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    Clinical Trial Results:
    A Phase IIA, open-label study to evaluate the immunogenicity and safety of sequential use of GSK’s investigational vaccine GSK3277511A when administered to healthy smokers and ex-smokers aged 50 to 80 years following receipt of Shingrix vaccine

    Summary
    EudraCT number
    		 2018-002977-24
    Trial protocol
    		 ES   FI   FR   IT  
    Global end of trial date
    13 Aug 2021

    Results information
    Results version number
    		 v2(current)
    This version publication date
    11 Jun 2022
    First version publication date
    22 Sep 2021
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    209538
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03894969
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    GSK Response Center, GSKClinicalSupportHD@gsk.com, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 044 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    03 Nov 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Aug 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the non-inferiority (NI) of the humoral immune response 1 month after Dose 2 of GSK’s Non-Typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) vaccine adjuvanted with AS01E, when administered after vaccination with the AS01B-adjuvanted Shingrix vaccine.
    Protection of trial subjects
    The subjects were observed closely for at least 30 minutes following the administration of the vaccines, with appropriate medical treatment readily available in case of anaphylaxis.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Apr 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Estonia: 193
    Country: Number of subjects enrolled
    Finland: 156
    Country: Number of subjects enrolled
    France: 60
    Country: Number of subjects enrolled
    Italy: 66
    Country: Number of subjects enrolled
    Spain: 66
    Worldwide total number of subjects
    541
    EEA total number of subjects
    541
    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)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    396
    From 65 to 84 years
    145
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 542 participants were enrolled in the study, but only 541 received at least 1 dose of study treatment (i.e. Shingrix and/or NTHi Mcat vaccine).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Sh_NTHi-Mcat_1 Group
    Arm description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, and following a 1-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 91, and Day 151.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Shingrix, NTHi-Mcat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 2 doses of GSK’s Shingrix vaccine at Day 1, Day 61 and, following a 1-month gap, 2 doses of GSK Biological’s NTHi-Mcat investigational vaccine at Day 91, and Day 151.

    Arm title
    		 Sh_NTHi-Mcat_3 Group
    Arm description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 3-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 151 and Day 211.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Shingrix, NTHi-Mcat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 2 doses of GSK’s Shingrix vaccine at Day 1, Day 61 and, following a 3-month gap, 2 doses of GSK Biological’s NTHi-Mcat investigational vaccine at Day 151 and Day 211.

    Arm title
    		 Sh_NTHi-Mcat_6 Group
    Arm description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 6-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart at Day 241 and Day 301.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Shingrix, NTHi-Mcat
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 2 doses of GSK’s Shingrix vaccine at Day 1, Day 61 and, following a 6-month gap, 2 doses of GSK Biological’s NTHi-Mcat investigational vaccine at Day 241 and Day 301.

    Arm title
    		 NTHi-Mcat Group
    Arm description
    		 Subjects enrolled in this group received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 1 and Day 61.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    NTHi-Mcat investigational vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 2 doses of GSK’s NTHi-Mcat investigational vaccine at Day 1 and Day 61.

    Arm title
    		 Shingrix-Only Group
    Arm description
    		 Subjects belonging to this group were originally randomized to either Sh_NTHi-Mcat_1 Group, Sh_NTHi-Mcat_3 Group or Sh_NTHi-Mcat_6 Group, they received at least 1, maximum 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, but didn't receive any dose of NTHI Mcat investigational vaccine. Only safety data were collected for these subjects.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Shingrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received at least 1, maximum 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61.

    Number of subjects in period 1
    		Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group Shingrix-Only Group
    Started
    134
    134
    122
    135
    16
    Completed
    129
    129
    118
    128
    2
    Not completed
    5
    5
    4
    7
    14
         Consent withdrawn by subject
    2
    1
    3
    4
    8
         Adverse event, non-fatal
    -
    2
    -
    1
    2
         Solicited Adverse Event
    -
    1
    -
    -
    -
         Not specified
    -
    -
    -
    -
    3
         Lost to follow-up
    3
    1
    1
    -
    -
         Unsolicited Non-Serious Adverse Event
    -
    -
    -
    2
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Sh_NTHi-Mcat_1 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, and following a 1-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 91, and Day 151.

    Reporting group title
    Sh_NTHi-Mcat_3 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 3-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 151 and Day 211.

    Reporting group title
    Sh_NTHi-Mcat_6 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 6-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart at Day 241 and Day 301.

    Reporting group title
    NTHi-Mcat Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 1 and Day 61.

    Reporting group title
    Shingrix-Only Group
    Reporting group description
    		 Subjects belonging to this group were originally randomized to either Sh_NTHi-Mcat_1 Group, Sh_NTHi-Mcat_3 Group or Sh_NTHi-Mcat_6 Group, they received at least 1, maximum 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, but didn't receive any dose of NTHI Mcat investigational vaccine. Only safety data were collected for these subjects.

