Condition category
Infections and Infestations
Date applied
12/03/2019
Date assigned
01/04/2019
Last edited
26/03/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Infectious diseases remain very common in low-income countries. Vaccines protect people against infectious diseases, but several important vaccines do not work as well in low-income countries compared to high-income countries. BCG is the only licensed vaccine for prevention of tuberculosis. It is given at birth in countries where tuberculosis is common and works well at preventing tuberculosis in childhood, but less well at preventing tuberculosis later in life. However, it is thought that BCG may have other effects unrelated to tuberculosis (so called “non-specific” effects”). One of these is that BCG might improve how someone responds to other unrelated vaccinations. This study aims to investigate whether giving BCG beforehand will improve the immune response to unrelated vaccines.

Who can participate?
Healthy volunteer children (aged 13-17, with no gender restriction) who are participating in the Entebbe Mother and Baby Study.

What does the study involve?
Children will be randomly allocated to receive either BCG re-vaccination or no BCG re-vaccination. Four weeks later, they will be vaccinated against yellow fever and typhoid, and against Human Papilloma Virus (which can cause cancer of the cervix [or opening] of the womb, and other cancers). Later (at 28 weeks from enrolment into the study) they will receive a booster vaccine against tetanus and diphtheria. Four weeks after receiving each of these vaccinations (eight weeks after receiving BCG), their immune responses to each vaccine will be measured.

What are the possible benefits and risks of participating?
Participants will benefit from receiving the vaccines as they are expected to provide protection against infectious diseases. Participants and their families will benefit from improved understanding of vaccines. No major risks to the participants are anticipated since all the vaccines to be given are licensed and known to be safe. The main risk to participants will be time lost from school work, and we will work with parents to minimise this. Very rarely, a vaccine may cause a severe allergic reaction, so individuals who have previously suffered a possible allergic reaction to vaccines or their components will not be included in the study.

Where is the study run from?
The host institution for the study will be the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit (MRC/UVRI & LSHTM), Entebbe, Uganda.

When is the study starting and how long is it expected to run for?
May 2019 to May 2021

Who is funding the study?
The study is funded by the UK Medical Research Council.

Who is the main contact?
Professor Alison Elliott, alison.elliott@lshtm.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Emily Webb

ORCID ID

http://orcid.org/0000-0002-4019-7456

Contact details

London School of Hygiene and Tropical Medicine
Keppel St
London
WC1E 7HT
United Kingdom
+44(0)207 9272012
emily.webb@lshtm.ac.uk

Type

Scientific

Additional contact

Prof Alison Elliott

ORCID ID

Contact details

MRC/UVRI and LSHTM Uganda Research Unit
Entebbe
UVRI P.O.Box 49
Uganda
+44(0)207 6368636
alison.elliott@mrcuganda.org

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

v1

Study information

Scientific title

Population differences in vaccine response: the role, reversibility and mediators of immunomodulation by chronic infections in the tropics (POPVAC). Trial protocol C: The impact of BCG “pre-immunisation” on the response to vaccines among Ugandan adolescents participating in the Entebbe Mother and Baby Study

Acronym

POPVAC C

Study hypothesis

BCG “pre-immunisation” modifies the response to subsequent vaccines

Ethics approval

1. Approved 05/09/2018, UVRI REC (The REC secretariat, Uganda Virus Research Institute, P.O Box 49, Entebbe, Uganda; +245 (0)414321962; directoruvri@uvri.go.ug), ref: GC/127/18/09/682
2. Awaiting approval, LSHTM Ethics (LSHTM, Keppel St, London WC1E 7HT; ethics@lshtm.ac.uk; +44 (0)207 6368636)
3. Awaiting approval, UNCST ethics (Plot 6, Kimera Road, Ntinda, P.O. Box 6884, Kampala, Uganda; +256 (0)414 705500; info@uncst.go.ug)
4. Awaiting approval, NDA (Secretariat office Kampala, Plot 19 Lumumba Avenue, P.O. Box 23096, Kampala, Uganda; +245 (0) 417 788 100; ndaug@nda.or.ug)

Study design

A single-centre individually randomised controlled open parallel group trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Community

Trial type

Other

Patient information sheet

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

Condition

Vaccine responses

Intervention

A randomisation code will be generated by the trial statistician using a randomly permuted block size. Participants will be allocated in a 1:1 ratio to receive either BCG pre-immunisation or no BCG pre-immunisation. Participants in the pre-immunisation arm will receive BCG vaccination (0.1 ml in the deltoid region of the right upper arm) four weeks before receiving a panel of other, unrelated, vaccines. Participants in the non BCG pre-immunisation arm will receive no BCG prior to receiving the other vaccines.

Blood, urine and stool samples will be collected from participants in order to determine the impact of the intervention on primary and secondary outcomes. Other characteristics will be determined by questionnaire and clinical examination.

Intervention type

Biological/Vaccine

Phase

Not Applicable

Drug names

Primary outcome measure

1. BCG: BCG-specific IFN-gamma ELIspot response eight weeks post BCG immunisation
2. YF-17D: neutralising antibody titres (plaque-reduction neutralisation test) at four weeks post YF immunisation
3. Ty21a: Salmonella typhi lipopolysaccharide (LPS)-specific immunoglobulin(Ig)G concentration at four weeks post Ty21a immunisation
4. HPV: IgG specific for L1-proteins of HPV-16/18 at four weeks post HPV priming immunisation
5. Td: tetanus and diphtheria toxoid-specific IgG concentration at four weeks post Td immunisation

Secondary outcome measures

1. Protective immunity. Proportions with protective neutralising antibody (YF); protective IgG levels (TT); seroconversion rates (Ty21a) at four weeks post the corresponding immunisation.
2. Response waning. Primary outcome measures (all vaccines) repeated at week 52, and area-under-the curve (AUC) analyses.
3. Priming versus boosting. Effects on priming versus boosting will be examined for HPV only, comparing outcomes four weeks after the first, and four weeks after the second vaccine dose.

Overall trial start date

01/05/2018

Overall trial end date

30/04/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Participants must meet all of the following criteria to enter the trial:
1. A participant in the Entebbe Mother and Baby Study. Participants will be aged 13-17 years of age.
2. Written informed consent by parent or guardian
3. Written informed assent by participant
4. Willing to remain in the study area for the duration of the study
5. Willing to provide locator information and to be contacted during the course of the trial
6. Agree to avoid pregnancy for the duration of the trial (female only)
7. Able and willing (in the investigator's opinion) to comply with all the study requirements

Participant type

Healthy volunteer

Age group

Child

Gender

Both

Target number of participants

900

Participant exclusion criteria

1. Concurrent enrolment into another clinical trial. Of note, EMaBS participants enrolled into trial TB042 “Open label, dose escalation and age de-escalation for ChAdOx1 85A in Ugandan adults and adolescents, followed by a Phase IIa randomised, open-label trial among adolescents comparing ChAdOx1 85A prime followed by MVA85A boost versus BCG re-vaccination” will not be eligible to enrol into this study. If they have not already received the vaccines offered in this study, they will be given the opportunity to receive them, as a service (not as part of a study) once TB042 follow up has been completed.
2. Clinically significant history of immunodeficiency (including HIV), cancer, cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness
3. History of serious psychiatric condition or disorder
4. Previous immunisation with YF, oral typhoid or HPV vaccine; previous immunisation with BCG or Td at age >5 years
5. Concurrent oral or systemic steroid medication or the concurrent use of other
immunosuppressive agents within 2 months prior to enrolment
6. History of allergic reaction to immunisation or any allergy likely to be exacerbated by any
component of the study vaccines including egg or chicken proteins
7. Tendency to develop keloid scars
8. Positive HIV serology
9. Positive pregnancy test
10. Female currently lactating, confirmed pregnancy or intention to become pregnant during the trial period
11. Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccines for 30 days prior to dosing with the study vaccine, or planned use during the study period
12. Administration of immunoglobulins and/or any blood products within the three months
preceding the planned trial immunisation date

Recruitment start date

01/06/2019

Recruitment end date

31/03/2021

Locations

Countries of recruitment

Uganda

Trial participating centre

MRC/UVRI and LSHTM Uganda Research Unit
Plot 51-59 Nakiwogo Road
Entebbe
NA
Uganda

Sponsor information

Organisation

London School of Hygiene and Tropical Medicine

Sponsor details

Keppel St
London
WC1E 7HT
United Kingdom
+44(0)207 636 8636
postmaster@lshtm.ac.uk

Sponsor type

University/education

Website

http://www.lshtm.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council

Alternative name(s)

MRC

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

We plan to publish the study protocol on around 01/12/2019. We would then plan to publish the results of the trial in a high-impact peer-reviewed journal with an intention to publish date of 30/04/2023.

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

30/04/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

26/03/2019: Trial’s existence confirmed by funder.