Clinical Trial Results:
A phase III/IV randomised open-label study and comparison of the immunogenicity and safety of a single adolescent booster dose of a meningococcal group C conjugate-containing booster vaccine (Meningitec™, or Menjugate™, or NeisVac-C™, or Menitorix™), when given concurrently with an acellular pertussis-containing booster vaccine (Repevax™ or IPV-Boostrix™)
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Summary
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EudraCT number |
2012-005273-31 |
Trial protocol |
GB |
Global end of trial date |
31 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Jan 2019
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First version publication date |
02 Jan 2019
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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 |
HPARSRSG12/06
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02526394 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Public Health England
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Sponsor organisation address |
Wellington House , London , United Kingdom, SE1 8UG
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Public contact |
Dr Elizabeth Coates
, Public Health England, 01980 612922, elizabeth.coates@phe.gov.uk
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Scientific contact |
Dr Elizabeth Coates
, Public Health England, 01980 612922, elizabeth.coates@phe.gov.uk
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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 |
17 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2017
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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 two principal objectives are:
1. IMMUNE RESPONSES TO MENINGITIS C AND WHOOPING COUGH:
To estimate and compare the specific immune responses to concurrently administered booster vaccines against meningitis C and whooping cough in healthy adolescents.
Participants will be adolescents aged 14 to 17 years, who have completed the UK childhood schedule of meningitis C and whooping cough vaccines appropriate for their age. Each participant in the trial will receive two vaccines given concomitantly:
(a) a single dose of ONE of Meningitec™, Menjugate™, NeisVac-C™ , or Menitorix™ (meningitis C vaccines).
(b) EITHER Repevax or IPV-Boostrix (whooping cough containing vaccines).
Thus there will be eight different combinations of meningitis C and whooping cough-containing vaccines (and accordingly, eight arms/groups of study participants)
Blood levels of specific antibodies against meningitis C and whooping cough will be measured in each participant. The measurements will be taken
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Protection of trial subjects |
Fieldwork undertaken by specialist vaccine research nurses trained in paediatric venepuncture techniques. Participants who were consented to provide blood samples were offered local anaesthetic cream prior to venepuncture
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Sep 2013
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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 |
United Kingdom: 388
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Worldwide total number of subjects |
388
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EEA total number of subjects |
388
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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) |
388
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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 |
388 subjects randomised to receive one of two TdaP/IPV booster vaccines with a concomitant MenC containing booster vaccine . Subjects were recruited from general practices in Hertfordshire and Gloucestershire | |||||||||
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Pre-assignment
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Screening details |
Subjects screened to ensure they did not have any of the following conditions : Any contraindications to receipt of the study vaccines and had received appropriate primary immunisation with a pertussis containing vaccine | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
388 | |||||||||
Number of subjects completed |
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Period 1
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Period 1 title |
Period 1 (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ARM1 | |||||||||
Arm description |
Randomised to receive a five component acellular pertussis booster vaccine (Repevax™) (Sanofi). | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Repevax™Sanofi
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.5ml
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Arm title
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ARM2 | |||||||||
Arm description |
Randomised to receive a three component acellular pertussis booster vaccine IPV-Boostrix™) (GSK | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
IPV-Boostrix™) (GSK
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Suspension for injection in pre-filled syringe
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Routes of administration |
Intramuscular use
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Dosage and administration details |
0.5ml
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Baseline characteristics reporting groups
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Reporting group title |
ARM1
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Reporting group description |
Randomised to receive a five component acellular pertussis booster vaccine (Repevax™) (Sanofi). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
ARM2
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Reporting group description |
Randomised to receive a three component acellular pertussis booster vaccine IPV-Boostrix™) (GSK | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ARM1
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Reporting group description |
Randomised to receive a five component acellular pertussis booster vaccine (Repevax™) (Sanofi). | ||
Reporting group title |
ARM2
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Reporting group description |
Randomised to receive a three component acellular pertussis booster vaccine IPV-Boostrix™) (GSK | ||
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End point title |
Primary immunological | |||||||||
End point description |
• Percentage of subjects with serogroup C rSBA titres ≥ 8 at 3 -6 wks after vaccination
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End point type |
Primary
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End point timeframe |
3 to 6 weeks after vaccination
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Statistical analysis title |
Pre planned Analysis | |||||||||
Statistical analysis description |
In brief, a per-protocol analysis will be completed for the immunogenicity data. Proportions with meningococcal serogroup C-specific rSBA titers ≥8 and ≥ 128 as well as GMTs will be calculated with 95% confidence intervals (95% CIs) within each study arm and also aggregating across the dTaP arms (after testing for an interaction at 1% level). Proportions with ≥4-fold rises in SBA from baseline and geometric mean fold rises from baseline will also be calculated with 95% CIs.
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Comparison groups |
ARM1 v ARM2
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Number of subjects included in analysis |
376
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 5 | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Vaccination to last visit for blood sampling at 3-6 weeks post vaccination
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Adverse event reporting additional description |
All SAEs will be reported according to relevant research governance requirements.
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Assessment type |
Non-systematic | |||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
ARM 1
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Reporting group description |
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Reporting group title |
ARM2
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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? Yes | |||
Date |
Amendment |
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07 Jun 2013 |
Changes made as advised by the reviewing Research Ethics Committee, upon issuance of favourable ethical opinion.
- .Participant’s health diary included as an Appendix (Appendix 6)
- Abbreviations in the Participant Information Sheet were expanded to full words (and in all other participant-facing documents: GP covering letters; pre-information leaflets; Assent Form; and Consent Forms).
- Document dates and version numbers updated as appropriate
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19 Jul 2013 |
Removal of Menjugate groups due to lack of product availability – changes throughout the document and appendices |
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07 Aug 2014 |
Addition of Denela 5% anaesthetic cream (Auden Mackenzie Ltd) to those which may be provided for use prior to venepuncture. |
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11 May 2015 |
Addition of Appendix 9 to document changes in response to a national policy change in meningococcal vaccination. |
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24 Nov 2015 |
Change of study title from A phase III/IV randomised open-label study and comparison of the immunogenicity and safety of a single adolescent booster dose of a meningococcal group C conjugate-containing booster vaccine (Meningitec™, OR NeisVac-C™ , OR Menitorix™), when given concurrently with an acellular pertussis-containing booster vaccine (Repevax™ or IPV-Boostrix™)
To
A phase III/IV randomised open-label study and comparison of the immunogenicity and safety of a single adolescent booster dose of a meningococcal booster vaccine (Meningitec™, OR NeisVac-C™ , OR Menitorix™ OR Neminrix™ OR Menveo™), when given concurrently with an acellular pertussis-containing booster vaccine (Repevax™ or IPV-Boostrix™)
PIL and consent forms, and GP information letter – typographical error, Men ACWY is now substituted for MenC, reflecting the vaccine that will be given as previously approved by REC.
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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. | |||
| Numbers recruited less than planned due to changing availability of concomitant meningococcal c containing vaccines . Power calculation redone to ensure adequate numbers in ARM1 and ARM2 given the quadrivalent ACYW vaccine concomitantly | |||
