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    Clinical Trial Results:
    A Randomized, Double-blind, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children

    Summary
    EudraCT number
    2009-013326-17
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    27 Dec 2010

    Results information
    Results version number
    v1(current)
    This version publication date
    31 Jan 2016
    First version publication date
    31 Jan 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MI-CP208
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01091246
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Gaithersburg, United States, MD 20878
    Public contact
    Clinical Trial Enquiries, MedImmune, LLC, clinicaltrialenquiries@medimmune.com
    Scientific contact
    Raburn Mallory, Sr Director Clinical Development, MedImmune, LLC, RaburnM@MedImmune.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001051-PIP01-10
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Dec 2010
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Dec 2010
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to demonstrate the immunologic non-inferiority of quadrivalent live, attenuated influenza vaccine (MEDI3250) (Q/LAIV) to FluMist in children 2 to 17 years of age by comparing the post dose strain specific geometric mean titers (GMT) of serum hemagglutination inhibition (HAI) antibody.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participants signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    29 Mar 2010
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    6 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 2312
    Worldwide total number of subjects
    2312
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    1993
    Adolescents (12-17 years)
    319
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    A total of 2,481 participants provided written informed consent and were screened for the study. Of these, 2,312 participants were randomized into the study between 29Mar2010 to 12May2010 at 97 sites in the USA.

    Pre-assignment
    Screening details
    Eligible participants were randomized in a 3:1:1 ratio to receive Q/LAIV, FluMist/B/Yamagata, or FluMist/B/Victoria. Randomization was stratified by age (2 to 8 years, 9 to 17 years). For subjects 2 to 8 years of age only, randomization was also stratified by previous seasonal influenza vaccination history.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Q/LAIV (MEDI3250)
    Arm description
    Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]).
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI3250
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray, suspension
    Routes of administration
    Nasal use
    Dosage and administration details
    Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]).

    Arm title
    FluMist/B/Yamagata
    Arm description
    FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]).
    Arm type
    Active comparator

    Investigational medicinal product name
    FluMist-Y
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray, suspension
    Routes of administration
    Nasal use
    Dosage and administration details
    FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]).

    Arm title
    FluMist/B/Victoria
    Arm description
    FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]).
    Arm type
    Active comparator

    Investigational medicinal product name
    FluMist-V
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Nasal spray, suspension
    Routes of administration
    Nasal use
    Dosage and administration details
    FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]).

    Number of subjects in period 1
    Q/LAIV (MEDI3250) FluMist/B/Yamagata FluMist/B/Victoria
    Started
    1385
    464
    463
    Completed
    1350
    448
    450
    Not completed
    35
    16
    13
         Subject not dosed
    2
    -
    1
         Adverse event, non-fatal
    1
    -
    1
         Consent withdrawn by subject
    9
    5
    4
         Lost to follow-up
    23
    11
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Q/LAIV (MEDI3250)
    Reporting group description
    Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]).

    Reporting group title
    FluMist/B/Yamagata
    Reporting group description
    FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]).

    Reporting group title
    FluMist/B/Victoria
    Reporting group description
    FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]).

    Reporting group values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata FluMist/B/Victoria Total
    Number of subjects
    1385 464 463
    Age categorical
    Units: Subjects
    Age Continuous |
    Units: years
        arithmetic mean (standard deviation)
    6.7 ± 3.8 6.8 ± 3.8 6.8 ± 3.9 -
    Gender, Male/Female
    Units: participants
        Female
    707 229 240 1176
        Male
    678 235 223 1136

    End points

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    End points reporting groups
    Reporting group title
    Q/LAIV (MEDI3250)
    Reporting group description
    Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]).

    Reporting group title
    FluMist/B/Yamagata
    Reporting group description
    FluMist/B/Yamagata (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza strains (A/H1N1 [South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Yamagata [B/Florida/4/2006]).

    Reporting group title
    FluMist/B/Victoria
    Reporting group description
    FluMist/B/Victoria (trivalent live attenuated influenza vaccine) was supplied in the BD Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 FFU of each of 3 temperature sensitive, cold-adapted, attenuated, 6:2 reassortant influenza stains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], and B/Victoria [B/Malaysia/2506/2004]).

    Subject analysis set title
    All FluMist Group: Immunogenicity Population
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The Immunogenicity Population included all participants who received any investigational product and had post dose HAI antibody measurement and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.

