Clinical Trial Results:
A Single Arm, Open-label Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of Cefiderocol in Hospitalized Paediatric Subjects 3 Months to < 18 Years of Age with Suspected or Confirmed Aerobic Gram-negative Bacterial Infections
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Summary
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EudraCT number |
2019-002120-32 |
Trial protocol |
HU BE LV |
Global end of trial date |
06 Feb 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Dec 2023
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First version publication date |
02 Dec 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 |
1802R2135
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04335539 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Shionogi B.V.
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Sponsor organisation address |
Kingsfordweg 151, Amsterdam, Netherlands, 1043 GR
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Public contact |
Corporate Communications Department, Shionogi & Co., Ltd, +81 662097885, shionogiclintrials-admin@shionogi.co.jp
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Scientific contact |
Corporate Communications Department, Shionogi & Co., Ltd, +81 662097885, shionogiclintrials-admin@shionogi.co.jp
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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-002133-PIP01-17 | ||
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 |
25 Jul 2023
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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 |
06 Feb 2023
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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 |
• To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized paediatric subjects 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the pharmacokinetics (PK) of cefiderocol after single-dose administration of cefiderocol in hospitalized paediatric subjects 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the safety and tolerability of cefiderocol after multiple-dose administration in hospitalized paediatric subjects 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
• To assess the PK of cefiderocol after multiple-dose administration in hospitalized paediatric subjects 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections
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Protection of trial subjects |
Reviewing interim aggregate study data, individual case narratives and assessing the benefit/risk through examination of the safety of study treatments.
Advising the Company on whether the current internal assessment and approach is scientifically sound or any change should be considered (especially in the
interest of patient safety).
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Background therapy |
Various standard of care therapies are permitted | ||
Evidence for comparator |
N/A | ||
Actual start date of recruitment |
18 Aug 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Spain: 1
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Country: Number of subjects enrolled |
Belgium: 5
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Country: Number of subjects enrolled |
Estonia: 4
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Country: Number of subjects enrolled |
Latvia: 1
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Country: Number of subjects enrolled |
Ukraine: 14
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Country: Number of subjects enrolled |
Thailand: 8
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Country: Number of subjects enrolled |
Georgia: 20
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Worldwide total number of subjects |
53
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EEA total number of subjects |
11
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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) |
12
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Children (2-11 years) |
34
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Adolescents (12-17 years) |
7
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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 |
The single-dose phase in all 4 cohorts confirmed cefiderocol exposures in at least 6 subjects prior to conducting a multiple-dose phase (Cohorts 2, 3, and 4) in additional subjects. Enrollment was stopped for the applicable cohort to allow for analysis of the PK data prior to moving from single-dose to multiple-dose in Cohorts 2, 3, and 4. | ||||||||||
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Pre-assignment
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Screening details |
Screening occurred within 4 days prior to Treatment Day 1 or on Treatment Day 1 in both the single- and multiple-dose phase. Prior to Screening, sites were asked to send a Permission to Screen Form containing limited information of the potential subject to Shionogi medical monitors for evaluation and agreement. | ||||||||||
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Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
Open label study
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Arms
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Arm title
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study | ||||||||||
Arm description |
All patients entered the study in a single arm | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Cefiderocol
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Investigational medicinal product code |
S-649266
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
The dose of cefiderocol for the Single-dose Phase was determined based on body weight only; the maximum dose to be administered was not to exceed 2000 mg.
Cefiderocol was administered as an intravenous (IV) infusion over 3 hours (in addition to SOC) at any time during the SOC treatment regimen.
The dose for the Multiple-dose Phase was determined based on both body weight and renal function; the maximum dose to be administered did not exceed 2000 mg. In the Multiple-dose Phase, cefiderocol was administered on Day 1 (in addition to SOC), within 72 hours of the start of potentially effective treatment with SOC antibiotics for infection. Participants subsequently received cefiderocol every 8 hours (q8h) as an IV infusion over 3 hours for an expected 5 to 14 days.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial (overall period)
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
study
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Reporting group description |
All patients entered the study in a single arm | ||
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End point title |
To assess the safety and tolerability of cefiderocol after single-dose administration in hospitalized pediatric participants 3 months to < 18 years of age with suspected or confirmed aerobic Gramnegative bacterial infections [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
From screening to end of study
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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: There was no comparison in this study |
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| No statistical analyses for this end point | |||||||
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End point title |
To assess the safety and tolerability of cefiderocol after multiple-dose administration in hospitalized pediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gramnegative bacterial infections [2] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
From screening to end of study
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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: There was no comparison in this study |
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| No statistical analyses for this end point | |||||||
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End point title |
To assess the PK of cefiderocol after single dose administration of cefiderocol in hospitalized pediatric participants 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections [3] | ||||||||
End point description |
The geometric mean concentrations and geometric SD at 3 hours after the start of infusion for the single-dose cohort across the 4 cohorts
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End point type |
Primary
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End point timeframe |
From screening to end of study
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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: There was no comparison in this study |
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| No statistical analyses for this end point | |||||||||
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End point title |
To assess the PK of cefiderocol after single dose administration of cefiderocol in hospitalized pediatric participants 3 months to < 18 years of age with suspected or confirmed aerobic Gram-negative bacterial infections [4] | ||||||||
End point description |
The geometric mean concentrations and geometric SD at 8 hours after the start of infusion for the single-dose cohort across the 4 cohorts
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End point type |
Primary
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End point timeframe |
From screening to end of study
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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: There was no comparison in this study |
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| No statistical analyses for this end point | |||||||||
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End point title |
To assess the PK of cefiderocol after multiple-dose administration in hospitalized pediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections [5] | ||||||||
End point description |
The geometric mean concentrations and geometric SD at 3 hours of Day3 & Day 4 after the start of infusion for the multiple-dose cohort across the 4 cohorts
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End point type |
Primary
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End point timeframe |
From screening to end of study
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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: There was no comparison in this study |
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| No statistical analyses for this end point | |||||||||
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End point title |
To assess the PK of cefiderocol after multiple-dose administration in hospitalized pediatric participants 3 months to < 12 years of age with suspected or confirmed aerobic Gram-negative bacterial infections [6] | ||||||||
End point description |
The geometric mean concentrations and geometric SD at 8 hours of Day 3 & Day 4 after the start of infusion (before the next infusion in the multiple-dose phase) for the multiple-dose cohort across the 4 cohorts
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End point type |
Primary
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End point timeframe |
From screening to end of study
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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: There was no comparison in this study |
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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 screening to end of study
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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 |
23
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Reporting groups
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Reporting group title |
All subjects
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Reporting group description |
All subjects enrolled and receiving administration of study drug | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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10 Jul 2019 |
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11 Oct 2019 |
2 |
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28 Apr 2020 |
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19 Jan 2021 |
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04 Mar 2021 |
5 |
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18 Nov 2021 |
6 |
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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 | |||
