Assessment of Viral Shedding Week Following Administration of Live Attenuated Influenza Vaccine in Children (FluSHED-2)

• ClinicalTrials.gov Identifier: NCT03735147
• Recruitment Status: Completed
• First Posted: November 8, 2018
• Last Update Posted: July 8, 2019
• Sponsor: Imperial College London
• Collaborator: Public Health England
• Information provided by (Responsible Party): Imperial College London

Study Description

Brief Summary:

LAIV shedding studies in children could be an important way to confirm whether impediments to viral replication do indeed explain these observed reductions in vaccine effectiveness (VE), whether prior vaccination has any influence on replication and what future implications (if any) this might have for the UK paediatric LAIV programme. LAIV virus replication in children will be dependent on virological and host factors. The virus factors include replicative fitness of individual strains and the susceptibility to inhibition by other replicating strains (ability to compete). Host factors which may influence this include pre-existing specific immunity as a result of prior infection or previous vaccination (with either LAIV or IIV), and innate immune factors including mucosal immunity.

There is significant variability in shedding across viral subtypes in studies done to date, so there is a need to obtain local data in a small pilot observational study which will look in detail at virus shedding by sequential daily virus samples, something not possible on a larger scale. The data generated will inform future LAIV studies in the UK in terms of optimum time of sample collection for viral shedding studies, which are likely to be required on a regular basis, to supplement field studies of vaccine effectiveness.

This study will enrol up to 30 children that will allow these factors to be assessed. Both written informed consent from parent/ guardian and written assent from the child will be in place prior to any study procedure. All participants will have a baseline assessment of pre--existing influenza immunity (blood test, oral fluid collection and nasal swabs), followed by a single dose of LAIV. Parents will then be asked to take nasal swabs at home on days 1, 2, 3, 4, 5, 6, 7, 8, with further nasal swab, blood test and oral fluid collection in hospital 4 weeks later, in order to assess for immune responses to LAIV.

Condition or disease	Intervention/treatment	Phase
Influenza Vaccines	Biological: Live attenuated influenza vaccine (LAIV)	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Assessment of Viral Shedding Week Following Administration of Live Attenuated Influenza Vaccine in Children: FluSHED-2 Study
• Actual Study Start Date: October 23, 2018
• Actual Primary Completion Date: April 1, 2019
• Actual Study Completion Date: April 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: All children; Administration of live attenuated influenza vaccine (LAIV)	Biological: Live attenuated influenza vaccine (LAIV); Single dose of LAIV; Other Name: Fluenz Tetra

Outcome Measures

Primary Outcome Measures :

1. Kinetics of type-specific vaccine virus shedding in 2018/19 following LAIV administration (average shedding) [ Time Frame: 8 days post LAIV ]
   Kinetics of type-specific vaccine virus shedding in 2018/19 in the eight days following LAIV administration, assessed by Area under the curve (AUC) between days 0 and 8 calculated as average pfu/ml per day on logged data (with a minimum limit set at 1pfu (0 on the log scale))
2. Kinetics of type-specific vaccine virus shedding in 2018/19 following LAIV administration (peak day of shedding) [ Time Frame: 8 days post LAIV ]
   Kinetics of type-specific vaccine virus shedding in 2018/19 in the eight days following LAIV administration, assessed by day of peak shedding, for each individual strain
3. Kinetics of type-specific vaccine virus shedding in 2018/19 following LAIV administration (number of days of detectable shedding) [ Time Frame: 8 days post LAIV ]
   Kinetics of type-specific vaccine virus shedding in 2018/19 in the eight days following LAIV administration, assessed by the number of days of detectable shedding for each strain

Secondary Outcome Measures :

1. Quantitative analysis of immunogenicity: serological [ Time Frame: 1 month ]
   Haemagglutination inhibition (HAI) and Microneutralisation (MN) assay titres at each time point (day 0, 28) as well as ratios day 28/day 0 and proportions above thresholds and seroconverting
2. Quantitative analysis of immunogenicity: Oral fluids [ Time Frame: 1 month ]
   Haemagglutination inhibition (HAI) titres in oral fluids at each time point (day 0, 28)
3. Quantitative analysis of immunogenicity: nasal IgA [ Time Frame: 1 month ]
   Influenza-specific nasal IgA titres at each time point (day 0, 28)

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 16 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Children age 6 years to 15 years +364 days of age on enrolment
• Children eligible to receive LAIV in accordance with current UK vaccine policy
• Written informed consent given by parent/ guardian and assent from child

Exclusion Criteria:

Contraindications to LAIV (notwithstanding allergy to egg protein), which include:

• Hypersensitivity to the active ingredients, gelatin or gentamicin (a possible trace residue)
• Previous systemic allergic reaction to LAIV
• Previous allergic reaction to an influenza vaccine (not LAIV) is a relative contra-indication, which must be discussed with the CI to confirm patient suitability
• Children/adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids*.
• Children / adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection.

• Pregnancy (determined by history). Where this cannot be confirmed, a urine pregnancy test will be performed.

  • High---dose steroids is defined as a treatment course for at least one month, equivalent to a dose greater than 20mg prednisolone per day (any age), or for children under 20kg, a dose greater than 1mg/kg/day.

NB: LAIV is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled/low-dose oral systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.

Contacts and Locations

Locations

United Kingdom

Imperial College Healthcare NHS Trust (St. Mary's Hospital)

London, United Kingdom

Sponsors and Collaborators

Imperial College London

Public Health England

Investigators

• Principal Investigator: Paul J Turner, FRACP; Imperial College London

More Information

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT03735147
• Other Study ID Numbers: 18SM4658; 2018-002470-42 ( EudraCT Number ); 18/LO/1317 ( Other Identifier: NHS HRA )
• First Posted: November 8, 2018
• Last Update Posted: July 8, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases