Clinical Trial Results:
The effects of BCG-vaccination on the innate immune response and immunoparalysis in healthy volunteers
Summary
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EudraCT number |
2013-005520-42 |
Trial protocol |
NL |
Global end of trial date |
31 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jan 2021
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First version publication date |
28 Jan 2021
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Other versions |
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Summary report(s) |
Gamma-Irradiated Bacille Calmette-Guérin Vaccination Does Not Modulate the Innate Immune Response during Experimental Human Endotoxemia in Adult Males |
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 |
BCG-LPS
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
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 |
Jenneke Leentjens, Radboud University Nijmegen Medical Centre, 0031 243668420, jenneke.leentjens@radboudumc.nl
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Scientific contact |
Jenneke Leentjens, Radboud University Nijmegen Medical Centre, 0031 243668420, jenneke.leentjens@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 |
31 Oct 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Oct 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Oct 2014
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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 |
1. Single endotoxemia
To determine the effects of γ-irradiated BCG-vaccination on the in vivo innate immune responses induced by human endotoxemia. This will be determined by measuring plasma levels of various pro- and anti-inflammatory cytokines and assessing the difference in the Lipopolysacharide (LPS)-induced cytokine response between γ-irradiated BCG-vaccined subjects and placebo-treated control subjects.
2. Repeated endotoxemia
To determine the effects of γ-irradiated BCG-vaccination on endotoxin tolerance induced by human endotoxemia. This will be determined by measuring plasma levels of various pro- and anti-inflammatory cytokines and assessing the difference in the LPS-induced cytokine response following the first and second endotoxemia, between γ-irradiated BCG-vaccined and placebo-treated control subjects.
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Protection of trial subjects |
Volunteers gave written informed consent to participate in this study. Throughout the study period, subjects were not allowed to take any drugs, including cetaminophen, and were asked to refrain from alcohol and caffeine 24 hours and from food 12 hours before the start of the endotoxemia experiment. All study procedures were conducted in accordance with the declaration of Helsinki including current revisions and Good Clinical Practice guidelines.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Mar 2014
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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: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
20
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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 |
20 healthy nonsmoking male volunteers gave written informed consent to participate in this study. | |||||||||
Pre-assignment
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Screening details |
Subjects were screened before the start of the experiment and had a normal physical examination, electrocardiography, and routine laboratory values. | |||||||||
Period 1
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Period 1 title |
In study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Carer | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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BCG vaccination | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
γ-Irradiated BCG vaccine
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Investigational medicinal product code |
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Other name |
γ-Irradiated BCG vaccine (BCG-Vaccin SSI [Nederlands Vaccin Instituut]) Danish strain 1331
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Pharmaceutical forms |
Concentrate for suspension for injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
Subjects received 0.075 mg (0.1mL) gamma-irradiated BCG vaccine intracutaneously (BCG vaccine SSI; Statens Serum Institut, gamma-irradiation (25–30 kGy) performed by Synergy Health Ede, Netherlands
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Arm title
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Placebo | |||||||||
Arm description |
- | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
BCG-reconstitution fluid: diluted Sauton 1+3; Statens Serum Institut
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
Subjects received 0.1mL placebo intracutaneously
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Baseline characteristics reporting groups
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Reporting group title |
BCG vaccination
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BCG vaccination
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
- |
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End point title |
TNF-alpha | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Area under the curve after LPS injection (until day 10 after injection)
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Statistical analysis title |
TNF-alpha, BCG vs. placebo | ||||||||||||
Comparison groups |
BCG vaccination v Placebo
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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End point title |
IL-6 | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Area under the curve after LPS injection (until day 10 after injection)
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Statistical analysis title |
IL-6, BCG vs. placebo | ||||||||||||
Comparison groups |
BCG vaccination v Placebo
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
After vaccination
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Assessment type |
Systematic | |||||||||||||||||||||
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 |
BCG vaccination
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Reporting group description |
- | |||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | |||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||
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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. | |||
1) Inactivation of the vaccine 2) Timing of interventions 3) Only male 4) Training effects of BCG nullified by LPS 5) Human endotoxemia model is mild 6) No pre-screening of subjects for previous exposure to Mycobacterium tuberculosis | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/25883989 |