Clinical Trial Results:
The effects of endotoxin challenge on the immune response elicited by a subsequent challenge with Fluenz™ in healthy volunteers, a pilot study
Summary
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EudraCT number |
2015-004023-31 |
Trial protocol |
NL |
Global end of trial date |
26 Feb 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jul 2022
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First version publication date |
08 Jul 2022
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Other versions |
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Summary report(s) |
Development of Endotoxin Tolerance Does Not Influence the Response to a Challenge with the Mucosal Live-Attenuated Influenza Vaccine in Humans In Vivo |
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 |
LPS-Fluenz
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02642237 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Radboud University Nijmegen Medical Centre
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Sponsor organisation address |
Geert Grooteplein 10, Nijmegen, Netherlands, 6500 HB
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Public contact |
Research IC, office of Rebecca Koch, Radboudumc, rebecca.koch@radboudumc.nl
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Scientific contact |
Research IC, office of Rebecca Koch, Radboudumc, rebecca.koch@radboudumc.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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 |
26 Feb 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Feb 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
26 Feb 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 the study is to investigate the effects of an endotoxin challenge and subsequent development of endotoxin tolerance on the local immune response following Fluenz™ administration in vivo. The primary outcome measure is the difference in concentrations of CXCL-10 in nasal wash between subjects in the placebo-Fluenz™ group and the LPS-Fluenz™ group.
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Protection of trial subjects |
All subjects provided written informed consent, all subjects were healthy. Subjects were asked to refrain from caffeine and alcohol intake 24 h, and from food 12 h before the LPS/placebo challenge.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Dec 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 |
Netherlands: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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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) |
0
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Adults (18-64 years) |
30
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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 |
30 healthy, non-smoking male subjects aged 18–35 years gave written informed consent to participate in the study | ||||||||||||||||||
Pre-assignment
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Screening details |
- | ||||||||||||||||||
Pre-assignment period milestones
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Number of subjects started |
30 | ||||||||||||||||||
Number of subjects completed |
30 | ||||||||||||||||||
Period 1
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Period 1 title |
LPS/placebo challenge
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
0.9% saline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Intravenous bolus injection 0.9% saline
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Arm title
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Lipopolysaccharide (LPS) | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Lipopolysaccharide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Intravenous bolus administration of LPS (2 ng/kg)
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Period 2
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Period 2 title |
Viral challenge
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo+Fluenz | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
0.9% saline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Intravesical solution/solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Intravenous bolus injection 0.9% saline
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Investigational medicinal product name |
Live-attenuated quadrivalent influenza vaccine (LAIV) Fluenz Tetra
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
Intranasal vaccination with the live-attenuated quadrivalent influenza vaccine (LAIV) Fluenz Tetra (0.1 ml/nostril). Subjects remained in the recumbent position for 1 min after Fluenz administration.
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Arm title
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LPS+Fluenz | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Lipopolysaccharide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
Intravenous bolus administration of LPS (2 ng/kg)
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Investigational medicinal product name |
Live-attenuated quadrivalent influenza vaccine (LAIV) Fluenz Tetra
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Nasal spray, solution
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Routes of administration |
Intranasal use
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Dosage and administration details |
Intranasal vaccination with the live-attenuated quadrivalent influenza vaccine (LAIV) Fluenz Tetra (0.1 ml/nostril). Subjects remained in the recumbent position for 1 min after Fluenz administration.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lipopolysaccharide (LPS)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
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Reporting group title |
Lipopolysaccharide (LPS)
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Reporting group description |
- | ||
Reporting group title |
Placebo+Fluenz
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Reporting group description |
- | ||
Reporting group title |
LPS+Fluenz
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Reporting group description |
- |
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End point title |
Viral load, Influenza A | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Subjects were challenged with LPS/Placebo on day 0, tested if viral load was present at day 7. Measurements of viral load on day 8
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Statistical analysis title |
Comparison | |||||||||||||||
Comparison groups |
Placebo+Fluenz v LPS+Fluenz
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||
P-value |
= 0.54 | |||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||
Confidence interval |
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End point title |
Viral load, Influenza B | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Subjects were challenged with LPS/Placebo on day 0, tested if viral load was present at day 7. Measurements of viral load on day 8
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Statistical analysis title |
Comparison | |||||||||||||||
Comparison groups |
Placebo+Fluenz v LPS+Fluenz
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||
P-value |
= 0.45 | |||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||
Confidence interval |
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End point title |
IgG seroconversion, A/H1N1 | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Subjects were challenged with LPS/Placebo on day 0 and displayed infectivity after inoculation with Fluenz on day 7. Seroconverted subjects were counted on day 35.
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No statistical analyses for this end point |
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End point title |
IgG seroconversion, A/H3N2 | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Subjects were challenged with LPS/Placebo on day 0 and displayed infectivity after inoculation with Fluenz on day 7. Seroconverted subjects were counted on day 35.
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No statistical analyses for this end point |
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End point title |
IgG seroconversion, B/Phuket | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Subjects were challenged with LPS/Placebo on day 0 and displayed infectivity after inoculation with Fluenz on day 7. Seroconverted subjects were counted on day 35.
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No statistical analyses for this end point |
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End point title |
IgG seroconversion, B/Brisbane | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Subjects were challenged with LPS/Placebo on day 0 and displayed infectivity after inoculation with Fluenz on day 7. Seroconverted subjects were counted on day 35.
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No statistical analyses for this end point |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Throughout complete study
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Assessment type |
Non-systematic | |||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
CTCAE guidelines | |||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
- | |||||||||||||||
Reporting group title |
Lipopolysaccharide (LPS)
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Reporting group description |
- | |||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||
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Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No non-serious adverse events were recorded. |
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
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. | |||
Study was performed during winter season (possible viral co-infections) | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/29312282 |