Baby Vaccine Study (Sched3)

NCT02482636 | Completed Phase 2

• 1 other identifier: OVG2015/03
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infectious Diseases

Keywords

infant immunisations; vaccines; paediatric; pneumococcal; meningococcal

Outcome Measures

Primary Outcomes (1)

• 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

  pneumococcal IgG concentration for the 13 serotypes contained in the vaccine

  Blood samples collected at 13 months of age

Secondary Outcomes (10)

• 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

  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)

  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)

  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

  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

  Blood samples taken at 5 and 13 months of age

Study Arms (2)

Group 1

OTHER

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; Biological: 13 valent Pneumococcal Conjugate Vaccine; Biological: Rotavirus vaccine; Biological: 4-component Meningococcal B vaccine; Biological: Meningococcal C/Hib vaccine (MenC/Hib vaccine); Biological: Measles/Mumps/Rubella Vaccine (MMR vaccine)

Group 2

OTHER

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; Biological: 13 valent Pneumococcal Conjugate Vaccine; Biological: Rotavirus vaccine; Biological: 4-component Meningococcal B vaccine; Biological: Meningococcal C/Hib vaccine (MenC/Hib vaccine); Biological: Measles/Mumps/Rubella Vaccine (MMR vaccine)

Interventions

DTaP/IPV/Hib vaccine BIOLOGICAL

Given at 2, 3 and 4 months to Group 1 and 2

Also known as: Infanrix-IPV-Hib

Group 1; Group 2

13 valent Pneumococcal Conjugate Vaccine BIOLOGICAL

Given at 2,4 and 12 months in group 1, given at 3 and 12 months in group 2

Also known as: PCV 13, Prevenar

Group 1; Group 2

Rotavirus vaccine BIOLOGICAL

Given at 2 and 3 months to Group 1 and 2

Also known as: Rotarix

Group 1; Group 2

4-component Meningococcal B vaccine BIOLOGICAL

Given at 2, 4 and 12 months to Group 1 and 2

Also known as: Bexsero

Group 1; Group 2

Meningococcal C/Hib vaccine (MenC/Hib vaccine) BIOLOGICAL

Given at 12 months to Group1 and 2

Also known as: Menitorix

Group 1; Group 2

Measles/Mumps/Rubella Vaccine (MMR vaccine) BIOLOGICAL

Given at 13 months to Groups 1 and 2

Also known as: Priorix, MMR II

Group 1; Group 2

Eligibility Criteria

• Age: 8 Weeks - 12 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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 \[NB mother is preferable as consent also allows permission to record the date of pertussis immunisation in pregnancy, which may need to be verified in her medical record. Where mother is not available, consent may be taken from father or legal guardian and maternal pertussis status noted as not known\]

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Oxford: lead
• University College, London: collaborator
• Public Health England: collaborator

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

Related Publications (3)

• Goldblatt D, Southern J, Andrews NJ, Burbidge P, Partington J, Roalfe L, Valente Pinto M, Thalasselis V, Plested E, Richardson H, Snape MD, Miller E. Pneumococcal conjugate vaccine 13 delivered as one primary and one booster dose (1 + 1) compared with two primary doses and a booster (2 + 1) in UK infants: a multicentre, parallel group randomised controlled trial. Lancet Infect Dis. 2018 Feb;18(2):171-179. doi: 10.1016/S1473-3099(17)30654-0. Epub 2017 Nov 22.

  PMID: 29174323 BACKGROUND

• Davis K, Valente Pinto M, Andrews NJ, Goldblatt D, Borrow R, Findlow H, Southern J, Partington J, Plested E, Patel S, Holland A, Matheson M, England A, Hallis B, Miller E, Snape MD. Immunogenicity of the UK group B meningococcal vaccine (4CMenB) schedule against groups B and C meningococcal strains (Sched3): outcomes of a multicentre, open-label, randomised controlled trial. Lancet Infect Dis. 2021 May;21(5):688-696. doi: 10.1016/S1473-3099(20)30600-9. Epub 2021 Jan 8.

  PMID: 33428870 DERIVED

• Valente Pinto M, Davis K, Andrews N, Goldblatt D, Borrow R, Southern J, Nordgren IK, Vipond C, Plested E, Miller E, Snape MD. Understanding the reactogenicity of 4CMenB vaccine: Comparison of a novel and conventional method of assessing post-immunisation fever and correlation with pre-release in vitro pyrogen testing. Vaccine. 2020 Nov 17;38(49):7834-7841. doi: 10.1016/j.vaccine.2020.10.023. Epub 2020 Oct 24.

  PMID: 33109390 DERIVED

MeSH Terms

Conditions

Communicable Diseases

Interventions

diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine; 13-valent pneumococcal vaccine; Heptavalent Pneumococcal Conjugate Vaccine; Rotavirus Vaccines; RIX4414 vaccine; 4CMenB vaccine; Measles-Mumps-Rubella Vaccine

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pneumococcal Vaccines; Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Vaccines, Combined; Viral Vaccines; Measles Vaccine; Mumps Vaccine; Rubella Vaccine

Study Officials

• Matthew D Snape

  Oxford Vaccine Group, Chief Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2015
• First Posted: June 26, 2015
• Study Start: August 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: June 1, 2021
• Last Updated: September 20, 2021

Record last verified: 2021-09

Locations

GB (1)