    Subject analysis set title
    All FluMist Group: A/H1N1
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1320; All FM=878).

    Subject analysis set title
    All FluMist Group: A/H3N2
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1320; All FM=879).

    Subject analysis set title
    All FluMist Group: Serosusceptible to A/H1N1
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=569; All FM=392).

    Subject analysis set title
    All FluMist Group: Serosusceptible to A/H3N2
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=435; All FM=298).

    Subject analysis set title
    All FluMist Group: Seronegative to A/H1N1
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=460; All FM=321).

    Subject analysis set title
    All FluMist Group: Seronegative to A/H3N2
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=364; All FM=244).

    Subject analysis set title
    Post Dose 1 solicited symptoms analyses
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. The total number of subjects evaluable for post Dose 1 solicited symptoms analyses (SSA) were reported.

    Subject analysis set title
    Post-dose 1 solicited symptoms analyses: 2-dose group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. The number of subjects evaluable for post Dose 1 solicited symptoms analyses for two-dose group were reported.

    Subject analysis set title
    Post Dose 2 solicited symptoms analyses
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined. The total number of subjects evaluable for post Dose 2 solicited symptoms analyses were reported.

    Subject analysis set title
    All FluMist Group: Safety population
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    The Safety Population included all participants who received any investigational product and had safety data available. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.

    Subject analysis set title
    Safety population: Two-dose group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received a different investigational product at Dose 2 than at Dose 1 were excluded from the Safety Population for Dose 2. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.

    Subject analysis set title
    Evaluable Safety population: Two-dose group
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants who received a different investigational product at Dose 2 than at Dose 1 were excluded from the Safety Population for Dose 2. Evaluable subjects of the two-doe group were reported. All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined.

    Primary: The 4 post-dose strain-specific serum hemagglutination inhibition (HAI) antibody geometric mean titers (GMT) in the Q/LAIV (MEDI3250) arm are noninferior to those in the comparator FluMist group.

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    End point title
    The 4 post-dose strain-specific serum hemagglutination inhibition (HAI) antibody geometric mean titers (GMT) in the Q/LAIV (MEDI3250) arm are noninferior to those in the comparator FluMist group.
    End point description
    Non-inferior immune response was defined as having the upper bound of the 2-sided 95% confidence intervals (CIs) for the HAI antibody GMT ratio (FluMist comparator divided by Q/LAIV) ≤ 1.5 for each of the 4 strains. In the below table, '99999' indicates data was not reported since, the comparators for the GMT ratios for the primary endpoint were participants in the All FluMist group (combined data for both FluMist arms) for A/H1N1 and A/H3N2 strains. '88888' indicates data was not reported since B/Yamagata strain not in the investigational product. '77777' indicates data was not reported since B/Victoria strain not in the investigational product. All participants who received any investigational product (Q=1385; FY=464; FV=463; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; FY=445; FV=437; All FM=883).
    End point type
    Primary
    End point timeframe
    Day 28 post immunogenicity dose
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata FluMist/B/Victoria All FluMist Group: Immunogenicity Population
    Number of subjects analysed
    1327
    445
    437
    883
    Units: Geometric mean titer
    geometric mean (full range (min-max))
        A/H1N1
    16.7 (15.9 to 17.6)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    17.9 (16.8 to 19.1)
        A/H3N2
    27.7 (26.1 to 29.4)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    28.8 (26.7 to 31.1)
        B/Yamagata
    49.6 (46.6 to 52.8)
    59.8 (53.7 to 66.7)
    88888 (88888 to 88888)
    99999 (99999 to 99999)
        B/Victoria
    35.4 (33.3 to 37.7)
    77777 (77777 to 77777)
    37 (33.4 to 41)
    99999 (99999 to 99999)
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    A/H1N1: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Yamagata + FluMist/B/Victoria) / (Q/LAIV) for A/H1N1 strain
    Comparison groups
    Q/LAIV (MEDI3250) v All FluMist Group: Immunogenicity Population
    Number of subjects included in analysis
    2210
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    Method
    Bootstrapping
    Parameter type
    Ratio of geometric mean
    Point estimate
    1.07
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.98
         upper limit
    1.16
    Notes
    [1] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    A/H3N2: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Yamagata + FluMist/B/Victoria) / (Q/LAIV) for A/H3N2 strain
    Comparison groups
    Q/LAIV (MEDI3250) v All FluMist Group: Immunogenicity Population
    Number of subjects included in analysis
    2210
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    Method
    Bootstrapping
    Parameter type
    Ratio of geometric means
    Point estimate
    1.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.94
         upper limit
    1.14
    Notes
    [2] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5. If the upper bounds of 95% CIs were ≤ 1.5 for all 4 strains, the immunologic noninferiority of Q/LAIV compared to FluMist was declared.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    B/Yamagata: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Yamagata) / (Q/LAIV) for B/Yamagata strain
    Comparison groups
    Q/LAIV (MEDI3250) v FluMist/B/Yamagata
    Number of subjects included in analysis
    1772
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    Method
    Parameter type
    Ratio of geometric mean
    Point estimate
    1.21
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.07
         upper limit
    1.37
    Notes
    [3] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5. If the upper bounds of 95% CIs were ≤ 1.5 for all 4 strains, the immunologic noninferiority of Q/LAIV compared to FluMist was declared.
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    B/Victoria: The statistical hypothesis testing for the primary endpoint for Q/LAIV was: H0: Rj > 1.5, for any j HA: Rj ≤ 1.5, for all j Where Rj was any of the 4 strain-specific post immunogenicity dose GMT ratios: (FluMist/B/Victoria) / (Q/LAIV) for B/Victoria strain
    Comparison groups
    Q/LAIV (MEDI3250) v FluMist/B/Victoria
    Number of subjects included in analysis
    1764
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [4]
    Method
    Parameter type
    Ratio of geometric mean
    Point estimate
    1.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.93
         upper limit
    1.18
    Notes
    [4] - The noninferior immune response was assessed by evaluating the upper bound of the two-sided 95% confidence intervals for the strain specific HAI antibody GMT ratios (FluMist divided by Q/LAIV) to the noninferiority margin of 1.5. If the upper bounds of 95% confidence intervals were ≤ 1.5 for all 4 strains, the immunologic noninferiority of Q/LAIV compared to FluMist was declared.

    Secondary: The Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose

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    End point title
    The Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose [5]
    End point description
    Seroresponse was defined as a ≥ 4-fold rise in HAI antibody titer from baseline. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1320; All FM=878).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: A/H1N1
    Number of subjects analysed
    1320
    878
    Units: percent of participants
        number (not applicable)
    6.3
    8.2
    No statistical analyses for this end point

    Secondary: Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose

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    End point title
    Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose [6]
    End point description
    Seroresponse was defined as a ≥ 4-fold rise in HAI antibody titer from baseline. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1321; All FM=879).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: A/H3N2
    Number of subjects analysed
    1321
    879
    Units: Percent of participants
        number (not applicable)
    3.9
    3.6
    No statistical analyses for this end point

    Secondary: Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose

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    End point title
    Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose [7]
    End point description
    Seroresponse was defined as a ≥ 4-fold rise in HAI antibody titer from baseline. All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1321; FY=441).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata
    Number of subjects analysed
    1321
    441
    Units: Percent of participants
        number (not applicable)
    43.4
    44.9
    No statistical analyses for this end point

    Secondary: Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose

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    End point title
    Percent of Participants (Regardless of Serostatus) Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose [8]
    End point description
    Seroresponse was defined as a ≥ 4-fold rise from baseline. All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1321; FV=437).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Victoria
    Number of subjects analysed
    1321
    437
    Units: Percent of participants
        number (not applicable)
    39.1
    38.4
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose [9]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=569; All FM=392).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Serosusceptible to A/H1N1
    Number of subjects analysed
    569
    392
    Units: Percent of participants
        number (not applicable)
    12.7
    17.6
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose [10]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=435; All FM=298).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Serosusceptible to A/H3N2
    Number of subjects analysed
    435
    298
    Units: Percent of participants
        number (not applicable)
    9.9
    9.4
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose [11]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=588; FY=192).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata
    Number of subjects analysed
    588
    192
    Units: Percent of participants
        number (not applicable)
    79.1
    81.3
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Victoria Strain Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Within Each Treatment Arm Who Experience Seroresponse to the B/Victoria Strain Post Immunogenicity Dose [12]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=620; FV=191).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Victoria
    Number of subjects analysed
    620
    191
    Units: Percent of participants
        number (not applicable)
    66.1
    69.6
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H1N1 Strain Post Immunogenicity Dose [13]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=460; All FM=321).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Seronegative to A/H1N1
    Number of subjects analysed
    460
    321
    Units: Percent of participants
        number (not applicable)
    14.6
    19.6
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the A/H3N2 Strain Post Immunogenicity Dose [14]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response and were seronegative to the strain (Q=364; All FM=244).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Seronegative to A/H3N2
    Number of subjects analysed
    364
    244
    Units: Percent of participants
        number (not applicable)
    9.9
    11.1
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Yamagata Strain Post Immunogenicity Dose [15]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=483; FY=165).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata
    Number of subjects analysed
    483
    165
    Units: Percent of participants
        number (not applicable)
    83
    84.8
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Within Each Treatment Arm Who Experienced a Seroresponse to the B/Victoria Strain Post Immunogenicity Dose [16]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. Seroresponse was defined as a ≥ 4-fold rise in HAI titer from baseline. All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=487; FV=159).
    End point type
    Secondary
    End point timeframe
    Day 0 and Day 28 post immunogenicity dose
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Victoria
    Number of subjects analysed
    487
    159
    Units: Percent of participants
        number (not applicable)
    68.8
    73.6
    No statistical analyses for this end point

    Secondary: Percent of Participants (Regardless of Serostatus) Who Achieved an A/H1N1 or A/H3N2 Strain-specific HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Participants (Regardless of Serostatus) Who Achieved an A/H1N1 or A/H3N2 Strain-specific HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [17]
    End point description
    All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; All FM=883).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Immunogenicity Population
    Number of subjects analysed
    1327
    883
    Units: Percent of participants
    number (not applicable)
        A/H1N1
    43.1
    43.8
        A/H3N2
    55.7
    55.4
    No statistical analyses for this end point

    Secondary: Percent of Participants (Regardless of Serostatus) Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Participants (Regardless of Serostatus) Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [18]
    End point description
    All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; FY=445).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata
    Number of subjects analysed
    1327
    445
    Units: Percent of participants
        number (not applicable)
    76.5
    81.6
    No statistical analyses for this end point

    Secondary: Percent of Participants (Regardless of Serostatus) Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Participants (Regardless of Serostatus) Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [19]
    End point description
    All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, and had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response (Q=1327; FV=437).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Victoria
    Number of subjects analysed
    1327
    437
    Units: Percent of participants
        number (not applicable)
    65.6
    66.6
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Who Achieved an A/H1N1 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Who Achieved an A/H1N1 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [20]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8.
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Serosusceptible to A/H1N1
    Number of subjects analysed
    569
    392
    Units: Percent of participants
        number (not applicable)
    5.1
    6.1
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Who Achieved an A/H3N2 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Who Achieved an A/H3N2 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [21]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=569; All FM=392).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Serosusceptible to A/H3N2
    Number of subjects analysed
    435
    298
    Units: Percent of participants
        number (not applicable)
    4.8
    4.4
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [22]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=435; All FM=298).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata
    Number of subjects analysed
    588
    192
    Units: Percent of participants
        number (not applicable)
    60.9
    69.3
    No statistical analyses for this end point

    Secondary: Percent of Serosusceptible Participants Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Serosusceptible Participants Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [23]
    End point description
    Serosusceptible was defined as a baseline HAI titer ≤ 8. All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=588; FY=192).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Victoria
    Number of subjects analysed
    620
    191
    Units: Percent of participants
        number (not applicable)
    41.1
    44
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Who Achieved an A/H1N1 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Who Achieved an A/H1N1 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [24]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. All participants who received any investigational product (Q=1385; FV=463), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were serosusceptible to the strain (Q=620; FV=191).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Seronegative to A/H1N1
    Number of subjects analysed
    460
    321
    Units: Percent of participants
        number (not applicable)
    5.2
    5.6
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Who Achieved an A/H3N2 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Who Achieved an A/H3N2 HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [25]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=460; All FM=321).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Seronegative to A/H3N2
    Number of subjects analysed
    364
    244
    Units: Percent of participants
        number (not applicable)
    3.8
    4.9
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Who Achieved a B/Yamagata HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [26]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. All participants who received any investigational product (Q=1385; All FM=927), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=364; All FM=244).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Yamagata
    Number of subjects analysed
    483
    165
    Units: Percent of participants
        number (not applicable)
    60.9
    70.9
    No statistical analyses for this end point

    Secondary: Percent of Seronegative Participants Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose

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    End point title
    Percent of Seronegative Participants Who Achieved a B/Victoria HAI Antibody Titer ≥ 32 Post Immunogenicity Dose [27]
    End point description
    Seronegative was defined as a baseline HAI titer ≤ 4. All participants who received any investigational product (Q=1385; FY=464), had post dose HAI antibody measurement at the appropriate time, had no protocol deviation judged to have the potential to interfere with the generation or interpretation of an immune response, and were seronegative to the strain (Q=487; FV=159).
    End point type
    Secondary
    End point timeframe
    Day 28 post immunogenicity dose
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) FluMist/B/Victoria
    Number of subjects analysed
    487
    159
    Units: Percent of Participants
        number (not applicable)
    37
    42.8
    No statistical analyses for this end point

    Secondary: Percent of All Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1

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    End point title
    Percent of All Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1 [28]
    End point description
    Solicited symptoms were fever ≥ 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom. All participants who received any investigational product (Q=1385; All FM=927) and for whom any follow-up solicited symptom safety data were recorded during the summarized period (Q=1377; All FM=920).
    End point type
    Secondary
    End point timeframe
    Days 0-14 Post Dose 1
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) Post Dose 1 solicited symptoms analyses
    Number of subjects analysed
    1377
    920
    Units: Percent of Participants
    number (not applicable)
        Any solicited symptom
    47.9
    47.4
        Fever ≥ 100.4°F (38.0°C)
    5.7
    3.9
        Fever ≥ 101.3°F (38.5°C)
    3.3
    2.3
        Fever ≥ 102.2°F (39.0°C)
    1.4
    0.8
        Fever ≥ 103.1°F (39.5°C)
    0.3
    0.2
        Fever ≥ 104.0°F (40.0°C)
    0.1
    0
        Fever ≥ 104.9°F (40.5°C)
    0
    0
        Runny/stuffy nose
    32.3
    32
        Sore throat
    9.2
    10.3
        Cough
    15.8
    16.8
        Headache
    12.5
    12.2
        Generalized muscle aches
    4.4
    4.6
        Decreased activity level or tiredness/weakness
    9.8
    9.9
        Decreased appetite
    5.5
    6.6
    No statistical analyses for this end point

    Secondary: Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1

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    End point title
    Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Investigational Product Through 14 Days Post Dose 1 [29]
    End point description
    Solicited symptoms were fever ≥ 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom. All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any follow-up solicited symptom safety data were recorded during the summarized period (Q=1078; All FM=716).
    End point type
    Secondary
    End point timeframe
    Days 0-14 Post Dose 1
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) Post-dose 1 solicited symptoms analyses: 2-dose group
    Number of subjects analysed
    1078
    716
    Units: Percent of Participants
    number (not applicable)
        Any solicited symptom
    48.1
    47.5
        Fever ≥ 100.4°F (38.0°C)
    6.6
    4.2
        Fever ≥ 101.3°F (38.5°C)
    4
    2.2
        Fever ≥ 102.2°F (39.0°C)
    1.7
    0.8
        Fever ≥ 103.1°F (39.5°C)
    0.4
    0.3
        Fever ≥ 104.0°F (40.0°C)
    0.1
    0
        Fever ≥ 104.9°F (40.5°C)
    0
    0
        Runny/stuffy nose
    33.8
    31.7
        Sore throat
    8.2
    8.9
        Cough
    17.2
    18
        Headache
    9.7
    10.1
        Generalized muscle aches
    4.5
    4.3
        Decreased activity level or tiredness/weakness
    9.3
    8.2
        Decreased appetite
    5.6
    6.7
    No statistical analyses for this end point

    Secondary: Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Dose 2 During Days 0-14 Post Dose 2

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    End point title
    Percent of Two-dose Participants Experiencing Each Solicited Symptom From Administration of Dose 2 During Days 0-14 Post Dose 2 [30]
    End point description
    Solicited symptoms were fever ≥ 100.4°F (38.0°C), runny/stuffy nose, sore throat, cough, headache, generalized muscle aches, decreased activity level (lethargy) OR tiredness/weakness, decreased appetite. Collection of specific solicited symptoms (sore throat, headache, generalized muscle aches) was omitted when, according to the judgment of the investigator, the subject was too young to reliably report a particular symptom. All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any follow-up solicited symptom safety data were recorded during the summarized period (Q=1039; All FM=692).
    End point type
    Secondary
    End point timeframe
    Days 0-14 Post Dose 2
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) Post Dose 2 solicited symptoms analyses
    Number of subjects analysed
    1039
    692
    Units: Percent of Participants
    number (not applicable)
        Any solicited symptom
    31.4
    30.6
        Fever ≥ 100.4°F (38.0°C)
    2.7
    4.2
        Fever ≥ 101.3°F (38.5°C)
    1.5
    2.3
        Fever ≥ 102.2°F (39.0°C)
    0.8
    1
        Fever ≥ 103.1°F (39.5°C)
    0.3
    0.3
        Fever ≥ 104.0°F (40.0°C)
    0
    0.1
        Fever ≥ 104.9°F (40.5°C)
    0
    0
        Runny/stuffy nose
    20.9
    19.5
        Sore throat
    4.1
    4.6
        Cough
    12.7
    11.7
        Headache
    5.4
    5.5
        Generalized muscle aches
    1.2
    0.9
        Decreased activity level or tiredness/weakness
    5.9
    5.3
        Decreased appetite
    3.7
    3.3
    No statistical analyses for this end point

    Secondary: Percent of All Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1

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    End point title
    Percent of All Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1 [31]
    End point description
    Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
    End point type
    Secondary
    End point timeframe
    Days 0-28 Post Dose 1
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Safety population
    Number of subjects analysed
    1382
    923
    Units: Percent of Participants
        number (not applicable)
    21
    20.7
    No statistical analyses for this end point

    Secondary: Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1

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    End point title
    Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Investigational Product Through Day 28 Post Dose 1 [32]
    End point description
    Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any safety data were recorded during the summarized period (Q=1083; All FM=719).
    End point type
    Secondary
    End point timeframe
    Days 0-28 Post Dose 1
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) Safety population: Two-dose group
    Number of subjects analysed
    1083
    719
    Units: Percent of Participants
        number (not applicable)
    20.3
    22.9
    No statistical analyses for this end point

    Secondary: Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Dose 2 Through 28 Days Post Dose 2

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    End point title
    Percent of Two-dose Participants Experiencing Any Adverse Event From Administration of Dose 2 Through 28 Days Post Dose 2 [33]
    End point description
    Any untoward medical occurrence in a patient or clinical investigation in a subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any post Dose 2 safety data were recorded during the summariezed period (Q=1041; All FM=693).
    End point type
    Secondary
    End point timeframe
    Days 0-28 Post Dose 2
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) Evaluable Safety population: Two-dose group
    Number of subjects analysed
    1041
    693
    Units: Percent of participants
        number (not applicable)
    13.4
    16.7
    No statistical analyses for this end point

    Secondary: Percent of All Participants Reporting Any Serious Adverse Event (SAE) From Administration of Investigational Product Through Day 28 Post Dose 1

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    End point title
    Percent of All Participants Reporting Any Serious Adverse Event (SAE) From Administration of Investigational Product Through Day 28 Post Dose 1 [34]
    End point description
    SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above. All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
    End point type
    Secondary
    End point timeframe
    Days 0-28 Post Dose 1
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Safety population
    Number of subjects analysed
    1382
    923
    Units: Percent of participants
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Percent of Two-dose Participants Reporting Any SAE From Administration of Dose 2 During Days 0-28 Post Dose 2

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    End point title
    Percent of Two-dose Participants Reporting Any SAE From Administration of Dose 2 During Days 0-28 Post Dose 2 [35]
    End point description
    SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above. All two-dose participants who received any investigational product (Q=1083; All FM=719) and for whom any post Dose 2 safety data were recorded during the summarized period (Q=1041; All FM=693).
    End point type
    Secondary
    End point timeframe
    Days 0-28 Post Dose 2
    Notes
    [35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) Evaluable Safety population: Two-dose group
    Number of subjects analysed
    1041
    693
    Units: Percent of participants
        number (not applicable)
    0.2
    0.1
    No statistical analyses for this end point

