Baby Vaccine Study (Sched3)

September 17, 2021 updated by: University of Oxford

Assessment of Post Booster Antibody Responses in UK Infants Given a Reduced Priming Schedule of Meningococcal Serogroup B and 13 Valent Pneumococcal Conjugate Vaccines

This multicentre, parallel group, block randomised clinical trial aims to investigate the post booster antibody response in UK infants given a reduced priming schedule of meningococcal serogroup B vaccine and 13 valent pneumococcal conjugate vaccine. It will provide information about how best to include the meningococcal B vaccine (likely to be introduced late 2015) into the routine immunisation schedule.

The UK Department of Health provides a routine vaccination schedule for children in the UK and are advised by the Joint Committee on Vaccination and Immunisation (JCVI). The Department of Health have announced that the meningococcal B vaccine (Bexsero) be introduced to the routine schedule as a 2+1 schedule. Cost effectiveness could also be improved by removing the current MenC conjugate vaccine dose given at 3 months of age. There is no published immunogenicity data for Bexsero when given at 2, 4 and 12 months of age (2+1 schedule) and with concomitant Infanrix/IPV/Hib which has now replaced Pediacel in the infant programme.

This change to the schedule would result in three injections at 2, 4 and 12 months, and given previous reluctance among parents for three injections at one visit, an option to reduce PCV13 to a 1+1 schedule (priming dose at 3 months and booster at 12 months) will be assessed in this study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study's primary objective is to assess antibody response to the pneumococcal vaccine after the final infant vaccinations at approximately 13 months of age, and secondary objectives include antibody response following meningococcal B and C vaccines, tetanus, diphtheria and pertussis vaccines. In addition, the effect of maternal pertussis vaccination in pregnancy on infant immune response to vaccines, the prevalence of carriage of pneumococcal serotypes at 12 and 18 months of age and reactogenecity following each vaccine will be assessed.

200 healthy children who have not yet received their routine infant immunisations will be enrolled between 8 and 12 weeks old. Participants will be randomised into one of two groups with differing vaccine schedules. Children in both groups will receive their routine immunisations with the following changes: the addition of 3 doses of a meningococcal B vaccine at 2, 4 and 12 months and a meningococcal C vaccine at 12 months only (instead of a dose at 3 and 12 months). The 2 groups will differ by the number of doses of the 13-valent pneumococcal vaccine (PCV13); to be given either at 2, 4, and 12 months of age (as currently given in the routine schedule) or at 3 and 12 months of age.

Each participant will have 2 blood tests: at 5 and 13 months of age, and 2 nose swabs: at 12 and 18 months of age to address the objectives of the study. Parents will be asked to complete a health diary to record any adverse events in the 7 days following vaccinations and a continuous thermometer (ibutton) will be used to record the temperature for 24 hours after each vaccination.

If the blood samples at 13 months reveal antibody titres that are below the level indicative of protection, a recommendation will be made for booster vaccinations.

Study Type

Interventional

Enrollment (Actual)

189

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 7LE
        • Centre for Clinical Vaccinology and Tropical Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 2 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Infants due to receive their primary immunisations , aged up to 13 weeks on first vaccinations.
  • Written informed consent given by mother who is aged >= 16 years [NB mother is preferable as consent also allows permission to record the date of pertussis immunisation in pregnancy, which may need to be verified in her medical record. Where mother is not available, consent may be taken from father or legal guardian and maternal pertussis status noted as not known]

Exclusion Criteria:

  • Bleeding disorder
  • Fulfil any of the contraindications to vaccination as specified in The Green Book [https://www.gov.uk/government/organisations/public-health-england/series/immunisation-against-infectious-disease-the-green-book]:
  • At risk of invasive pneumococcal disease (IPD) as defined in the Green Book pneumococcal chapter and those born prior to 37 weeks gestation
  • Confirmed anaphylactic reaction to a previous dose of the vaccine, or
  • Confirmed anaphylactic reaction to any constituent or excipient of the vaccine(s).
  • A confirmed anaphylactic reaction to neomycin, streptomycin or polymyxin B (which may be present in trace amounts in the tetanus vaccine) and/or kanamycin, histidine, sodium chloride or sucrose (which may be present in trace amounts in the MenB vaccine).
  • Latex hypersensitivity (the syringe cap of Bexsero may contain natural rubber latex)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Group 1

Group 1 will receive the following interventions:

  • DTaP/IPV/Hib vaccine IM 0.5ml at 2, 3 and 4 months
  • 13 valent pneumococcal conjugate vaccine (PCV13) IM 0.5ml at 2, 4 and 12 months
  • Rotavirus vaccine oral 1.5ml at 2 and 3 months
  • 4-component Meningococcal B (4CMenB) vaccine IM 0.5ml given at 2, 4 and 12 months
  • Meningococcal C/Hib vaccine IM 0.5ml at 12 months
  • Measles/Mumps/Rubella (MMR) vaccine IM 0.5ml at 13 months
Biological: DTaP/IPV/Hib vaccine
Given at 2, 3 and 4 months to Group 1 and 2
Other Names:
  • Infanrix-IPV-Hib
Biological: 13 valent Pneumococcal Conjugate Vaccine
Given at 2,4 and 12 months in group 1, given at 3 and 12 months in group 2
Other Names:
  • Prevenar
  • PCV 13
Biological: Rotavirus vaccine
Given at 2 and 3 months to Group 1 and 2
Other Names:
  • Rotarix
Biological: 4-component Meningococcal B vaccine
Given at 2, 4 and 12 months to Group 1 and 2
Other Names:
  • Bexsero
Biological: Meningococcal C/Hib vaccine (MenC/Hib vaccine)
Given at 12 months to Group1 and 2
Other Names:
  • Menitorix
Biological: Measles/Mumps/Rubella Vaccine (MMR vaccine)
Given at 13 months to Groups 1 and 2
Other Names:
  • Priorix
  • MMR II
Other: Group 2

