Clinical Trial Results:
Assessment of post booster antibody responses in UK infants given a reduced priming schedule of meningococcal serogroup B and 13 valent pneumococcal conjugate vaccines
Summary
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EudraCT number |
2015-000817-32 |
Trial protocol |
GB |
Global end of trial date |
01 Jun 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Feb 2022
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First version publication date |
11 Feb 2022
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Other versions |
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 |
2015/03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02482636 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University of Oxford, Clinical Trials and Research Governance (CTRG)
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Sponsor organisation address |
Boundary Brook House, Oxford, United Kingdom, OX3 7GB
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Public contact |
Oxford Vaccine Group, University of Oxford, 44 1865611400, info@ovg.ox.ac.uk
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Scientific contact |
Oxford Vaccine Group, University of Oxford, 44 1865611400, info@ovg.ox.ac.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 |
26 Oct 2018
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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 |
01 Jun 2021
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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 |
Technical - To assess geometric mean concentrations (GMC) of serotype specific pneumococcal antibody responses measured in the blood sample taken after the final infant vaccinations, usually at 13 months of age, following two or three doses of 13 valent pneumococcal conjugate vaccine (PCV13) at 3 and 12 months or at 2, 4, and 12 months of age
Lay - To assess how much antibody can be detected in the blood sample taken a month after the final infant vaccinations, usually taken at 13 months of age, after two or three doses of the routinely used pneumococcal vaccine, called Prevenar13.
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Protection of trial subjects |
The blood sampling may be uncomfortable but the clinical study staff are very experienced at drawing blood samples and not more than two attempts will be made. Finger or heel (in infants) prick may be attempted if venepuncture proves difficult.
For infants under 3 months of age, oral sucrose solution (such as Sweet-Ease®) may be offered to minimise discomfort (subject to local practice/preference). The parents will be asked if she/he wishes to feed the infant during the procedure to minimise discomfort. An anaesthetic cream (such as EMLA®, Denela or Ametop®), cryogenic spray may be offered for infants one month or older. As per JCVI recommendation, parents will be advised to give their baby three doses of paracetamol (infant formula) prophylactically in the 24 hours after each primary MenB vaccination.
Any stress and discomfort is also reduced by using distraction techniques.
Every effort will be made to protect the participants’ identity. The study will comply with the Data Protection Act, which requires data to be anonymised as soon as it is practical to do so.
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Background therapy |
All participants receive: Bexsero (MenB) at 2, 4 and 12 months of age Infanrix/IPV/Hib at 2,3 and 4 month MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix Rotarix orally at 2 and 3 months Infants may receive one of 2 licensed MMR vaccines depending on local availability and parental consent: Priorix or MMR®II (live attenuated vaccines that protects against measles, mumps and rubella) at 13 months Infant doses of paracetamol are also provided to families to give following the MenB vaccinations at 2 and 4 months of age. | ||
Evidence for comparator |
The Department of Heath JCVI has recommended that the Bexsero vaccine, designed to protect against meningococcal B and other serogroups not covered by the MenC conjugate vaccine, may be cost effective if given as a 2+1 schedule and if the current MenC conjugate vaccine dose given at 3 months is removed. There are no published immunogenicity data for Bexsero when given at 2, 4 and 12 months (the ages at which a 2+1 schedule would be implemented in the UK) and with concomitant Infanrix/IPV/Hib. The MenC conjugate vaccine currently given for primary immunisation at 3 months of age is a tetanus based conjugate which was shown to enhance the response to the Hib component of Infanrix/IPV/Hib. Removal of MenC conjugate vaccine from the infant schedule would raise uncertainty as to the adequacy of the Hib response to Infanrix/IPV/Hib. Another uncertainty about the 2+1 Bexsero schedule is that it would be given at the same appointments currently used for PCV13 (13 valent pneumococcal conjugate vaccine), thus necessitating 3 injections at the first and third infant visits and just one injection at the second. Past experience has shown that there is reluctance among parents, and some health professionals, to give 3 injections at one visit to a very young infant. An option is to reduce PCV13 to a 1+1 schedule, giving a single priming dose at 3 months. Though the immunogenicity of one dose in infancy will be lower than two doses, a prior study with PCV9 showed higher booster responses with fewer priming doses. With the rapidly reducing incidence of PCV13 disease in young children in the UK, and highly effective herd protection, the potentially increased risk of an invasive pneumococcal infection between 4 and 12 months in a child who has only received one dose of PCV13 instead of two will be very low and unlikely to outweigh the cost savings from reducing the number of PCV13 doses from 3 to 2. This study includes two arms defined by their PCV13 schedule as 1+1 or 2+1. | ||
Actual start date of recruitment |
22 Sep 2015
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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 |
United Kingdom: 213
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Worldwide total number of subjects |
213
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EEA total number of subjects |
0
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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) |
213
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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) |
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 |
Healthy infants aged up to 13 weeks, due to receive their primary vaccinations as per the UK immunisation schedule with the exception of PCV13, were recruited via child health database mailouts in Oxfordshire and via GP surgeries in Gloucestershire and Hertfordshire, and were assesses for eligibility between 22/09/2015 and 1/11/2017. | |||||||||||||||
