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The Effect of Fractional Doses of Pneumococcal Conjugate Vaccines on Immunogenicity and Carriage in Kenyan Infants (FPCV)

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ClinicalTrials.gov Identifier: NCT03489018
Recruitment Status : Not yet recruiting
First Posted : April 5, 2018
Last Update Posted : February 28, 2019
Sponsor:
Collaborators:
University College, London
KEMRI-Wellcome Trust Collaborative Research Program
Bill and Melinda Gates Foundation
National Institute of Health Research (NIHR) Mucosal Pathogens Research Unit (MPRU)
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Brief Summary:

Before the introduction of pneumonia vaccines in 2000, between 700,000 - 1 million children died each year as a result of infection with the bacteria Streptococcus pneumoniae and the resulting diseases, namely, meningitis, sepsis and pneumonia. Most of the deaths were in Africa and Asia. Where the vaccines have been introduced, they have been highly effective and have already reduced disease. However, at 10 USD per child, they are not affordable to most low-income countries without financial support from Gavi, the Vaccine Alliance.

This project aims to assess whether lower doses of the two commercially available pneumonia vaccines can protect Kenyan infants as well as the full dose. The results could be used to increase the affordability of the pneumonia vaccine, and enable delivery of the vaccine to continue in the absence of Gavi support.


Condition or disease Intervention/treatment Phase
Pneumococcal Infection Streptococcus Pneumoniae Infection Invasive Pneumococcal Disease, Protection Against Biological: PCV10 Biological: PCV13 Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Participants will be randomised to one of seven groups for the duration of the study:

A. Full dose PCV13 vaccination in a 2p+1 schedule; B. 40% fractional dose PCV13 vaccination in a 2p+1 schedule; C. 20% fractional dose PCV13 vaccination in a 2p+1 schedule; D. Full dose PCV10 vaccination in a 2p+1 schedule; E. 40% fractional dose PCV10 vaccination in a 2p+1 schedule; F. 20% fractional dose PCV10 vaccination in a 2p+1 schedule; G. Full dose PCV10 vaccination in a 3p+0 schedule.

Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Participants, parents of participants and all of the study team apart from the vaccinator will be masked with respect to the infant's allocation to a trial arm between A-F. If randomly allocated to trial arm G, parents and study personnel will be unmasked due to the necessity for trial arm G to receive a different vaccine schedule compared to trial arms A-F. It is thought that this unmasking will have minimal impact on retention, follow up and outcome assessment across the trial arms for primary and secondary outcomes.
Primary Purpose: Prevention
Official Title: The Effect of Fractional Doses of Pneumococcal Conjugate Vaccines (PCV10 and PCV13) on Immunogenicity and Vaccine-serotype Carriage in Kenyan Infants
Estimated Study Start Date : March 30, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : May 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Full dose PCV13 (2p+1 schedule)
Full dose PCV13 administration in 2p+1 schedule
Biological: PCV13
Experimental arms will receive a lower dose of the intervention than the marketed dose.
Other Names:
  • Prevnar 13 (Pfizer Inc.)
  • 13-valent pneumococcal conjugate vaccine
  • Prevnar13

Experimental: 40% dose PCV13 (2p+1 schedule)
Fractional (40%) dose PCV13 administration in 2p+1 schedule
Biological: PCV13
Experimental arms will receive a lower dose of the intervention than the marketed dose.
Other Names:
  • Prevnar 13 (Pfizer Inc.)
  • 13-valent pneumococcal conjugate vaccine
  • Prevnar13

Experimental: 20% dose PCV13 (2p+1 schedule)
Fractional (20%) dose PCV13 administration in 2p+1 schedule
Biological: PCV13
Experimental arms will receive a lower dose of the intervention than the marketed dose.
Other Names:
  • Prevnar 13 (Pfizer Inc.)
  • 13-valent pneumococcal conjugate vaccine
  • Prevnar13

Active Comparator: Full dose PCV10 (2p+1 schedule)
Full dose PCV10 administration in 2p+1 schedule
Biological: PCV10
Experimental arms will receive a lower dose of the intervention than the marketed dose.
Other Names:
  • Synflorix (GlaxoSmithKline plc.)
  • 10-valent pneumococcal conjugate vaccine

Experimental: 40% dose PCV10 (2p+1 schedule)
Fractional (40%) dose PCV10 administration in 2p+1 schedule
Biological: PCV10
Experimental arms will receive a lower dose of the intervention than the marketed dose.
Other Names:
  • Synflorix (GlaxoSmithKline plc.)
  • 10-valent pneumococcal conjugate vaccine

Experimental: 20% dose PCV10 (2p+1 schedule)
Fractional (20%) dose PCV10 administration in 2p+1 schedule
Biological: PCV10
Experimental arms will receive a lower dose of the intervention than the marketed dose.
Other Names:
  • Synflorix (GlaxoSmithKline plc.)
  • 10-valent pneumococcal conjugate vaccine

Active Comparator: Full dose PCV10 (3p+0 schedule)
The current vaccine (PCV10) and schedule (3p+0) in use in the Kenyan routine immunisation programme as an additional comparison arm.
Biological: PCV10
Experimental arms will receive a lower dose of the intervention than the marketed dose.
Other Names:
  • Synflorix (GlaxoSmithKline plc.)
  • 10-valent pneumococcal conjugate vaccine




