic (PK) parameters were estimated using non-compartmental analysis method.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Maximum Observed Serum Concentration (Cmax) of Tezepelumab	27.1 microgram per milliliter (mcg/mL) Standard Deviation 11.9

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

Blood samples were collected to determine the tmax of tezepelumab. The PK parameters were estimated using non-compartmental analysis method.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Time to Achieve Maximum Observed Serum Concentration (Tmax) of Tezepelumab	3.47 day Interval 1.92 to 9.96

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

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.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab	872 day*mcg/mL Standard Deviation 285

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

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.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tezepelumab	974 day*mcg/mL Standard Deviation 320

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

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.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Terminal Phase Elimination Half-Life (t1/2) of Tezepelumab	25.7 day Standard Deviation 5.94

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

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.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Apparent Clearance (CL/F) of Tezepelumab	0.0802 liter per day Standard Deviation 0.0295

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

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.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Apparent Steady-State Volume of Distribution (Vss/F) of Tezepelumab	3.08 liter Standard Deviation 1.32

PRIMARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85

Population: 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).

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.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Apparent Volume of Distribution (Vz/F) of Tezepelumab	2.98 liter Standard Deviation 1.26

SECONDARY outcome

Timeframe: Predose and within ± 1 hour of postdose on Day 1; on Days 29 and 85

Population: The Safety analysis set included all participants who received at least 1 dose of 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.

Outcome measures

Measure	Tezepelumab n=18 Participants Participants received a single dose of tezepelumab SC injection on Day 1.
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Baseline and at least 1 post-baseline ADA positive	1 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Baseline ADA positive regardless of post-baseline	3 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Any post-baseline ADA positive	1 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab ADA prevalence	3 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Only baseline ADA positive	2 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Treatment-induced ADA positive	0 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Treatment-boosted ADA positive	0 Participants
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab Treatment-emergent ADA positive	0 Participants

Adverse Events

Tezepelumab

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Tezepelumab n=18 participants at risk Participants received a single dose of tezepelumab SC injection on Day 1.
Infections and infestations COVID-19	11.1% 2/18 • Number of events 2 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Infections and infestations Nasopharyngitis	11.1% 2/18 • Number of events 2 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Infections and infestations Viral upper respiratory tract infection	5.6% 1/18 • Number of events 1 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Nervous system disorders Headache	11.1% 2/18 • Number of events 2 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Respiratory, thoracic and mediastinal disorders Asthma	5.6% 1/18 • Number of events 1 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 1/18 • Number of events 1 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Gastrointestinal disorders Vomiting	5.6% 1/18 • Number of events 1 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
General disorders Pyrexia	5.6% 1/18 • Number of events 1 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Immune system disorders Seasonal allergy	5.6% 1/18 • Number of events 1 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Injury, poisoning and procedural complications Contusion	5.6% 1/18 • Number of events 2 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Injury, poisoning and procedural complications Fall	5.6% 1/18 • Number of events 2 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • Number of events 1 • From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date The Safety analysis set included all participants who received at least 1 dose of tezepelumab.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place