Clinical Trial Results:
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
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Summary
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EudraCT number |
2020-000554-97 |
Trial protocol |
GB HU |
Global end of trial date |
27 Sep 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Mar 2023
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First version publication date |
28 Mar 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
D5180C00025
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04673630 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
Karlebyhusentren, B674 Astraallen, Södertälje, Sweden, 151 85
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Public contact |
Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
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Scientific contact |
Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001613-PIP01-14 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
27 Sep 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Sep 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the study was to describe the Pharmacokinetic (PK) parameters following a single subcutaneous (SC) administration of tezepelumab in children with mild, moderate, or severe asthma.
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Protection of trial subjects |
This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice, applicable regulatory requirements, and the AstraZeneca policy on Bioethics.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Feb 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 8
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Country: Number of subjects enrolled |
Hungary: 2
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Country: Number of subjects enrolled |
South Africa: 8
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Worldwide total number of subjects |
18
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
18
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This Phase I open-label study was conducted in pediatric participants with mild, moderate, or severe asthma at 6 investigational sites. | ||||||
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Pre-assignment
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Screening details |
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. | ||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Tezepelumab | ||||||
Arm description |
Participants received a single dose of tezepelumab SC injection on Day 1. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Tezepelumab
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Investigational medicinal product code |
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Other name |
MEDI9929, AMG 157
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Single SC injection of tezepelumab administered by a healthcare professional on Day 1.
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Baseline characteristics reporting groups
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Reporting group title |
Tezepelumab
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Reporting group description |
Participants received a single dose of tezepelumab SC injection on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Tezepelumab
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Reporting group description |
Participants received a single dose of tezepelumab SC injection on Day 1. | ||
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End point title |
Maximum Observed Serum Concentration (Cmax) of Tezepelumab [1] | ||||||||
End point description |
Blood samples were collected to determine the Cmax of tezepelumab. The PK parameters were estimated using non-compartmental analysis method. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Achieve Maximum Observed Serum Concentration (tmax) of Tezepelumab [2] | ||||||||
End point description |
Blood samples were collected to determine the tmax of tezepelumab. The PK parameters were estimated using non-compartmental analysis method. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve From Time Zero to The Last Measurable Concentration (AUC0-last) of Tezepelumab [3] | ||||||||
End point description |
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. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Tezepelumab [4] | ||||||||
End point description |
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. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Terminal Phase Elimination Half-Life (t1/2) of Tezepelumab [5] | ||||||||
End point description |
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. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Clearance (CL/F) of Tezepelumab [6] | ||||||||
End point description |
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. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Steady-State Volume of Distribution (Vss/F) of Tezepelumab [7] | ||||||||
End point description |
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. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Volume of Distribution (Vz/F) of Tezepelumab [8] | ||||||||
End point description |
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. 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).
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End point type |
Primary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 3, 7, 11, 15, 29, 57 and 85
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistical analysis was performed for the primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Anti-Drug Antibody (ADA) Response to Tezepelumab | ||||||||||||||||||||||||
End point description |
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. The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
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End point type |
Secondary
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End point timeframe |
Predose and within ± 1 hour of postdose on Day 1; on Days 29 and 85
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From the first dose administration (Day 1) up to study completion (End of Study/Day 85 visit) or withdrawal date
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Adverse event reporting additional description |
The Safety analysis set included all participants who received at least 1 dose of tezepelumab.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Tezepelumab
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Reporting group description |
Participants received a single dose of tezepelumab SC injection on Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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21 Jul 2020 |
Clarified that study start occur only when it is acceptable and safe to do so in accordance with local and national guidelines. Testing for Coronavirus Disease 2019 (COVID-19) and additional visits added. Addition of new exclusion criteria for participants that were positive for COVID-19 and/or had signs and/or symptoms indicative of present or past multisystem inflammatory syndrome. Screening classification for participants with a positive COVID-19 test clarified. Volume of blood clarified for severe acute respiratory syndrome coronavirus 2 serology to allow for testing of COVID 19. Details of mitigations added that could be employed to ensure study continuity in the event of a civil crisis, natural disaster or public health crisis. New section added for COVID-19 safety assessment procedure. New section added for pandemic impact assessment for COVID-19. New requirements for performing spirometry added, including the procedure for participants testing positive for COVID-19, and clarification regarding the safety of performing spirometry. New requirements for conducting the fractional exhaled nitric oxide test added, including the procedure for participants testing positive for COVID 19, and clarification regarding the safety of performing the test. Updated text to clarify that approximately 14 participants will receive a single SC dose of tezepelumab. Additional information added to clarify replacement of participants who did not receive tezepelumab or complete all required evaluations. |
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13 May 2021 |
The COVID-19 viral testing procedure updated to rapid test at local laboratory instead of at central laboratory at Visit 1 and Visit 2. Removed exclusion for use of systemic or intra-articular glucocorticosteroids for conditions other than asthma for 3 months prior to Visit 2 and discouraged until end of study. Change evidence of asthma by removing post-bronchodilator spirometry or historical reversibility criteria and adding to physician diagnosis of asthma as defined by regional guidelines and Investigator review of medical history. Change in participant’s pre-bronchodilator forced expiratory volume in one second criteria from ≥ 70% to ≥ 50% of predicted normal value. Updated to allow more than 1 rescreen attempt per participant, as long as the study physician had deemed the reason for rescreen was valid. |
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06 Jan 2022 |
Removed inclusion criteria for body mass index for age at both screening and Day 1 to include full span of growth percentiles. Updated exclusion criteria around a history of a deterioration in asthma, asthma exacerbation requiring glucocorticoids, and systemic corticosteroid use for the maintenance treatment of asthma to decrease time restriction from 3 months to 6 weeks. Updated exclusion criteria around a history of overnight hospitalisation for asthma from 6 months to 3 months prior to Visit 1, up to and including Visit 2 (Day 1). Updated location where the study was conducted to include approximately 10 study sites globally. Exclusion criteria added relating to COVID-19. Restricted medications updated to allow administration of COVID-19 vaccinations during study conduct. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
