Efficacy & Safety of Nasal Influenza Immunisation in Children

Study Overview
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Brief Summary
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The UK Departments of Health now recommend annual influenza vaccination for all children 2-7 years of age, with children over 7 years eligible for vaccination if in certain higher risk clinical categories. Though data are available documenting the safety and immunogenicity of LAIV in this age group, there are little data to assess efficacy and immune correlates in UK children, and in particular atopic children. This study will enrol 200 children (and at least 200 unvaccinated household sibling controls), many with a history of asthma or recurrent wheezing, and allow an assessment of efficacy, safety and immune correlates in these children, and how this varies with prior administration of pandemic influenza vaccine and/or LAIV.

Official Title
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Efficacy & Safety of Nasal Influenza Immunisation in Children - The SNIFFLE-3 Study

Conditions
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Influenza Vaccines Efficacy and Safety

Intervention / Treatment
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* Drug: Live attenuated influenza vaccine
* Procedure: Surveillance (nasal swabbing) during influenza season


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 2 - 18 years old Written informed consent from parent/guardian (or patient themselves from age 16 years), with assent from children aged 8 years and above wherever possible. Exclusion Criteria: Hypersensitivity to the active ingredients, gelatin or gentamicin (a possible trace residue) [notwithstanding allergy to egg protein] 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 site PI 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 of prednisolone at 20mg or more per day (any age); or for children under 20kg, a dose of 1mg/kg/day or more. Children and 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 Febrile ≥ 38.0 'C 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 Current oral steroid for asthma exacerbation or course completed within last 2 weeks Received any blood or blood products within the past 12 weeks Any other significant condition or circumstance which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Administration of Live attenuated influenza vaccine (LAIV) as per national guidance. Surveillance thereafter through nasal swabbing in the event of influenza-like illness. | Drug: Live attenuated influenza vaccine<br>* Administration of LAIV, with subsequent surveillance (nasal swabbing) during influenza season<br>* Other names: Flumist;Procedure: Surveillance (nasal swabbing) during influenza season<br> <br> |
| Other: Controls<br>Surveillance in siblings of participants in the Intervention arm, through nasal swabbing in the event of influenza-like illness, irrespective of their vaccination status. | Procedure: Surveillance (nasal swabbing) during influenza season<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine Efficacy | Vaccine efficacy will be assessed through documentation of the incidence of laboratory confirmed influenza and other respiratory viruses in the children receiving LAIV compared to unvaccinated sibling controls | During 2015/2016 influenza season - precise dates to be set by Public Health England as this varies annually. Approximate duration of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Response to LAIV | To assess the immune response to vaccine and non-vaccine influenza strains before and after a single dose of LAIV administration, with respect to i. serological measures (haemagglutination inhibition titre to specific influenza strain) ii. change in specific nasal IgA responses | Up to 6 weeks following administration of a single dose of LAIV | 
| Incidence of Adverse Events (AE) and Serious Adverse Events (SAEs) in Those Received LAIV | Incidence of adverse events (AE) and serious adverse events (SAEs) in children receiving LAIV, with the following sub-analyses: AEs occurring up to 72 hours after LAIV in participants with a history of atopy / asthma / recurrent wheezing, compared to non-atopic participants. Wheezing / asthma symptoms in subjects given LAIV who have a past medical history of asthma or recurrent wheeze in the 4 weeks prior to vaccine administration vs the 3-4 week period after LAIV. NB: AE data was NOT collected in household controls, as per protocol NB: AE delay not collected in Controls (as per protocol) | Up to 1 month after LAIV administration |