Group 2 will receive the following interventions:

  • DTaP/IPV/Hib vaccine IM 0.5ml at 2, 3 and 4 months
  • 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)
  • Rotavirus vaccine oral 1.5ml at 2 and 3 months
  • 4-component Meningococcal B (4CMenB) vaccine IM 0.5ml given at 2, 4 and 12 months
  • Meningococcal C/Hib vaccine IM 0.5ml at 12 months
  • Measles/Mumps/Rubella (MMR) vaccine IM 0.5ml at 13 months
Biological: DTaP/IPV/Hib vaccine
Given at 2, 3 and 4 months to Group 1 and 2
Other Names:
  • Infanrix-IPV-Hib
Biological: 13 valent Pneumococcal Conjugate Vaccine
Given at 2,4 and 12 months in group 1, given at 3 and 12 months in group 2
Other Names:
  • Prevenar
  • PCV 13
Biological: Rotavirus vaccine
Given at 2 and 3 months to Group 1 and 2
Other Names:
  • Rotarix
Biological: 4-component Meningococcal B vaccine
Given at 2, 4 and 12 months to Group 1 and 2
Other Names:
  • Bexsero
Biological: Meningococcal C/Hib vaccine (MenC/Hib vaccine)
Given at 12 months to Group1 and 2
Other Names:
  • Menitorix
Biological: Measles/Mumps/Rubella Vaccine (MMR vaccine)
Given at 13 months to Groups 1 and 2
Other Names:
  • Priorix
  • MMR II

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: Blood samples collected at 13 months of age
pneumococcal IgG concentration for the 13 serotypes contained in the vaccine
Blood samples collected at 13 months of age

Secondary Outcome Measures

Outcome Measure
Time Frame
13 serotype-specific pneumococcal IgG GMCs and functional pneumococcal antibodies and proportions greater than or equal to ≥0.35µg/mL for each serotype in blood samples taken at 5 and 13 months
Time Frame: blood samples taken at 5 and 13 months
blood samples taken at 5 and 13 months
Titres and proportions of participants achieving antibody responses to MenB vaccination human Serum Bactericidal Antibody (SBA) titres ≥4 for the three main vaccine antigen target MenB strains, 5/99 (NadA), NZ98/254 (PorA) and 44/76-SL (fHbp)
Time Frame: Blood samples taken at 5 months
Blood samples taken at 5 months
Meningococcal serogroup C human SBA geometric mean titres (GMTs) and proportion of infants ≥4 (5 month blood only); rabbit SBA titres (GMT) and proportion of infants with titres 8 and 128 (13 month blood only)
Time Frame: blood samples taken at 5 months and 13 months
blood samples taken at 5 months and 13 months
Meningococcal serogroup W hSBA GMTs and proportion of infants with titre ≥4 at 5 and 13 months of age
Time Frame: blood samples taken at 5 and 13 months
blood samples taken at 5 and 13 months
GMC of anti-PRP IgG [Hib antigen] and proportion of infants with concentrations of > 0.15µg/mL and 1.0µg/mL in the blood samples taken at 5 and 13 months of age
Time Frame: Blood samples taken at 5 and 13 months of age
Blood samples taken at 5 and 13 months of age
GMC of IgG to pertussis antigens (PT, PRN, FHA and FIM 2 and 3) in the blood samples taken at 5 months of age
Time Frame: Blood samples taken at 5 months of age
Blood samples taken at 5 months of age
GMC of anti-tetanus toxoid IgG and proportions ≥0.1 IU/mL and ≥1.0 IU/mL in the blood samples taken at 5 months of age
Time Frame: Blood samples taken at 5 months of age
Blood samples taken at 5 months of age
GMC of anti-diphtheria toxoid IgG and proportions ≥0.1IU/mL and ≥1.0 IU/mL in the blood samples taken at 5 months of age
Time Frame: blood samples taken at 5 months of age
blood samples taken at 5 months of age
Frequency of carriage of identified pneumococcal serotypes from the nasal swab collected prior to the booster vaccinations at 12 months of age and six months later
Time Frame: Nasal swab taken at 12 months and 18 months
Nasal swab taken at 12 months and 18 months
Number of participants with local adverse events at injection site and temperature as recorded in the daily health diary for the week following vaccination and any systemic symptoms. Temperature also recorded and analysed from the iButton system
Time Frame: Measurements following vaccinations at 2, 3, 4, 12 and 13 months of age
Measurements following vaccinations at 2, 3, 4, 12 and 13 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Collaborators

University College, London
Public Health England

Investigators

  • Principal Investigator: Matthew D Snape, Oxford Vaccine Group, Chief Investigator

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Actual)

November 1, 2017

Study Completion (Actual)

June 1, 2021

Study Registration Dates

First Submitted

June 16, 2015

First Submitted That Met QC Criteria

June 23, 2015

First Posted (Estimate)

June 26, 2015

Study Record Updates

Last Update Posted (Actual)

September 20, 2021

Last Update Submitted That Met QC Criteria

September 17, 2021

Last Verified

September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OVG2015/03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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