Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202105670402672 Date of Approval: 06/05/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Pneumococcal Vaccine Schedules Acquisition-Immunogenicity
Official 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
Brief summary describing the background and objectives of the trial 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.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) PVS AcqImm
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Pneumococcal acquisition and vaccine immunogenicity
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/07/2020
Actual trial start date 14/09/2020
Anticipated date of last follow up 14/07/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 784
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
SCC 1670 MRCG at LSHTM Scientific Coordinating Committee
LSHTM EC Ref 17683 LSHTM Ethics Committee
72821613 ISRCTN
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group 13 valent pneumococcal conjugate vaccine 3 36 months 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) 392 Dose Comparison
Experimental Group Pneumococcal conjugate vaccine 2 36months 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. 392
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Resident in the study area Age 0-10 weeks Intention to reside in cluster until 18 months of age Intent to move out of the study area before 18 months of age Age greater than 10 weeks Prematurity <34 weeks gestation Birth weight <2.0kg or weight <2.5 kg History of invasive bacterial infection or measles Receiving long-term antibiotic therapy, i.e. greater than 4 weeks HIV infection in the infant or mother Chronic debilitating illness Immunosuppressive therapy or immunodeficiency disorder Contraindication to PCV13 – severe hypersensitivity to a previous dose of PCV13 Contraindication to YF vaccine New born: 0 Day-1 Month 0 Week(s) 10 Week(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/08/2019 Gambia Government and Medical Research Council Unit Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Atlantic Blvd Fajara 273 Gambia
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 20/08/2019 London School of Hygiene and Tropical Medicine
Ethics Committee Address
Street address City Postal code Country
Keppel Street London WC1E 7HT United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 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 between 9 and 14 months, 18 months and 1 month after administration of yellow fever vaccine
Secondary Outcome 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 6, between 9 and14, and 18 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Basse Field Station Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine N/A Basse Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation N/A Seattle Washington United States of America
Medical research Council Uk N/A London United Kingdom
Wellcome Trust N/A London United Kingdom
Mucosal Pathogens Research Unit University College London Gower Street London United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor London School of Hygiene and Tropical Medicine Keppel Street London United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Gambia Government Expanded Programme on Immunisation Bertil Harding Highway Kotu Gambia
London School of Hygiene and Tropical Medicine Keppel Street London United Kingdom
Murdoch Childrens Research Institute New Vaccines Group Flemington Road Melbourne Australia
Berhard Nocht Institute for Tropical Medicine Bernhard Nocht Hamburg Germany
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Grant Mackenzie gmackenzie@mrc.gm 002207207826 N/A
City Postal code Country Position/Affiliation
Basse Gambia Clinical Epidemiologist Paediatrician at MRCG at LSHTM
Role Name Email Phone Street address
Public Enquiries Jama Jack jjack@mrc.gm 002204495442 Atlantic Road
City Postal code Country Position/Affiliation
Fajara Gambia Head of Communications MRCG at LSHTM
Role Name Email Phone Street address
Scientific Enquiries Grant Mackenzie gmackenzie@mrc.gm 002207207826 N/A
City Postal code Country Position/Affiliation
Basse Gambia Clinical Epidemiologist Paediatrician at MRCG at LSHTM
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The data generated within the study will be suitable for sharing in an anonymised format. The data will be in CDISC ODM format that is an internationally recognized standard suitable to share with other interested researchers Study Protocol The datasets collected within the trial will be available to other users once all relevant trial related publications in scientific journals have been accepted. Prior to this point requests will be considered on a case by case basis. For practical reasons this time period may be indicative and might need to be revised if delays occur. Different periods may be applied to different datasets, e.g. to take account complexity of cleaning and documentation. Timing will depend on the trial‟s collection patterns. In relation to timing, the terms could, for instance, be expressed as follows: “6-months after the end of the current grant period”, “12-months after new data collection to allow for data cleaning and documentation” or “3-months following the first publication of findings based on the data.” Requests for access to the complete datasets will need to be made to the Unit's Archives department who will then forward it to the Scientific Coordinating Committee (SCC) of the Unit. All requests for the dataset will be reviewed by the SCC and also by The Gambia Government/MRC Joint Ethics Committee to establish that the request is in order to perform scientifically appropriate analysis
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information