NCT02972957

Brief Summary

The live attenuated influenza vaccine (LAIV) is made up of weakened influenza viruses given into the nose and in early studies was shown to be better than the standard influenza vaccine at preventing infections in children. However, more recently, it has performed less well and it may also work less well in Sub-Saharan Africa. Not only do the investigators not know why this is, but the investigators also do not fully understand why LAIV produces stronger nasal antibody responses in some individuals but not others. Usually harmless bacteria that are present in participants noses can influence how our immune system works and variations in these may explain differences in how LAIV works. The project will recruit children given LAIV in the Gambia to gain further understanding of these issues. The investigators will measure a variety of responses to LAIV, including genes that can change their expression early after vaccination and use advanced computational techniques to identify new relationships between these genes and other LAIV responses. The investigators will also see whether nasal bacterial profiles in children who respond to LAIV are different from those who do not. In addition, the investigators will alter these bacteria in a subset of children with antibiotics and see whether this affects both nasal gene expression and later responses to LAIV.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
364

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Jan 2017

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 17, 2016

Completed
8 days until next milestone

First Posted

Study publicly available on registry

November 25, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

January 30, 2017

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2018

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 23, 2019

Completed
Last Updated

February 21, 2020

Status Verified

February 1, 2020

Enrollment Period

1.9 years

First QC Date

November 17, 2016

Last Update Submit

February 20, 2020

Conditions

Influenza

Keywords

intranasalflu vaccineGambian children

Outcome Measures

Primary Outcomes (3)

  • nasal IgA response

    Influenza specific nasal IgA responses

    21 days post LAIV

  • fold increase in oral fluid influenza-specific/total IgA ratio

    day 0 - Day 21

  • fold increase in oral fluid influenza-specific/total IgG ratio

    Day 0 - Day 21

Secondary Outcomes (3)

  • density of S. Pneumoniae

    day 7 and day 21 after LAIV compared to day 0

  • Changes in the relative abundance of different operational taxanomic units (OTUs) of nasopharyngeal microbiota

    day 7 and day 21 compared to day 0 in each participant

  • gene expression changes in nasal and systemic samples

    2 days after LAIV

Study Arms (4)

LAIV-vaccinated group 1

EXPERIMENTAL

Nasovac-S vaccination group A , blood samples days 0, 2, 21

Biological: Nasovac-S

LAIV-vaccinated group 2

EXPERIMENTAL

Nasovac-S vaccination group B, blood samples at days 0, 7, 21

Biological: Nasovac-S

Unvaccinated

NO INTERVENTION

control group C

Oral Azithromycin & vaccination

EXPERIMENTAL

group D - a single dose of oral Azithromycin will be given 28 days prior to Nasovac-S vaccination

Biological: Nasovac-SDrug: Azithromycin

Interventions

Nasovac-SBIOLOGICAL

one of 0.5ml intranasal dose of trivalent live attenuated vaccine (LAIV)

LAIV-vaccinated group 1LAIV-vaccinated group 2Oral Azithromycin & vaccination
AzithromycinDRUG

a single dose of Azithromycin (liquid formulation - Zithromax) at 20mg/Kg (up to a maximum adult dose 1g) to be given to a subset of subjects

Also known as: Zithromax
Oral Azithromycin & vaccination

Eligibility Criteria

Age24 Months - 59 Months
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Healthy male or female child at least 24 months of age and less than 60 months of age at the time of study entry.
  • Resident in the study area and with no plans to travel outside the study area during the period of subject participation.
  • Informed consent for the study participation obtained from a parent (or guardian only if neither parent is alive or if guardianship has been legally transferred (see section 11.2).
  • Willingness and capacity to comply with the study protocol as judged by a member of the clinical trial team.

You may not qualify if:

  • Serious, active, medical condition, including but not limited to:
  • chronic disease of any body system
  • severe protein-energy malnutrition (weight-for-height Z-score of less than -3)
  • known genetic disorders, such as Down's syndrome or other cytogenetic disorder
  • Active wheezing
  • History of documented hypersensitivity to eggs or other components of the vaccine (including gelatin, sorbitol, lactalbumin and chicken protein), or with life-threatening reactions to previous influenza vaccinations.
  • History of documented hypersensitivity to macrolide antibiotics
  • History of Guillain-Barré syndrome.
  • Receipt of aspirin therapy or aspirin-containing therapy within the two weeks before planned study vaccination.
  • Any suspected or confirmed congenital or acquired state of immune deficiency including but not limited to primary immunodeficiencies including thymus disorders, HIV/AIDS, hematological or lymphoid malignancies (blood tests will not be routinely undertaken with this regard as part of the study).
  • The use of inhaled corticosteroids within the last one month.
  • Receipt of an influenza vaccine within the past 12 months.
  • Has any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the child or make it unlikely that the child would complete the study.
  • Any significant signs or symptoms of an acute illness or infection including:
  • an axillary temperature of 38.0°C or above or documented fever of 38°C or above in the preceding 14 days.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical Research Council unit The Gambia

Banjul, The Gambia

Location

Related Publications (5)

  • Peno C, Jagne YJ, Clerc M, Balcazar Lopez C, Armitage EP, Sallah H, Drammeh S, Senghore E, Goderski G, van Tol S, Meijer A, Ruiz-Rodriguez A, de Steenhuijsen Piters WAA, de Koff E, Jarju S, Lindsey BB, Camara J, Bah S, Mohammed NI, Kampmann B, Clarke E, Dockrell DH, de Silva TI, Bogaert D. Interactions between live attenuated influenza vaccine and nasopharyngeal microbiota among children aged 24-59 months in The Gambia: a phase 4, open-label, randomised controlled trial. Lancet Microbe. 2025 Mar;6(3):100971. doi: 10.1016/j.lanmic.2024.100971. Epub 2025 Jan 17.

    PMID: 39832517DERIVED

  • Keeley AJ, Groves D, Armitage EP, Senghore E, Jagne YJ, Sallah HJ, Drammeh S, Angyal A, Hornsby H, de Crombrugghe G, Smeesters PR, Rossi O, Carducci M, Peno C, Bogaert D, Kampmann B, Marks M, Shaw HA, Turner CR, de Silva TI. Streptococcus pyogenes Colonization in Children Aged 24-59 Months in the Gambia: Impact of Live Attenuated Influenza Vaccine and Associated Serological Responses. J Infect Dis. 2023 Oct 3;228(7):957-965. doi: 10.1093/infdis/jiad153.

    PMID: 37246259DERIVED

  • Peno C, Armitage EP, Clerc M, Balcazar Lopez C, Jagne YJ, Drammeh S, Jarju S, Sallah H, Senghore E, Lindsey BB, Camara J, Bah S, Mohammed NI, Dockrell DH, Kampmann B, Clarke E, Bogaert D, de Silva TI. The effect of live attenuated influenza vaccine on pneumococcal colonisation densities among children aged 24-59 months in The Gambia: a phase 4, open label, randomised, controlled trial. Lancet Microbe. 2021 Dec;2(12):e656-e665. doi: 10.1016/S2666-5247(21)00179-8.

    PMID: 34881370DERIVED

  • Lindsey BB, Jagne YJ, Armitage EP, Singanayagam A, Sallah HJ, Drammeh S, Senghore E, Mohammed NI, Jeffries D, Hoschler K, Tregoning JS, Meijer A, Clarke E, Dong T, Barclay W, Kampmann B, de Silva TI. Effect of a Russian-backbone live-attenuated influenza vaccine with an updated pandemic H1N1 strain on shedding and immunogenicity among children in The Gambia: an open-label, observational, phase 4 study. Lancet Respir Med. 2019 Aug;7(8):665-676. doi: 10.1016/S2213-2600(19)30086-4. Epub 2019 Jun 21.

    PMID: 31235405DERIVED

  • Armitage EP, Camara J, Bah S, Forster AS, Clarke E, Kampmann B, de Silva TI. Acceptability of intranasal live attenuated influenza vaccine, influenza knowledge and vaccine intent in The Gambia. Vaccine. 2018 Mar 20;36(13):1772-1780. doi: 10.1016/j.vaccine.2018.02.037. Epub 2018 Feb 23.

    PMID: 29483030DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Respiratory Tract InfectionsInfectionsOrthomyxoviridae InfectionsRNA Virus InfectionsVirus DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 17, 2016

First Posted

November 25, 2016

Study Start

January 30, 2017

Primary Completion

December 19, 2018

Study Completion

May 23, 2019

Last Updated

February 21, 2020

Record last verified: 2020-02

Data Sharing

IPD Sharing
Will not share

Locations

TH(1)