Assessment of Viral Shedding in Children Previously in Receipt of Multiple Doses of Live Attenuated Influenza Vaccine (LAIV) Compared to Influenza Vaccine-naïve Controls

NCT03104790 | Completed Phase 4

• 1 other identifier: Flushed
• Study Type: interventional
• Target: 373
• Locations: 1 country
• Sites: 3

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. Understanding the relative importance of different factors over two seasons when the strain composition of the A/H1N1pdm09 LAIV virus will change and by comparing previously unvaccinated and highly vaccinated groups (with both LAIV and IIV), can potentially give unique insights into their contribution to the US LAIV observations. With the change of the A/H1N1pdm09 vaccine strain in 2017/18, demonstrating improved performance (in terms of VE, virus shedding and immunogenicity) and what contribution prior vaccination might make will be key evidence for both the UK, but also the US. Information presented at the ACIP in June 2018 from the 2016/17 and 2017/18 seasons will be key to inform US future decisions around use of LAIV. This is a parallel group, non randomised study which will enrol at least 400 children. Both written informed consent from parent/ guardian and written assent from the child will be in place prior to any study procedure. The two groups will be defined by previous influenza vaccination history, with around half the children naïve to any influenza vaccination (LAIV or IIV) and half having had at least three doses of LAIV with or without IIV. All will follow the same schedule of vaccination and oral fluid collection at day 0 (by the nurse in the home or at the GP surgery); nasal swab collection (by the parent at home on days 1,3,6); day 21 oral fluid collection (by nurse or parent at home or at GP surgery).

Conditions

Influenza Vaccination; Influenza; Vaccination

Outcome Measures

Primary Outcomes (1)

• virus shedding

  type-specific vaccine virus shedding and immunogenicity in 2017/18 and determine if there has been any change compared to previous studies in 2016/17 (conducted by this group, Eudract 2013-003592-35 and 2016-002352-24) following change in the A/H1N1pdm09 vaccine virus strain amongst children with the same prior vaccine history

  day 0, day 21

Study Arms (2)

naive

EXPERIMENTAL

Children who have never received any influenza vaccine (The two groups are defined by immunisation history, all receive the same intervention in the study)

Biological: Fluenz Tetra (The two groups are defined by immunisation history, all receive the same intervention in the study)

prior vaccinees

EXPERIMENTAL

Children who have received at least two doses of Fluenz Tetra previously (The two groups are defined by immunisation history, all receive the same intervention in the study)

Biological: Fluenz Tetra (The two groups are defined by immunisation history, all receive the same intervention in the study)

Interventions

Fluenz Tetra (The two groups are defined by immunisation history, all receive the same intervention in the study) BIOLOGICAL

live attenuated influenza vaccine (LAIV)

naive; prior vaccinees

Eligibility Criteria

• Age: 6 Years - 13 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Children age 6 to 13 years of age on enrolment and with either:
• Prior LAIV vaccination in at least 2 out of the 3 previous years
• Have never received LAIV or IIV in previous years
• Children eligible to receive LAIV in accordance with Green Book advice \[https://www.gov.uk/government/organisations/public-health-england/series/immunisation-against-infectious-disease-the-green-book\]
• Written informed consent given by parent/ guardian and assent from child (both must be in place to proceed)

You may not qualify if:

• Children may not be included in the study if any of the following apply:
• Admission to Paediatric ntensice care unit (PICU) for invasive ventilation due to a respiratory illness in the preceding 2 years.
• 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\*.
• \*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.
• 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
• Contraindications to vaccination on that occasion, e.g. due to child being acutely unwell:
• Febrile ≥38.0oC in last 72 hours
• \*\*Acute wheeze in last 72 hours requiring treatment beyond that normally prescribed for regular use by the child's treating healthcare professional
• \*\*Recent admission to hospital in last 2 weeks for acute asthma

Sponsors & Collaborators

• Public Health England: lead

Study Sites (3)

Gloucestershire primary care

Gloucester, Gloucestershire, United Kingdom

Location

Hertfordshire primary care

Hertford, Hertfordshire, United Kingdom

Location

Imperial Healthcare NHS Trust

London, United Kingdom

Location

Related Publications (1)

• Jackson D, Pitcher M, Hudson C, Andrews N, Southern J, Ellis J, Hoschler K, Pebody R, Turner PJ, Miller E, Zambon M. Viral Shedding in Recipients of Live Attenuated Influenza Vaccine in the 2016-2017 and 2017-2018 Influenza Seasons in the United Kingdom. Clin Infect Dis. 2020 Jun 10;70(12):2505-2513. doi: 10.1093/cid/ciz719.

  PMID: 31642899 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Elizabeth Coates, PhD

  Public Health England

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Two groups based on prior vaccination history

Study Record Dates

• First Submitted: March 23, 2017
• First Posted: April 7, 2017
• Study Start: October 2, 2017
• Primary Completion: March 13, 2018
• Study Completion: March 13, 2018
• Last Updated: August 28, 2019

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)