Pre-assignment
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Screening details |
376 infants were assessed for eligibility and 163 infants were excluded before randomisation. Infants with bleeding disorders, at risk of invasive pneumococcal disease, or with a history of allergic reactions to any of the vaccine components were excluded. 213 eligible infants were enrolled. | |||||||||||||||
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 |
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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Group 1 (2+1 PCV13) | |||||||||||||||
Arm description |
PCV13 schedule 2+1; both arms receive Bexsero 2+1 and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
PCV13
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Investigational medicinal product code |
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Other name |
Prevenar13
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
13 valent pneumococcal conjugate vaccine (PCV13) IM 0.5ml at 2, 4 and 12 months
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Investigational medicinal product name |
DTaP/IPV/Hib
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Investigational medicinal product code |
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Other name |
Infanrix-IPV-Hib
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
DTaP/IPV/Hib vaccine IM 0.5ml at 2, 3 and 4 months
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Investigational medicinal product name |
Rotavirus vaccine
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Investigational medicinal product code |
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Other name |
Rotarix
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Pharmaceutical forms |
Oral suspension in pre-filled oral applicator
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Routes of administration |
Oral use
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Dosage and administration details |
Rotavirus vaccine oral 1.5ml at 2 and 3 months
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Investigational medicinal product name |
4CMenB
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Investigational medicinal product code |
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Other name |
Bexsero
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
4-component Meningococcal B (4CMenB) vaccine IM 0.5ml given at 2, 4 and 12 months
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Investigational medicinal product name |
Meningococcal C/Hib vaccine
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Investigational medicinal product code |
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Other name |
Menitorix
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Pharmaceutical forms |
Powder and solvent for solution for injection in cartridge
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
Meningococcal C/Hib vaccine IM 0.5ml at 12 months
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Investigational medicinal product name |
Measles/Mumps/Rubella (MMR) vaccine
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Investigational medicinal product code |
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Other name |
Priorix or MMR II
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Pharmaceutical forms |
Powder and solvent for solution for injection in pre-filled syringe
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
Measles/Mumps/Rubella (MMR) vaccine IM 0.5ml at 13 months - Priorix or MMR II vaccine - depending on local availability and parental consent.
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Arm title
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Group 2 (1+1 PCV13) | |||||||||||||||
Arm description |
PCV13 schedule 1+1; both arms receive Bexsero and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
PCV13
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Investigational medicinal product code |
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Other name |
Prevenar13
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
13 valent pneumococcal conjugate vaccine (PCV13) IM 0.5ml at 3 and 12 months (instead of current routine schedule of 2,4 and 12 months)
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Investigational medicinal product name |
DTaP/IPV/Hib
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Investigational medicinal product code |
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Other name |
Infanrix-IPV-Hib
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
DTaP/IPV/Hib vaccine IM 0.5ml at 2, 3 and 4 months
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Investigational medicinal product name |
Rotavirus vaccine
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Investigational medicinal product code |
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Other name |
Rotarix
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Pharmaceutical forms |
Oral suspension in pre-filled oral applicator
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Routes of administration |
Oral use
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Dosage and administration details |
Rotavirus vaccine oral 1.5ml at 2 and 3 months
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Investigational medicinal product name |
4CMenB
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Investigational medicinal product code |
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Other name |
Bexsero
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
4-component Meningococcal B (4CMenB) vaccine IM 0.5ml given at 2, 4 and 12 months
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Investigational medicinal product name |
Meningococcal C/Hib vaccine
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Investigational medicinal product code |
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Other name |
Menitorix
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Pharmaceutical forms |
Powder and solvent for solution for injection in cartridge
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
Meningococcal C/Hib vaccine IM 0.5ml at 12 months
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Investigational medicinal product name |
Measles/Mumps/Rubella (MMR) vaccine
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Investigational medicinal product code |
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Other name |
Priorix or MMR II
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Pharmaceutical forms |
Powder and solvent for solution for injection in pre-filled syringe
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
Measles/Mumps/Rubella (MMR) vaccine IM 0.5ml at 13 months - Priorix or MMR II vaccine - depending on local availability and parental consent.