Primary Outcome Measures :
  1. Immunogenicity: The ratio of IgG GMCs at 1-month post boost [ Time Frame: 4-weeks post-boost (approximately 10 months of age) ]
    The ratio of the geometric mean concentrations of IgG after vaccination with 3 full or fractional doses of PCV


Secondary Outcome Measures :
  1. Immunogenicity: the proportion of children who 'seroconvert' to vaccine-serotypes after vaccination [ Time Frame: 4-weeks post-primary series (approximately 18 weeks of age) ]
    The proportion of children with vaccine-serotype specific IgG antibody concentrations more than or equal to 0.35 mcg/ml after vaccination

  2. The proportion of children with evidence of vaccine-serotype carriage [ Time Frame: Approximately 18 months of age ]
    Vaccine-type carriage prevalence across arms

  3. The proportion of children with evidence of vaccine-serotype carriage [ Time Frame: Approximately 9 months of age ]
    Vaccine-type carriage prevalents across arms

  4. The direct vaccine effectiveness of full/fractional doses of PCV13 against carriage of serotypes 6A and 19A [ Time Frame: Approximately 18 months of age ]
    The direct effectiveness of full/fractional doses of PCV13 in preventing carriage of serotypes 6A and 19A compared to that of full dose PCV10

  5. Opsonophagocytic activity of vaccine-induced antibody to 4 serotypes [ Time Frame: Approximately 18 months of age ]
    Functionality of the antibody response


Other Outcome Measures:
  1. Immunogenicity: the geometric mean concentration (GMC) of serotype-specific IgG [ Time Frame: 4-weeks post-primary series (approximately 18 weeks of age) ]
    IgG GMCs elicited post-primary series

  2. Safety: the prevalence of adverse events following immunisation by arm [ Time Frame: Infants 6weeks-18 months of age ]
    The proportion fo children with adverse events following immunisation by arm

  3. Immunogenicity: The geometric mean concentration (GMC) of serotype-specific IgG after the primary series of the 2p+1 schedule, prior to boost (9 months of age) and at the end of study follow-up at 18 months of age. [ Time Frame: Approximately 9 and 18 months of age ]
    IgG GMCs at 9 and 18 months of age



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Weeks to 8 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy infants aged 6-8 weeks of age (HIV positive or negative but with no symptoms of current clinical immunosuppression i.e. HIV infection at WHO clinical stage 1);
  • Parents are willing to provide informed consent for their child to participate in the study
  • Parents and infant are likely to remain in the study area until the infant is 18 months of age and comply with study requirements including the requirement to return to the same health facility to obtain all other childhood vaccines.

Exclusion Criteria:

  • Infants >8 weeks of age at time of enrolment
  • Signs or symptoms of immunosuppression or HIV infection clinical stage 2 or above.
  • Acute illness (e.g. febrile disease) on the day of vaccination
  • Contraindications precluding vaccination (e.g. hypersensitivity to any component of the vaccine, including diphtheria toxoid)
  • Previous PCV vaccination
  • Family are planning to migrate out of the study areas before the end of the study follow-up
  • Family are planning to obtain the subsequent vaccine doses of the routine immunisation schedule elsewhere and therefore their child may receive a full dose under the routine vaccination programme.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03489018


Contacts
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Contact: Katherine E. Gallagher, PhD +254707867625 katherine.gallagher@lshtm.ac.uk
Contact: J. Anthony G. Scott, DTMH FMedSci +254709983677

Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
University College, London
KEMRI-Wellcome Trust Collaborative Research Program
Bill and Melinda Gates Foundation
National Institute of Health Research (NIHR) Mucosal Pathogens Research Unit (MPRU)
Investigators
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Principal Investigator: J. Anthony G Scott, DTMH FMedSci London School of Hygiene & Tropical Medicine, Keppel Street, London
  Study Documents (Full-Text)

Documents provided by London School of Hygiene and Tropical Medicine:

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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT03489018     History of Changes
Other Study ID Numbers: QA1075
First Posted: April 5, 2018    Key Record Dates
Last Update Posted: February 28, 2019
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data will be open access and held in the LSHTM data repository (http://datacompass.lshtm.ac.uk/cgi/request_doc?docid=1); Data access will be granted upon reasonable request after the primary analyses of the trial, as specified, are published.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: After the primary analyses of the trial are published
Access Criteria: Upon reasonable request with pre-specified hypothesis
URL: http://datacompass.lshtm.ac.uk/cgi/request_doc?docid=1

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by London School of Hygiene and Tropical Medicine:
Pneumococcal Vaccines;
Immunogenicity, Vaccine
10-valent pneumococcal vaccine
13-valent pneumococcal vaccine
Schedule
Pneumococcal Infection
Kenya
Infant
Vaccines, Conjugate
Humans
Immunization schedule
Streptococcus pneumoniae
vaccine
Dose-Response Relationship, immunologic
Equivalence Trial as Topic

Additional relevant MeSH terms:
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Streptococcal Infections
Infection
Communicable Diseases
Pneumonia
Pneumococcal Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs