Condition category
Infections and Infestations
Date applied
08/10/2019
Date assigned
28/11/2019
Last edited
28/11/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Global control of pneumococcal disease is limited by the cost of pneumococcal conjugate vaccines (PCV). In 2009, The Gambia introduced PCV using a routine three-dose schedule without a booster dose (a ‘3+0’ schedule). The introduction of PCV has led to large reductions in invasive pneumococcal disease due to serotypes included in the vaccine and severe pneumonia. Now that vaccine-type invasive pneumococcal disease is controlled, the Pneumococcal Vaccine Schedules (PVS) study will compare the ongoing use of the 3+0 schedule with transition to an alternative two-dose schedule that includes a booster dose one early dose and one booster dose. This proposed PVS sub-study aims to evaluate the effect of the booster dose on nasopharyngeal pneumococcal acquisition, the immunogenicity of the two schedules, and the co-administration of PCV with Yellow Fever vaccine.

Who can participate?
Infants aged 0-6 weeks resident in the PVS-AcqImm study area

What does the study involve?
PCV13 will be administered through the structures of the national immunisation programme with delivery of each schedule in two groups of 14 clusters. Sub-study participants in the alternative schedule clusters will be further allocated to two groups, one receiving co-administered PCV13 and Yellow Fever vaccine and one receiving PCV13 and Yellow Fever vaccine separated by one month. The researchers will measure the rate of pneumococcal nasopharyngeal acquisition in the 5 months after administration of the PCV13 booster dose. They will also measure pneumococcal antibody concentrations at 18 months of age and the proportion of children with protective Yellow Fever antibody levels one month after administration of Yellow Fever vaccine.

What are the possible benefits and risks of participating?
The possible benefits are enhanced clinical care for participants and the potential future benefits for the population of reduced numbers of immunization injections and a more sustainable EPI. The possible risks of participating are that the risk of pneumococcal disease may be different in the two groups. Both immunization schedules will provide significant protection against vaccine-type pneumococcal disease. It is difficult to estimate the magnitude of this potential risk, but it is very small and in the order of one excess case of vaccine-type disease during the course of the study.

Where is the study run from?
This is a collaborative study between the Gambia Government Ministry of Health and the Medical Research Council Unit, The Gambia at London School of Hygiene & Tropical Medicine (UK)

When is the study starting and how long is it expected to run for?
January 2018 to June 2022

Who is funding the study?
1. Bill and Melinda Gates Foundation
2. Mucosal Pathogens Research Unit, National Institutes of Health Research (UK)
3. Medical Research Council
4. Wellcome Trust
5. UKAID

Who is the main contact?
Dr Grant Mackenzie
gmackenzie@mrc.gm

Trial website

Contact information

Type

Scientific

Primary contact

Dr Grant Mackenzie

ORCID ID

http://orcid.org/0000-0002-4994-2627

Contact details

MRCG at LSHTM Field Station
Basse
273
Gambia
+220 (0)7207826
gmackenzie@mrc.gm

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

17683

Study information

Scientific title

The effect of a two-dose compared to a three-dose schedule of pneumococcal conjugate vaccine on pneumococcal acquisition, immunogenicity, and co-administration of pneumococcal conjugate and yellow fever vaccines

Acronym

PVS-AcqImm

Study hypothesis

The hypothesis of the acquisition sub-study is that the PCV13 booster dose at 9 months of age in the 1+1 schedule reduces acquisition of VT pneumococci compared to the 3+0 schedule. The hypotheses of the immunogenicity/co-administration sub-study are that VT specific IgG responses are superior at 18 months of age following administration of the PCV13 booster dose at 9 months of age in the 1+1 schedule compared to the 3+0 schedule and that immune responses to YF vaccine are non-inferior when administered with compared to separately from PCV13.

Ethics approval

1. Approved 14/08/2019, Gambia Government/Medical Research Council Unit Joint Ethics Committee (MRC Unit The Gambia at LSHTM, Fajara, PO Box 273 Banjul, The Gambia; Tel: +220 (0)4495442 ext. 2308; Email: ethics@mrc.gm), ref: 17683
2. Approved 20/08/2019, London School of Hygiene & Tropical Medicine Interventions Research Ethics Committee (Keppel St, London, WC1E 7HT, UK; Tel: +44 (0)20 76368636, Email: ethics@lshtm.ac.uk), ref: 17683

Study design

Phase IV parallel unmasked cluster-randomised trial

Primary study design

Interventional

Secondary study design

Cluster randomised trial

Trial setting

Community

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Pneumococcal acquisition and vaccine immunogenicity

Intervention

13-valent pneumococcal conjugate vaccine (PCV13) is a licenced product, procured by the Gambia Government EPI, delivered in two schedules, one with doses scheduled at ages 6, 10 and 14 weeks (3+0 schedule) and the other with doses scheduled at ages 6 weeks and 9 months (1+1 schedule). In one arm of this substudy, PCV13 will be given at 9 months of age and YF vaccine at 10 months of age. YF vaccine is a licenced product procured by the Gambia Government EPI. Participants will be selected from the 28 clusters closest to Basse. Thus, individual participants in this acquisition/immunogenicity sub-study will not be individually randomised as their group allocation will be determined by their village of residence and cluster allocation in the larger PVS trial. Of these 28 clusters, 14 are allocated to each of the 1+1 and 3+0 groups, four of these 28 clusters include health facilities (two in the 1+1 group), and 14 are stratified as high clinical pneumonia incidence (seven in the 1+1 group).

Intervention type

Biological/Vaccine

Phase

Phase IV

Drug names

13-valent pneumococcal conjugate vaccine (PCV13); Yellow fever vaccine

Primary outcome measure

1. Nasopharyngeal acquisition of vaccine-type pneumococci measured using latex sweep serotyping at five timepoints between 9 and 14 months of age
2. Concentration of pneumococcal vaccine-type serotype-specific IgG measured by enzyme-linked immunosorbent assay at 18 months of age
3. Yellow fever neutralizing antibody titre expressed as the serum dilution that yields neutralisation of greater than or equal to 50% of virus infections of a standard cell line, measured 1 month after administration of yellow fever vaccine

Secondary outcome measures

1. Rate of non-vaccine type pneumococcal nasopharyngeal acquisition between 9 and 14 months of age
2. Proportion with vaccine-type pneumococcal colonisation at 6, 9 and 18 months of age
3. Proportion with geometric mean concentration of pneumococcal vaccine-type serotype-specific IgG ≥0.35 µg/ml, 4 weeks after the primary series and 4 weeks after the booster dose at age 9 months, and at 18 months of age
4. Pneumococcal vaccine-type opsonophagocytic antibody titres following a single dose of PCV13 at age 6 weeks, following three primary doses, following the booster dose at age 9 months, and at 18 months of age
5. Geometric mean concentrations of pneumococcal vaccine-type serotype-specific IgG 4 weeks after administration of PCV13 at 9 months of age with and without co-administration with yellow fever vaccine

Overall trial start date

11/01/2018

Overall trial end date

30/06/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Resident in the study area (PVS-AcqImm trial)
2. Age 0-6 weeks
3. Intention to reside in cluster until 18 months of age

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

784 infants enrolled in PVS will be evaluated for pneumococcal acquisition, and 336 of these infants will also be evaluated for immunogenicity and PCV co-administration with yellow fever vaccine

Participant exclusion criteria

1. Intent to move out of the study area before 18 months of age
2. Age greater than 6 weeks
3. Prematurity <34 weeks gestation
4. Birth weight <2.0kg or weight <2.5 kg
5. History of invasive bacterial infection or measles
6. Receiving long-term antibiotic therapy, defined as greater than 4 weeks
7. HIV infection in the infant or mother
8. Chronic debilitating illness
9. Immunosuppressive therapy or immunodeficiency disorder
10. Contraindication to PCV13 – severe hypersensitivity to a previous dose of PCV13
11. Contraindication to YF vaccine

Recruitment start date

01/12/2020

Recruitment end date

31/01/2022

Locations

Countries of recruitment

Gambia

Trial participating centre

MRC Unit, The Gambia at LSHTM
Basse Field Station
Basse
273
Gambia

Sponsor information

Organisation

London School of Hygiene & Tropical Medicine

Sponsor details

Keppel St
London
WC1E 7HT
United Kingdom
+44 (0)2076368636
rgio@lshtm.ac.uk

Sponsor type

University/education

Website

http://lshtm.ac.uk

Funders

Funder type

Charity

Funder name

Bill and Melinda Gates Foundation

Alternative name(s)

Bill & Melinda Gates Foundation, BMGF

Funding Body Type

private sector organisation

Funding Body Subtype

Trusts, charities, foundations (both publically funded and privately funded)

Location

United States of America

Funder name

Mucosal Pathogens Research Unit, National Institutes of Health Research (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Funder name

Wellcome Trust

Alternative name(s)

Wellcome, WT

Funding Body Type

private sector organisation

Funding Body Subtype

international

Location

United Kingdom

Funder name

UKAID

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The researchers plan to publish the results of the pneumococcal acquisition measurements at the end of 2022 and the results of the pneumococcal and yellow fever antibody results in the middle of 2023. Additional study documents are not yet available. The study protocol and statistical analysis plan will be published before the close of recruitment and uploaded on the ISRCTN study record.

IPD sharing statement
The datasets generated during and/or analysed during the current study will be available upon request from MRC Unit The Gambia at LSHTM (archives@mrc.gm). Data will be available indefinitely after all study publications have been accepted although earlier requests will be considered on a case by case basis, data requests will be reviewed by the MRC Unit The Gambia at LSHTM Scientific Coordinating Committee and the Gambia Government/MRC Joint Ethics Committee, consent from participants has been obtained for data sharing, data will be anonymised.

Intention to publish date

31/12/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

31/10/2019: Trial's existence confirmed by ethics committee.