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 :
Active, not recruiting
First Posted : November 21, 2018
Last Update Posted : November 7, 2023
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Tracking Information | |||||||||||||||||
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First Submitted Date ICMJE | March 29, 2018 | ||||||||||||||||
First Posted Date ICMJE | November 21, 2018 | ||||||||||||||||
Last Update Posted Date | November 7, 2023 | ||||||||||||||||
Actual Study Start Date ICMJE | March 21, 2019 | ||||||||||||||||
Actual Primary Completion Date | September 30, 2022 (Final data collection date for primary outcome measure) | ||||||||||||||||
Current Primary Outcome Measures ICMJE |
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
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Original Primary Outcome Measures ICMJE |
Immunogenicity: the proportion of children who 'seroconvert' to vaccine-serotypes after vaccination [ Time Frame: 4-weeks post-boost (approximately 10 months of age) ] The proportion of children with vaccine-serotype specific IgG antibody concentrations more than or equal to 0.35 mcg/ml after vaccination
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures |
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Descriptive Information | |||||||||||||||||
Brief Title ICMJE | The Effect of Fractional Doses of Pneumococcal Conjugate Vaccines on Immunogenicity and Carriage in Kenyan Infants | ||||||||||||||||
Official Title ICMJE | The Effect of Fractional Doses of Pneumococcal Conjugate Vaccines (PCV10 and PCV13) on Immunogenicity and Vaccine-serotype Carriage in Kenyan Infants | ||||||||||||||||
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. |
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Detailed Description | Background: PCV is currently the most expensive vaccine in the routine immunisation schedule in Gavi-supported countries. This study aims to provide evidence which may enable a substantial decrease in the cost of PCV programmes, therefore increasing the sustainability of PCV programmes in low and middle income countries (LMICs). We propose to assess whether fractional (20% and 40%) doses of pneumococcal conjugate vaccine (PCV10 and PCV13) in a 2p+1 schedule (2 primary doses followed by a booster dose) induce non-inferior immunogenicity and effects on vaccine-serotype carriage when compared to the full dose. These lower doses could convert new 4-dose vials of PCVs into 10- or 20-dose vials, ready for immediate implementation in LMIC programmes. Primary objective: Non-inferior immunogenicity at 1-month post-boost (10 months of age). Non-inferiority will be reached if the lower CI around the ratio of geometric mean concentrations (GMC) of IgG (fractional/full dose) is >0.5 (i.e. the 2-fold criterion). Secondary objectives: Non-inferior immunogenicity at 1-month post-primary series (18 weeks of age). Non-inferiority will be achieved if the lower limit of the 95% confidence interval (CI) around the difference in the proportion of 'responders', children with IgG>=0.35 mcg/ml, (fractional dose group - full dose group) is >-10% for at least 8 of the 10 vaccine types in the PCV10 arms and at least 10 of the 13 vaccine types in the PCV13 arms. The opsonophagocytic activity of the antibody response to 7 serotypes after full/ fractional doses at the 1-month post-boost time point. The direct vaccine effectiveness of full/fractional doses of PCV13 against carriage of serotypes 6A and 19A, with primary analyses at 18 months of age and secondary analyses at 9 months of age. The proportion of children with evidence of vaccine-serotype carriage by trial arm at 9 and 18 months of age. The geometric mean concentration (GMC) of serotype-specific IgG after the primary series of the 2p+1 schedule, prior to boost, at 9 months of age. The geometric mean concentration (GMC) of serotype-specific IgG after three doses of vaccine in a 2p+1 schedule at 18 months of age. The carriage prevalence at 9 and 18 months of age and IgG concentrations at 4 weeks after the primary series after full dose of PCV10 in a 3p+0 schedule, and full/ fractional doses of PCV10/13 in a 2p+1 schedule. Trial design: A phase IV individually-randomised controlled trial of full or fractional (20% or 40%) doses of PCV10/ PCV13, given as a 3-dose schedule to infants: 2 doses at 6 and 14 weeks of age and a booster dose at 9 months (the 2p+1 schedule) or 3 full doses at 6, 10 and 14 weeks of age (the 3p+0 schedule). At 6-8 weeks of age, 300 infants will be enrolled at random into each of the seven trial arms and followed until 18 months of age. The seven trial arms: 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. This arm would represent the current vaccine and schedule in the Kenyan routine immunisation programme and would act as an additional comparison arm. Study procedures: No study procedures will be conducted without prior parental informed consent. Participants in trial arms A-F will provide 3 or 5 blood samples in the course of the trial at enrolment, 4 weeks post-primary series (approximately 18 weeks of age) and 4 weeks post-boost (approximately 10 months of age); additionally a random selection of half the participants will contribute blood samples pre-boost (9 months of age) and at the last study visit (18 months of age). Participants in trial arm G will provide 2 blood samples (at enrolment and at 4 weeks post-primary series (approximately 18 weeks of age). All participants will provide 2 nasopharyngeal swabs at approximately 9 and 18 months of age and contribute safety data. |
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Study Type ICMJE | Interventional | ||||||||||||||||
Study Phase ICMJE | Phase 4 | ||||||||||||||||
Study Design ICMJE | 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 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
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||||
Recruitment Status ICMJE | Active, not recruiting | ||||||||||||||||
Actual Enrollment ICMJE |
2100 | ||||||||||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||||||||||
Estimated Study Completion Date ICMJE | December 30, 2024 | ||||||||||||||||
Actual Primary Completion Date | September 30, 2022 (Final data collection date for primary outcome measure) | ||||||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 6 Weeks to 8 Weeks (Child) | ||||||||||||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||||||||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||||||||||||
Listed Location Countries ICMJE | Kenya | ||||||||||||||||
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Administrative Information | |||||||||||||||||
NCT Number ICMJE | NCT03489018 | ||||||||||||||||
Other Study ID Numbers ICMJE | QA1075 | ||||||||||||||||
Has Data Monitoring Committee | Yes | ||||||||||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | London School of Hygiene and Tropical Medicine | ||||||||||||||||
Original Responsible Party | Same as current | ||||||||||||||||
Current Study Sponsor ICMJE | London School of Hygiene and Tropical Medicine | ||||||||||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | London School of Hygiene and Tropical Medicine | ||||||||||||||||
Verification Date | March 2023 | ||||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |