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    Summary
    EudraCT Number:2016-002352-24
    Sponsor's Protocol Code Number:
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-05-23
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2016-002352-24
    A.3Full title of the trial
    Safety of Nasal Influenza Immunisation in Children with Asthma: The SNIFFLE 4 study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Is a nasal spray 'flu vaccine safe for use in children with severe asthma/wheezing?
    A.3.2Name or abbreviated title of the trial where available
    SNIFFLE-4 Study
    A.4.1Sponsor's protocol code number
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorImperial College Healthcare NHS Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPublic Health England (Department of Health Research and Development Directorate)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationImperial College London
    B.5.2Functional name of contact pointDr Paul Turner
    B.5.3 Address:
    B.5.3.1Street AddressPaediatric Research Unit, 7th Floor QEQM Building, St Mary’s Hospital, Praed Street
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeW2 1NY
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02033127754
    B.5.5Fax number02033127571
    B.5.6E-mailp.turner@imperial.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Fluenz Tetra nasal spray suspension Influenza vaccine
    D.2.1.1.2Name of the Marketing Authorisation holderMedImmune, LLC
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameFluenz Tetra
    D.3.4Pharmaceutical form Nasal spray, suspension
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntranasal use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNReassortant influenza virus (live attenuated)
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration numberas above
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Information not present in EudraCT
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Children aged 2-18 years (inclusive), with asthma / recurrent wheezing.
    E.1.1.1Medical condition in easily understood language
    Children aged 2-18 years (inclusive), with asthma / recurrent wheezing.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10001705
    E.1.2Term Allergic asthma
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Is the intranasal LAIV influenza ('flu) vaccine safe in children with "severe" asthma or recurrent wheezing?
    E.2.2Secondary objectives of the trial
    1) Is the intranasal LAIV influenza ('flu) vaccine effective in children?
    2) Is it possible to predict those children with asthma who may be more likely to experience respiratory symptoms in the weeks following LAIV?
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Aged 2 – 18 years old

    2. Physician diagnosis of asthma or recurrent wheezing (by the hospital specialist)

    3. Written informed consent from parent/guardian (or the patient themselves from age 16 years), with assent from children aged 8 years and above wherever possible.
    E.4Principal exclusion criteria
    1. Admission to PICU for respiratory illness in the preceding 2 years.

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

    a. Hypersensitivity to the active ingredients, gelatin or gentamicin (a possible trace residue)
    b. Previous systemic allergic reaction to LAIV
    c. 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
    d. 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.

    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.

    e. 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.
    f. pregnancy

    3. Contraindication to vaccination on that occasion, e.g. due to child being acutely unwell:

    a. Febrile ≥38.0oC in last 72 hours
    b. Acute wheeze in last 72 hours requiring treatment beyond that normally prescribed for regular use by the child’s treating healthcare professional
    c. Recent admission to hospital in last 2 weeks for acute asthma
    d. Current oral steroid for asthma exacerbation or course completed within last 2 weeks
    e. 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.

    *Items 3b-3d are relative contra-indications: Many children with “difficult-to-control” symptoms may meet fail to meet these criteria on a routine basis. Where these are present, the study centre PIs are able to authorise participation on a case-by-case basis, after assessing the child and their lung function at the time of enrolment.

    Recent antihistamine use is not a contra-indication to LAIV administration, but use of any antihistamine in the 96 hours prior to LAIV will be logged on the CRF.

    Administration of another live vaccine (e.g. MMR) within the previous 4 weeks is no longer a contra-indication to LAIV administration, according to updated DoH guidelines.

    NB: See Summary of Product Characteristics for full details of contra-indications to LAIV.
    E.5 End points
    E.5.1Primary end point(s)
    Change in symptom/disease control assessment through validated questionnaire pre- and 4 weeks after LAIV in children with asthma / recurrent wheezing:
    • In children age 2-4 years inclusive: TRACK score
    • In children age 5+ years: Asthma Control Test
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to the end of the influenza vaccination season (end Feb 2017)
    E.5.2Secondary end point(s)
    1. Incidence of adverse events (AE) and serious adverse events (SAEs) in children receiving LAIV:
    • AEs occurring up to 72 hours after LAIV.
    • SAEs unrelated to asthma symptoms with onset up to 72 hours after LAIV
    • Incidence of a ‘significant exacerbation’ in asthma, defined as:
    i. At least 3 day course of oral steroids following an unscheduled contact with a healthcare professional; OR
    ii. Unscheduled visit to an Emergency department or admission to hospital for treatment of asthma symptoms, requiring systemic corticosteroids

    2. Vaccine efficacy in the 2016/17 influenza season, through documentation of the incidence of laboratory confirmed influenza and other respiratory viruses in children receiving LAIV
    E.5.2.1Timepoint(s) of evaluation of this end point
    Delayed events will be assessed by telephone follow-up within 4-7 days of vaccination.
    Asthma control will be assessed by validated questionnaire pre and 4 weeks post LAIV.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned14
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of surveillance period (approx May 2017)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days20
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days20
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 840
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 560
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 260
    F.1.2Adults (18-64 years) No
    F.1.2.1Number of subjects for this age range: 20
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state840
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 840
    F.4.2.2In the whole clinical trial 840
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    As per expected normal treatment
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-06-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-08-02
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-03-31
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