13 Valent Pneumococcal Conjugate Vaccine - Follow-on Study

A follow-on, Multi-centre, Open-label, Clinical, Phase 4 Trial to Investigate the Persistence of Serotype-specific Antibodies at 40 Months of Age in Children Who Have Received Either the 7-valent or the 13-valent Pneumococcal Conjugate Vaccine at 2, 4 and 12 Months of Age and Assessing the Immunogenicity of a 13-valent Pneumococcal Conjugate Vaccine Booster Dose Given at 40 Months of Age

This is a follow-on, multi-centre, open-label, clinical trial. The purpose of this trial is to investigate the concentrations of serotype-specific antibodies to IgG included in PCV13 in children who have received either the PCV7 or PCV13 primary immunisation at 2, 4 and 12 months of age. We intend to recruit all interested participants who completed the Wyeth-sponsored PCV13 infant trial study (6096A1-007) at selected study sites (i.e. those that recruited the majority of the children in the original study). The study will start in March 2010, at which time the eldest participants in the 6096A1-007 study will be approximately 42 months of age. There will be two visits per participant, 1 month apart from each other. At visit one, all participants will have a blood test and receive a dose of PCV13. At visit 2, all participants will have a blood test and will be offered the remaining pre-school booster vaccinations unless they have already received them.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Disease
• Intervention / Treatment: Biological: PCV13

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom
    • Bristol Children's Vaccine Centre, University of Bristol
  • London, United Kingdom
    • St George's Vaccine Institute, University of London
  • Oxford, United Kingdom, OX3 7LJ
    • Oxford Vaccine Group, Dept Paediatrics, University of Oxford
  • Southampton, United Kingdom
    • Wellcome Trust Clinical Research Facility, University of Southampton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant completed the Wyeth-sponsored PCV13 infant trial study (6096A1-007) at one of the study sites participating in this follow-on study.
2. Aged 39-46 months (inclusive) at time of enrolment.
3. Available for entire study period and whose parent/legal guardian can be reached by telephone.
4. Healthy children as determined by medical history, physical examination, done by a study nurse (and/or study doctor if required, depending on the medical history of the participant and physical assessment), and judgment of the investigator.
5. Parent/legal guardian must be able to complete all relevant study procedures during study participation.

Exclusion Criteria:

1. Has received further doses of pneumococcal vaccination with licensed or investigational pneumococcal vaccine other than those given as part of the Wyeth-sponsored PCV13 infant trial study (6096A1-007).
2. A previous anaphylactic reaction to any vaccine or vaccine-related component.
3. Contraindication to vaccination with pneumococcal conjugate vaccine.
4. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
5. Known or suspected immune deficiency or suppression.
6. History of culture-proven invasive disease caused by S pneumoniae.
7. Major known congenital malformation or serious chronic disorder.
8. Significant neurologic disorder or history of seizures including febrile seizure, or significant stable or evolving disorders such as cerebral palsy, encephalopathy, hydrocephalus, or other significant disorder.
9. Receipt of blood products or gamma-globulin (including hepatitis B immunoglobulin and monoclonal antibodies; eg, synagisB).
10. Participation in another investigational study other than the Wyeth-sponsored PCV13 infant trial study (6096A1-007). Participation in purely observational studies is acceptable.
11. Child who is a direct descendant (child, grandchild) of the study site personnel.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCV13; Initial vaccination with PCV13	Biological: PCV13; Immunisation with the 13-valent pneumococcal conjugate vaccine (PCV13) at approximately 40 months of age.; Other Names: 13-valent pneumococcal conjugate vaccine
Experimental: PCV7; Initial intervention with PCV7	Biological: PCV13; Immunisation with the 13-valent pneumococcal conjugate vaccine (PCV13) at approximately 40 months of age.; Other Names: 13-valent pneumococcal conjugate vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the effectiveness of PCV13 booster vaccinations	To assess the proportion of participants, immunised with the 13-valent pneumococcal conjugate vaccine (PCV13) at 2, 4 and 12 months of age, who have IgG concentrations ≥ 0.35mcg/ml for PCV13 serotypes at the time when preschool booster vaccinations are due (at 40 months of age).	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess IgG concentrations for PCV13 serotypes in children immunised with PCV7 and PCV13	To assess the proportion of participants, immunised with the 7-valent pneumococcal conjugate vaccine (PCV7) at 2, 4 and 12 months of age, who have IgG concentrations ≥ 0.35mcg/ml for PCV13 serotypes at the time when preschool booster vaccinations are due (at 40 months of age) and comparing these to the proportion of participants achieving this threshold after infant immunisation with PCV 13.	1 month
Compare PCV13 serotype-specific IgG geometric mean concentrations, opsonophagocytic activity geometric mean titres & the proportion of participants with PCV13 serotype-specific OPA titres ≥ 1:8 (at 40 months) when immunised in infancy with PCV7 or PCV13.		1 month
Compare PCV serotype-specific IgG GMCs, OPA GMTs & proportion of participants with IgG concs ≥ 0.35mcg/ml & OPA titres ≥ 1:8 one month after booster dose of PCV13 at 40 months in children previously immunised with PCV7 & PCV13 at 2,4 & 12 months.		1 month
To determine reactogenicity of the pre-school PCV13 booster in terms of rates of local and systemic reactions following vaccination.		1 month
Investigate influence of genetic polymorphisms on the above immunological markers following infant immunisation with PCV7/PCV13 & following booster dose of PCV13 at 40 months & on the nature of adverse reactions observed after booster.		1 month
Measure pneumococcal serotype-specific memory B cells frequencies before & 1 month after PCV13 dose (40 months) in subset previously immunised with PCV7/PCV13 at 2,4 & 12 months (serotype studies to include 4,14,23F (present in PCV7) & 1,3,19A).		1 month

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: University of Southampton; University of Bristol; University of London

Publications and helpful links

General Publications

• Truck J, Thompson A, Morales-Aza B, Clutterbuck EA, Voysey M, Clarke E, Snape MD, Kelly DF, Finn A, Pollard AJ. Memory B cell response to a PCV-13 booster in 3.5year old children primed with either PCV-7 or PCV-13. Vaccine. 2017 May 9;35(20):2701-2708. doi: 10.1016/j.vaccine.2017.03.079. Epub 2017 Apr 6.
• Truck J, Snape MD, Tatangeli F, Voysey M, Yu LM, Faust SN, Heath PT, Finn A, Pollard AJ. Pneumococcal serotype-specific antibodies persist through early childhood after infant immunization: follow-up from a randomized controlled trial. PLoS One. 2014 Mar 11;9(3):e91413. doi: 10.1371/journal.pone.0091413. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: March 26, 2010
• First Submitted That Met QC Criteria: March 29, 2010
• First Posted (Estimate): March 30, 2010

Study Record Updates

• Last Update Posted (Estimate): March 22, 2011
• Last Update Submitted That Met QC Criteria: March 21, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: 7 valent Pneumococcal conjugate vaccine; 13 valent Pneumococcal conjugate vaccine; PCV13; PCV7
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 2009/04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No