Clinical Trial Results:
A Phase 1, Open-label Study to Evaluate the Pharmacokinetics of MEDI9929 in Adolescents with Mild to Moderate Asthma
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Summary
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EudraCT number |
2014-005450-19 |
Trial protocol |
PL |
Global end of trial date |
02 May 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jan 2017
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First version publication date |
20 Jan 2017
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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 |
D5180C00002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02512900 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
MedImmune, LLC
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Sponsor organisation address |
One MedImmune Way, Gaithersburg, United States,
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Public contact |
Rene van der Merwe, Senior Director, Clinical Development, Respiratory, and Inflammation, MedImmune, LLC, 011 3013980000 x, information.center@astrazeneca.com
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Scientific contact |
Rene van der Merwe, Senior Director, Clinical Development, Respiratory, and Inflammation, MedImmune, LLC, 011 3013980000 x, 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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 May 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 May 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
02 May 2016
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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 primary objective of this study was to evaluate the PK profile of a single-dose administration of MEDI9929 in adolescent subjects with mild to moderate asthma
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Protection of trial subjects |
The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
Participants in this study continued to receive asthma controller medications consistent with those described at Step 2 to Step 4 of GINA guidelines (GINA, 2014) as prescribed by their physician. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2015
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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 |
Poland: 21
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Worldwide total number of subjects |
21
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EEA total number of subjects |
21
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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) |
0
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Adolescents (12-17 years) |
21
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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 |
Adolescent participants (12 to 17 years, inclusive) with mild to moderate asthma were recruited in an open-label fashion to receive a single-dose of MEDI9929 (also known as tezepelumab or AMG 157) at two study centers in Poland from Sep 2015 to May 2016. | |||||||||
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Pre-assignment
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Screening details |
A total of 26 participants were screened in this study. Of which 21 participants completed the study. Additional 5 participants signed the informed consent but were not enrolled in the study as they were screen failures. The reason for screen failures were not meeting the inclusion/exclusion criteria, lost to follow-up, and/or consent withdrawal. | |||||||||
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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 | |||||||||
Blinding implementation details |
This is an Open-label study
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1 | |||||||||
Arm description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
MEDI9929
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Single-dose subcutaneous
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Arm title
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Cohort 2 | |||||||||
Arm description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
MEDI9929
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Single-dose subcutaneous
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Baseline characteristics reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2
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Reporting group description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
MEDI9929
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to participants, aged 12 to 17 years, inclusive.
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End points reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | ||
Reporting group title |
Cohort 2
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Reporting group description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | ||
Subject analysis set title |
MEDI9929
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to participants, aged 12 to 17 years, inclusive.
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End point title |
Area Under the Concentration-time Curve From Zero to Infinity (AUC [0-infinity]) [1] | ||||||||||||
End point description |
The pharmacokinetic (PK) parameter AUC (0 to infinity) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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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 Zero to Last Observation (AUC [0-t]) [2] | ||||||||||||
End point description |
The PK parameter AUC (0-t) was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Dose-normalized AUC (0-infinity) (AUC [0 infinity]/D) [3] | ||||||||||||
End point description |
The AUC (0-infinity)/D is the area under concentration-time curve extrapolated to infinity postdose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Maximum Observed Serum Concentration (Cmax) [4] | ||||||||||||
End point description |
The PK parameter Cmax was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Dose-normalized Cmax (Cmax/D) [5] | ||||||||||||
End point description |
The Cmax/D is the maximum observed concentration post dose normalized by MEDI9929 dose. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Time to Reach Cmax (Tmax) [6] | ||||||||||||
End point description |
The Tmax is the time to maximum observed serum concentration of MEDI9929. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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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,z) [7] | ||||||||||||
End point description |
The t½,z is the time measured for the serum drug concentration of MEDI9929 to decrease by one half. The PK parameter was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Apparent Clearance (CL/F) [8] | ||||||||||||
End point description |
The PK parameter CL/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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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) [9] | ||||||||||||
End point description |
The PK parameter Vss/F was estimated based on the serum concentrations of MEDI9929. Serum concentrations of MEDI9929 were measured by enzyme-linked immunosorbent assay.
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End point type |
Primary
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End point timeframe |
Day 1 (predose) and postdose.
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| Notes [9] - 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: Statistical analysis was not applicable since there was no formal statistical testing or modeling performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events | |||||||||||||||
End point description |
An adverse event (AE) is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) is any AE resulting in any of the following outcomes such as death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly or birth defect, or is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above. A TEAE is defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0
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End point type |
Secondary
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End point timeframe |
From the start of study drug administration up to end of follow-up period
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Treatment-emergent Adverse Events Related to Vital Sign Parameters and Physical Findings | |||||||||
End point description |
Vital signs (blood pressure, temperature, pulse, and respiratory rate) were performed throughout the study. The TEAEs related to vital signs in participants were reported.
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End point type |
Secondary
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End point timeframe |
From the start of study drug administration up to end of follow-up period
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| No statistical analyses for this end point | ||||||||||
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End point title |
Treatment-emergent Adverse Events Related to Laboratory Parameters | |||||||||
End point description |
Laboratory evaluations of blood and urine samples were performed, including hematology (white blood cell count with differential, red blood cell count, hematocrit, hemoglobin and platelet count); serum chemistry: calcium, chloride, potassium, sodium, bicarbonate, aspartate transaminase, alanine transaminase, albumin, uric acid, creatinine, total bilirubin, glucose, alkaline phosphatase, blood urea nitrogen, total protein, and gamma glutamyl transferase; and urinalysis (nitrites, protein, glucose, ketones, urine drug screen, blood, and bilirubin). Number of participants with TEAEs related to laboratory evaluations were reported.
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End point type |
Secondary
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End point timeframe |
From the start of study drug administration up to end of follow-up period
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| No statistical analyses for this end point | ||||||||||
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End point title |
Treatment-emergent Adverse Events Related to Electrocardiogram Evaluations | |||||||||
End point description |
Computerized triplicate 12-lead ECGs as well as Qualitative 12-lead ECGs were obtained during the study. ECG parameters included heart rate, PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with TEAEs related to ECG after the start of study drug were to be reported.
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End point type |
Secondary
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End point timeframe |
From the start of study drug administration up to end of followup period
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| No statistical analyses for this end point | ||||||||||
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End point title |
Number of Participants Positive for Anti-drug Antibodies and With Neutralizing Antibodies for MEDI9929 at any Visit | ||||||||||||||
End point description |
Blood samples for immunogenicity assessment included the determination of anti-drug antibodies (ADA) for MEDI9929. The incidence rate of positive serum antibodies to MEDI9929 were presented. Neutralizing antibody was tested only for the positive ADA samples. Combined immunogenicity data are presented for Cohort 1 and Cohort 2, i.e., for all participants.
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End point type |
Secondary
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End point timeframe |
Day 1 (predose), and postdose.
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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 start of study drug administration up to end of followup period.
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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 |
19.0
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Reporting groups
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Reporting group title |
Cohort 1
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Reporting group description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2
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Reporting group description |
On Day 1, a single dose of MEDI9929 was administered subcutaneously to all participants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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29 Jun 2015 |
Protocol Amendment 1: The major changes were made in response to feedback from the Polish regulatory authorities Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products regarding the period of contraception following administration of investigational product. Minor editing and correction of typographical errors were also addressed. |
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10 Feb 2016 |
Protocol Amendment 2: The purpose of this amendment was to change the Medical Monitor of the study. |
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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 | |||