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Baseline characteristics reporting groups
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Reporting group title |
Group 1 (2+1 PCV13)
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Reporting group description |
PCV13 schedule 2+1; both arms receive Bexsero 2+1 and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2 (1+1 PCV13)
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Reporting group description |
PCV13 schedule 1+1; both arms receive Bexsero and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Group 1 (2+1 PCV13)
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Reporting group description |
PCV13 schedule 2+1; both arms receive Bexsero 2+1 and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix | ||
Reporting group title |
Group 2 (1+1 PCV13)
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Reporting group description |
PCV13 schedule 1+1; both arms receive Bexsero and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix |
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End point title |
Pneumococcal serotype specific GMCs - post booster | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Pneumococcal serotype specific geometric mean concentrations (GMCs) in blood samples following the completion of either a 2, 4 and 12 month schedule of PCV13 vaccination, or only 3 and 12 month PCV13 vaccination
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End point type |
Primary
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End point timeframe |
13 months of age
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Statistical analysis title |
Adjusted p-value | |||||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted in regression for sex and interval to blood
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Comparison groups |
Group 1 (2+1 PCV13) v Group 2 (1+1 PCV13)
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Number of subjects included in analysis |
177
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.0001 [1] | |||||||||||||||||||||||||||||||||||||||||||||||||||
Method |
Regression, Logistic | |||||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
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Notes [1] - Serotype (S) 1: <0.0001; S3: 0.57; S4: 0.047; S5: 0.20; S6A: 0.002; S6B: <0.0001; S7F: 0.059; S9V: 0.85; S14: 0.002; S18C: 0.017; S19A: 0.98; S19F: 0.035; S23F: <0.0001. |
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End point title |
GMC of serotype specific pneumococcal antibody responses and proportions ≥ 0.35 µg/mL - post primary vaccination | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
assess GMC of serotype specific pneumococcal antibody responses and proportions ≥ 0.35 µg/mL measured in the blood samples taken at 5 months of age, following one or two doses of 13 valent pneumococcal conjugate vaccine (PCV13) at 3 months or at 2 and 4 months of age
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End point type |
Secondary
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End point timeframe |
5 months of age
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No statistical analyses for this end point |
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End point title |
GMC of serotype specific pneumococcal antibody responses and proportions ≥ 0.35 µg/mL - post booster | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
assess GMC of serotype specific pneumococcal antibody responses and proportions ≥ 0.35 µg/mL measured in the blood samples taken at 13 months of age, following one or two doses of 13 valent pneumococcal conjugate vaccine (PCV13) at 3 months or at 2 and 4 months of age and a booster at 12 months of age
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End point type |
Secondary
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End point timeframe |
13 months of age
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No statistical analyses for this end point |
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End point title |
antibody responses to MenB vaccination: % hSBA titres ≥4 - post primary vaccination | |||||||||||||||||||||
End point description |
antibody responses to MenB vaccination using proportions achieving hSBA titres ≥4 for the three main MenB vaccine antigen target strains, 5/99 (NadA), NZ98/254 (PorA) and 44/76-SL (fHbp) in the blood samples taken at 5 months of age
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End point type |
Secondary
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End point timeframe |
5 months
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No statistical analyses for this end point |
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End point title |
antibody responses to MenB vaccination: % hSBA titres ≥4 - post booster | |||||||||||||||||||||
End point description |
antibody responses to MenB vaccination using proportions achieving hSBA titres ≥4 for the three main MenB vaccine antigen target strains, 5/99 (NadA), NZ98/254 (PorA) and 44/76-SL (fHbp) in the blood samples taken at 13 months of age
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End point type |
Secondary
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End point timeframe |
13 months of age
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No statistical analyses for this end point |
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End point title |
antibody responses to MenB vaccination: GMT - post primary vaccination | |||||||||||||||||||||
End point description |
antibody responses to MenB vaccination using GMTs for the three main MenB vaccine antigen target strains, 5/99 (NadA), NZ98/254 (PorA) and 44/76-SL (fHbp) in the blood samples taken at 5 months of age
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End point type |
Secondary
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End point timeframe |
5 months of age
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No statistical analyses for this end point |