    Secondary: Percent of All Participants Reporting Any SAE From Administration of Investigational Product Through 180 Days Post Last Dose

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    End point title
    Percent of All Participants Reporting Any SAE From Administration of Investigational Product Through 180 Days Post Last Dose [36]
    End point description
    SAEs were those AEs that resulted in death; were immediately life threatening; resulted in inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; were a congenital anomaly in the offspring of a participant; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgement, may have jeopardized the participant and may have required medical or surgical intervention to prevent on the outcomes listed above. All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
    End point type
    Secondary
    End point timeframe
    Days 0-180 Post Last Dose
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Safety population
    Number of subjects analysed
    1382
    923
    Units: Percent of participants
        number (not applicable)
    0.4
    0.5
    No statistical analyses for this end point

    Secondary: Percent of All Participants Reporting Any New Onset Chronic Disease (NOCD) From Administration of Investigational Product Through 180 Days Post Last Dose

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    End point title
    Percent of All Participants Reporting Any New Onset Chronic Disease (NOCD) From Administration of Investigational Product Through 180 Days Post Last Dose [37]
    End point description
    An NOCD was a newly diagnosed medical condition that was of a chronic, ongoing nature and was assessed by the investigator as medically significant. All participants who received any investigational product (Q=1385; All FM=927) and for whom any safety data were recorded during the summarized period (Q=1382; All FM=923).
    End point type
    Secondary
    End point timeframe
    Days 0-180 Post Last Dose
    Notes
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint was related to these respective arms only, hence not reporting statistics for all the arms in the baseline period.
    End point values
    Q/LAIV (MEDI3250) All FluMist Group: Safety population
    Number of subjects analysed
    1382
    923
    Units: Percent of participants
        number (not applicable)
    1.4
    0.8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from Day 0 through 28 after Doses 1 and 2. Serious adverse events were collected between Days 0-180 after the last dose administered.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    12.0
    Reporting groups
    Reporting group title
    All FluMist Group
    Reporting group description
    All FluMist group for A/H1N1 and A/H3N2 strains, where data from both the FluMist/B/Yamagata arm and the FluMist/B/Victoria arm were combined

    Reporting group title
    Q/LAIV (MEDI3250)
    Reporting group description
    Q/LAIV (quadrivalent live attenuated influenza vaccine) (MEDI3250) was supplied in the Becton Dickinson (BD) Accuspray device that delivers a 0.2 mL total volume intranasal dose divided into each nostril (ie, administered as 0.1 mL per nostril). Each 0.2 mL dose contained 10^7.0 ± 0.5 fluorescent focus units (FFU) of each of 4 temperature sensitive, cold-adapted, attenuated, 6:2 resassortant influenza strains (A/H1N1 [A/South Dakota/6/2007], A/H3N2 [A/Uruguay/716/2007], B/Victoria [B/Malaysia/2506/2004], and B/Yamagata [B/Florida/4/2006]).

    Serious adverse events
    All FluMist Group Q/LAIV (MEDI3250)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 923 (0.54%)
    6 / 1382 (0.43%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    1 / 923 (0.11%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 923 (0.00%)
    1 / 1382 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung injury
         subjects affected / exposed
    1 / 923 (0.11%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pneumothorax
         subjects affected / exposed
    1 / 923 (0.11%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 923 (0.11%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Major depression
         subjects affected / exposed
    1 / 923 (0.11%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Pelvi-ureteric obstruction
         subjects affected / exposed
    1 / 923 (0.11%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 923 (0.00%)
    1 / 1382 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 923 (0.00%)
    1 / 1382 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 923 (0.00%)
    1 / 1382 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 923 (0.00%)
    1 / 1382 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 923 (0.00%)
    1 / 1382 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 923 (0.00%)
    1 / 1382 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 923 (0.11%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 923 (0.22%)
    0 / 1382 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    All FluMist Group Q/LAIV (MEDI3250)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    105 / 923 (11.38%)
    176 / 1382 (12.74%)
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    16 / 923 (1.73%)
    27 / 1382 (1.95%)
         occurrences all number
    17
    27
    RHINORRHOEA
         subjects affected / exposed
    17 / 923 (1.84%)
    22 / 1382 (1.59%)
         occurrences all number
    17
    23
    SNEEZING
         subjects affected / exposed
    8 / 923 (0.87%)
    16 / 1382 (1.16%)
         occurrences all number
    10
    17
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    6 / 923 (0.65%)
    23 / 1382 (1.66%)
         occurrences all number
    8
    23
    Gastrointestinal disorders
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    12 / 923 (1.30%)
    10 / 1382 (0.72%)
         occurrences all number
    14
    12
    DIARRHOEA
         subjects affected / exposed
    19 / 923 (2.06%)
    22 / 1382 (1.59%)
         occurrences all number
    19
    22
    VOMITING
         subjects affected / exposed
    20 / 923 (2.17%)
    36 / 1382 (2.60%)
         occurrences all number
    21
    37
    Infections and infestations
    OTITIS MEDIA
         subjects affected / exposed
    12 / 923 (1.30%)
    12 / 1382 (0.87%)
         occurrences all number
    12
    12
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    11 / 923 (1.19%)
    8 / 1382 (0.58%)
         occurrences all number
    11
    8

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Sep 2009
    Major changes to the study design incorporated in Amendment 1 were: 1) Entire protocol: Remove the blow-fill-seal (BFS) arm; QLAIV was only provided in the BD Accuspray device. This resulted in a change in number of subjects enrolled. The inclusion of the BFS arm did not permit complete blinding of the investigational product due to the differences between the Accuspray and BFS devices. Because the BFS arm was removed, the study was now completely blinded. The protocol title was therefore changed from “A Randomized, Partially Blinded, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children” to its current title of “A Randomized, Double-Blind, Active Controlled Study to Evaluate the Immunogenicity of Quadrivalent LAIV in Children” 2) Section 7.3.1 (Primary Endpoint): Amended the statistical analysis section so that the primary endpoint was met if the upper bound of the two-sided 95% CIs for the strainspecific HAI antibody GMT ratios (FluMist divided by Q/LAIV) was ≤ 2 for all 4 strains. 3) Section 7.3.2 (Secondary Endpoints): Amended the definition of seronegative and serosusceptible to include HAI antibody values that were not whole numbers, because each time point was assayed in duplicate, and if the results were within one dilution, the GMT was calculated and used for analysis. Values that differed by more than one dilution for a single specimen were repeated. 4) Section 5.2 (Schedule of Study Procedures): Added a temperature log, which was to be collected. Clarified that a memory aid was supplied to subjects, but it was not considered to be source data and was not collected. 5) Section 1.4.1 (Safety of Q/LAIV in Study MI-CP185): Provided data from on-going Study MI-CP185, a study of Q/LAIV in adults.
    09 Mar 2010
    Major changes to the study incorporated in Amendment 2 were: 1) Added unblinded MI-CP185 safety and immunogenicity data. 2) Entire protocol: Clarified that the subject history of prior influenza vaccination that was used to stratify enrollment and to assign the timing of the immunogenicity blood sample was a history of prior seasonal influenza vaccination, because of the possibility that children might have received a prior influenza vaccine that consisted only of monovalent pandemic H1N1. 3) Entire protocol: Amended the noninferiority margin from 2.0 to 1.5 in accordance with guidance from the US FDA. 4) Abstract, Overview of Study Design and Treatment Assignment: Removed site as a stratification factor for randomization, 5) Exclusion Criteria: Modified the concomitant medications window around exclusion criteria numbers 4, 5, 7, 8, 12, 14 from 30 days to 28 days to be consistent with the concomitant medication reporting period and clarified that salicylate-containing medications were prohibited. 6) Exclusion Criteria: Added, “A history of epilepsy, seizure, or an evolving neurological condition except that a single febrile seizure that occurred 3 or more years prior to enrollment would not disqualify a subject” in accordance with guidance from the Canadian IRB. 7) Blinding: Clarified that all MedImmune staff were unblinded for the Day 28 safety and immunogenicity analyses, but site staff, CRO staff, and subjects were to remain blinded until the Day 180 final database lock 8) Concomitant Medications: Modified concomitant medications windows to be consistent with the concomitant medication reporting period and clarified that salicylate-containing medications were prohibited. 9) Clarified the relationship between severity Grading 1-5 and the wording mild, moderate, severe, life-threatening and fatal, because the EDC system contained these words.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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