Clinical Trial Results:
The effects of BCG-vaccination on the immune response induced by influenza-vaccination in healthy volunteers
A pilot proof-of-principle study
Summary
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EudraCT number |
2014-000966-23 |
Trial protocol |
NL |
Global end of trial date |
31 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
26 May 2021
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First version publication date |
26 May 2021
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Other versions |
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Summary report(s) |
BCG Vaccination Enhances the Immunogenicity of Subsequent Influenza Vaccination in Healthy Volunteers: A Randomized, Placebo-Controlled Pilot Study |
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_influenza
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
clinical trials.gov: volgt | ||
Sponsors
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Sponsor organisation name |
Radboud University Nijmegen Medical Centre
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Sponsor organisation address |
Geert Grooteplein Zuid 10, Nijmegen, Netherlands, 6525 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 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 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 |
To determine the effects of BCG-vaccination on the immune response induced by subsequent influenza vaccination in healthy volunteers. This will be determined by measuring the Th1/Th2 response, and antibody titers induced by influenza vaccination in seronegative healthy volunteers who are, prior to influenza vaccination, vaccinated with either BCG or placebo in a double-blind randomized manner.
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Protection of trial subjects |
Physical examination prior to start of experiment. Informed consent required.
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Background therapy |
intramuscular injection of 0.5 mL of trivalent 2013–2014 seasonal influenza vaccine containing A/California/7/2009 (A[H1N1]pdm09)–derived strain, Victoria/361/2011-related strain derived from A/Texas/50/2012 (A[H3N2]2012), and B/Massachusets/2/2012 (B/2012)–derived strain surface antigens and no adjuvants (Batrevac; Abbot Biologicals, Weesp, the Netherlands) | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2014
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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 |
Netherlands: 40
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Worldwide total number of subjects |
40
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EEA total number of subjects |
40
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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) |
40
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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 |
healthy, nonsmoking | |||||||||
Pre-assignment
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Screening details |
Subjects who received BCG vaccine before, received influenza vaccination in the previous year, or had febrile illness during the 2 weeks before the experiment were excluded. Subjects were not allowed to use prescription drugs. | |||||||||
Period 1
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Period 1 title |
BCG vaccine/placebo (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 |
Investigator, Subject | |||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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BCG vaccine and infuenza | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Bacille Calmette Guérin vaccination
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Investigational medicinal product code |
RVG 17661
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Other name |
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
0.1 mL of live attenuated BCG vaccine (BCG vaccine SSI/Danish strain 1331; Bilthoven Biologicals, Bilthoven, the Netherlands)
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Investigational medicinal product name |
influenza vaccin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
intramuscular
injection of 0.5 mL of trivalent 2013–2014 seasonal
influenza vaccine containing A/California/7/2009 (A[H1N1]
pdm09)–derived strain, Victoria/361/2011-related strain derived
from A/Texas/50/2012 (A[H3N2]2012), and B/Massachusets/
2/2012 (B/2012)–derived strain surface antigens and no
adjuvants (Batrevac; Abbot Biologicals, Weesp, the Netherlands)
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Arm title
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Placebo and influenza | |||||||||
Arm description |
- | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
NaCl
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
0.1 mL NaCl 0.9%
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Investigational medicinal product name |
influenza vaccin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
intramuscular
injection of 0.5 mL of trivalent 2013–2014 seasonal
influenza vaccine containing A/California/7/2009 (A[H1N1]
pdm09)–derived strain, Victoria/361/2011-related strain derived
from A/Texas/50/2012 (A[H3N2]2012), and B/Massachusets/
2/2012 (B/2012)–derived strain surface antigens and no
adjuvants (Batrevac; Abbot Biologicals, Weesp, the Netherlands)
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Baseline characteristics reporting groups
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Reporting group title |
BCG vaccine and infuenza
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo and influenza
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
BCG
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
BCG group
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Subject analysis set title |
PLacebo
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Placebo group
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End points reporting groups
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Reporting group title |
BCG vaccine and infuenza
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Reporting group description |
- | ||
Reporting group title |
Placebo and influenza
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Reporting group description |
- | ||
Subject analysis set title |
BCG
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
BCG group
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Subject analysis set title |
PLacebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Placebo group
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End point title |
Difference in HI antibody titers | |||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
between day 0 and 28
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Attachments |
raw data HAI assays HAI + GMT uitgewerkt |
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Statistical analysis title |
A(H1N1) titer increase | |||||||||||||||||||||||||||||||||||||||
Comparison groups |
BCG vaccine and infuenza v Placebo and influenza
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Number of subjects included in analysis |
40
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 | |||||||||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||||||||||||||||||||||||||
Parameter type |
2-fold change | |||||||||||||||||||||||||||||||||||||||
Confidence interval |
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level |
95% | |||||||||||||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.025 | |||||||||||||||||||||||||||||||||||||||
upper limit |
0.025 | |||||||||||||||||||||||||||||||||||||||
Variability estimate |
Standard deviation
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Adverse events information
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Timeframe for reporting adverse events |
day 0 till 28
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
BCG vaccine and infuenza
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo and influenza
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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. | |||
relatively small sample size, humoral immunity is not the only mechanism involved in the protection against influenza virus infection. It is not clear what the optimal timing of the BCG vaccinations in context of influenza is. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/26071565 |