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End point title |
antibody responses to MenB vaccination: GMT - post booster | |||||||||||||||||||||
End point description |
antibody responses to MenB vaccination using GMTs for the three main MenB vaccine antigen target strains, 5/99 (NadA), NZ98/254 (PorA) and 44/76-SL (fHbp) in the blood samples taken at 13 months of age
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End point type |
Secondary
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End point timeframe |
13 months of age
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No statistical analyses for this end point |
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End point title |
meningococcal serogroup C rSBA proportion titres ≥8 - post primary vaccination | ||||||||||||
End point description |
assess meningococcal serogroup C rSBA: proportion of infants with titres ≥8 from blood samples taken at 5 months of age
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End point type |
Secondary
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End point timeframe |
5 months of age
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No statistical analyses for this end point |
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End point title |
meningococcal serogroup C rSBA proportion titres ≥8 - post booster | |||||||||||||||
End point description |
assess meningococcal serogroup C rSBA: proportion of infants with titres ≥8 from blood samples taken at 13 months of age
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End point type |
Secondary
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End point timeframe |
13 months of age
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No statistical analyses for this end point |
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End point title |
meningococcal serogroup C rSBA GMT - post primary vaccination | |||||||||||||||
End point description |
assess meningococcal serogroup C rSBA GMTs from blood samples taken at 5 months of age
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End point type |
Secondary
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End point timeframe |
5 months of age
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No statistical analyses for this end point |
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End point title |
meningococcal serogroup C rSBA GMT - post booster | |||||||||||||||
End point description |
assess meningococcal serogroup C rSBA GMTs from blood samples taken at 13 months of age
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End point type |
Secondary
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End point timeframe |
13 months of age
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No statistical analyses for this end point |
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End point title |
antibody responses IgG GMC to Infanrix-IPV-Hib vaccine - post primary vaccination | |||||||||||||||||||||||||||||||||
End point description |
assess antibody responses, by IgG GMC to the tetanus and diphtheria components, as well as IgG GMCs against pertussis components (pertussis toxin (PT), pertactin (PRN), filamentous haemagglutinin (FHA) and fimbrial antigens (fims) 2 and 3), polyribosyl ribitol phosphate-Haemophilus influenzae type b (PRP-Hib) of Infanrix-IPV-Hib vaccine after three doses at 2, 3 and 4 months of age, from the blood sample taken at 5 months of age
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End point type |
Secondary
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End point timeframe |
5 months of age
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No statistical analyses for this end point |
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End point title |
antibody responses IgG GMC to Infanrix-IPV-Hib vaccine - post booster | |||||||||||||||||||||||||||||||||
End point description |
assess antibody responses by IgG GMC to the tetanus and diphtheria components, as well as IgG GMCs against pertussis components (pertussis toxin (PT), pertactin (PRN), filamentous haemagglutinin (FHA) and fimbrial antigens (fims) 2 and 3), polyribosyl ribitol phosphate-Haemophilus influenzae type b (PRP-Hib) of Infanrix-IPV-Hib vaccine after three doses at 2, 3 and 4 months of age, from the blood sample taken at 13 months of age
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End point type |
Secondary
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End point timeframe |
13 months of age
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No statistical analyses for this end point |
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End point title |
antibody responses proportions above correlates of protection to Infanrix-IPV-Hib vaccine - post primary vaccination | ||||||||||||||||||||||||||||||
End point description |
assess antibody responses, presented as percentage of participants with IgG to Diphtheria-toxoid, Tetanus-toxoid and polyribosyl ribitol phosphate (PRP - Hib) above correlates of protection, of Infanrix-IPV-Hib vaccine after three doses at 2, 3 and 4 months of age, from the blood sample taken at 5 months of age
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End point type |
Secondary
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End point timeframe |
5 month of age
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No statistical analyses for this end point |
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End point title |
antibody responses proportions above correlates of protection to Infanrix-IPV-Hib vaccine - post booster | ||||||||||||||||||||||||||||||
End point description |
assess antibody responses, presented as percentage of participants with IgG to Diphtheria-toxoid, Tetanus-toxoid and polyribosyl ribitol phosphate (PRP - Hib) above correlates of protection, of Infanrix-IPV-Hib vaccine after three doses at 2, 3 and 4 months of age, from the blood sample taken at 13 months of age
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End point type |
Secondary
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End point timeframe |
13 months of age
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No statistical analyses for this end point |
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End point title |
reactogenicity using a daily health diary for a week following vaccination | |||||||||
End point description |
assess reactogenicity using a daily health diary for a week following vaccination at 2, 3, 4 and 12 months of age to record local reactions and systemic symptoms, particularly with reference to the use of paracetamol as indicated when the MenB vaccine, Bexsero, is administered. Temperature will also be recorded and analysed from the iButton system
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End point type |
Secondary
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End point timeframe |
for a week following vaccination at 2, 3, 4 and 12 months of age
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Attachments |
Local and systemic reactions |
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No statistical analyses for this end point |
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End point title |
Pneumococcal serotype specific GMCs - post primary vaccination | |||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Pneumococcal serotype specific geometric mean concentrations (GMC) in blood samples at 5 months of age (1 month post the primary series of PCV13 vaccination for group 1 and 2 months post the single priming dose for group 2)
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End point type |
Secondary
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End point timeframe |
5 months of age
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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 |
for a week following each vaccination appointment at 2, 3, 4 and 12 months of age
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Adverse event reporting additional description |
Safety data in terms of SAEs, is collected at each visit for the preceding period, with details verified from GP notes. Parents are asked to complete a health diary for the week following each vaccination appointment to document local reactions (redness/swelling/ pain at the injection site) as well as any systemic symptoms and use of paracetamol.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
v6.0
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Reporting groups
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Reporting group title |
Group 1 (2+1 PCV13)
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Reporting group description |
PCV13 schedule 2+1 and all participants in both arms receiving Bexsero 2+1 and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Group 2 (1+1 PCV13)
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Reporting group description |
PCV13 schedule 1+1 and all participants at both arms receiving Bexsero and Infanrix/IPV/Hib with one MenC conjugate vaccination at 12 months given as the combined Hib/MenC conjugate vaccine, Menitorix | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Notes [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: The number of subjects does not match due to combination of withdrawal and missing diary card data. |
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
21 Oct 2015 |
.The principal investigators have been updated on page 1
.The type of laboratory assays performed for meningococcal serogroup C and W at 5 months of age (secondary objectives and endpoints) have been revised on pages 9,11,18 and 38
.Clarification of the timings to assess antibody responses to Men B, tetanus, diphtheria and pertussis on pages 9,11,18 and 38
.The titre thresholds for different type of assays have been clarified on pages 9, 11, 18 and 38 .Clarification that reactogenicity data will only be collected following immunizations at 2, 3, 4 and 12 months of age on pages 10, 12, 18, 28 and 38
.Clarification of the references used to define the protective levels of antibodies to Men B vaccine and PCV13 on page 28
.Clarification of the laboratory responsible for processing NP swabs on pages 31 and 32
.Removal of functional pertussis antibody studies on page 31
.Clarification of the name of the sample storage facility at PHE on page 32
.Clarification of the data analysis, including an interim analysis on page 40
.Clarification of the location of the Clinical Trial Data Manager on page 41
.The guidelines followed by the study laboratories have been updated on page 43
.Update of references on page45.
.Clarification of PHE recruitment methods on page 23. |
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12 Jan 2018 |
.The study has been extended. The final visit (visit 8) will now be when participants are 21-33months of age (instead of 18 months of age). The extension involves an additional visit and a blood test. This will allow an extended description of antibody responses to the vaccines given in this trial, which has been listed as an additional secondary endpoint.
.Participants will be recruited from all study areas (Thames Valley, Gloucestershire and Hertfordshire).
.The PI for the PHE sites in Gloucestershire and Hertfordshire has also changed. |
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12 Feb 2018 |
.Increase maximal blood volume taken at visit 8 from 5mL to 8mL.
.Remove increased body temperature from the temporary exclusion criteria for visit 8.
.Change laboratory processes for visit 8, now all samples will be shipped to OVG, spun, frozen and then either stored or sent to other sites for analysis. |
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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. | |||
Follow up results are confidential and not reported. Paper is in draft, will be published soon and distributed to participants. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/29174323 http://www.ncbi.nlm.nih.gov/pubmed/33428870 |