    Reporting group values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group Shingrix-Only Group Total
    Number of subjects
    		 134 134 122 135 16 541
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 95 103 82 104 12 396
        From 65-84 years
    		 39 31 40 31 4 145
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 60.7 ( 7.0 ) 60.9 ( 6.7 ) 60.5 ( 7.1 ) 60.0 ( 7.1 ) 62.4 ( 5.5 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 63 66 58 65 7 259
        Male
    		 71 68 64 70 9 282
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian Or Alaska Native
    		 1 0 0 1 0 2
        Black Or African American
    		 0 1 0 1 0 2
        Not Reported
    		 0 0 0 0 1 1
        Other
    		 4 3 2 4 4 17
        White
    		 129 130 120 129 11 519

    End points

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    End points reporting groups
    Reporting group title
    Sh_NTHi-Mcat_1 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, and following a 1-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 91, and Day 151.

    Reporting group title
    Sh_NTHi-Mcat_3 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 3-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 151 and Day 211.

    Reporting group title
    Sh_NTHi-Mcat_6 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 6-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart at Day 241 and Day 301.

    Reporting group title
    NTHi-Mcat Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 1 and Day 61.

    Reporting group title
    Shingrix-Only Group
    Reporting group description
    		 Subjects belonging to this group were originally randomized to either Sh_NTHi-Mcat_1 Group, Sh_NTHi-Mcat_3 Group or Sh_NTHi-Mcat_6 Group, they received at least 1, maximum 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, but didn't receive any dose of NTHI Mcat investigational vaccine. Only safety data were collected for these subjects.

    Primary: Anti-Protein D (PD), Anti-Protein E (PE), Anti-type IV pili subunit (PilA) and Anti-ubiquitous surface protein A2 of Moraxella catarrhalis (UspA2) Adjusted Geometric Mean Concentrations (GMCs), one-month post Dose-2 of NTHi-Mcat vaccine

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    End point title
    		 Anti-Protein D (PD), Anti-Protein E (PE), Anti-type IV pili subunit (PilA) and Anti-ubiquitous surface protein A2 of Moraxella catarrhalis (UspA2) Adjusted Geometric Mean Concentrations (GMCs), one-month post Dose-2 of NTHi-Mcat vaccine [1]
    End point description
    Antibody concentrations as measured by ELISA (Enzyme-linked immunosorbent assay) and expressed as adjusted (ANCOVA model) GMCs in ELISA units per milliliter (EU/mL). Cut-off value for the assay is 153,16,8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively. The ANCOVA model includes study group, smoking status (current or former), age category (50-59, 60-69, 70-80 years of age) and center as factors and the antibody concentration before Dose 1 as covariate. Analysis was performed on the per protocol set (PPS) which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. As PPS sample size was not met in Sh_NTHi_Mcat_3 and Sh_NTHi-Mcat_6 groups,those were not part of the analysis and timeframe was adapted. Shingrix-Only Group was not included in this analysis,as subjects didn't receive the NTHi MCAT vaccine.
    End point type
    Primary
    End point timeframe
    At 1 month after dose 2 of NTHi-Mcat vaccine (Day 181, in Sh_NTHi-Mcat_1 group and Day 91 in NTHi-Mcat group)
    Notes
    [1] - 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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group NTHi-Mcat Group
    Number of subjects analysed
    118
    124
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-PD (N=118;123)
    1402.804 (1139.194 to 1727.414)
    1489.531 (1203.846 to 1843.014)
        Anti-PE (N=118;124)
    6234.827 (5053.049 to 7692.992)
    7032.52 (5666.105 to 8728.452)
        Anti-PilA (N=117;124)
    1244.373 (963.063 to 1607.854)
    1089.799 (840.246 to 1413.47)
        Anti-UspA2 (N=118;124)
    1022.961 (894.403 to 1169.998)
    941.45 (820.993 to 1079.58)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    To demonstrate the non-inferiority (NI) of the humoral immune response 1 month after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine when administered 1 after Shingrix vaccine versus the humoral immune response 1 month after Dose 2 of GSKBiologicals' NTHi-Mcat investigational vaccine alone.
    Comparison groups
    Sh_NTHi-Mcat_1 Group v NTHi-Mcat Group
    Number of subjects included in analysis
    242
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    Method
    		 ANCOVA
    Parameter type
    		 GMC ratio
    Point estimate
    0.942
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.765
         upper limit
    		 1.159
    Notes
    [2] - Non-inferiority is concluded if the lower limit of the two sided 95% CI for the GMC ratio for anti-PD is > 0.667. The anti-PD GMC ratio is presented in this test with its 95% CI.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    To demonstrate the non-inferiority (NI) of the humoral immune response 1 month after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine when administered 1 after Shingrix vaccine versus the humoral immune response 1 month after Dose 2 of GSKBiologicals' NTHi-Mcat investigational vaccine alone.
    Comparison groups
    Sh_NTHi-Mcat_1 Group v NTHi-Mcat Group
    Number of subjects included in analysis
    242
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    Method
    		 ANCOVA
    Parameter type
    		 GMC ratio
    Point estimate
    0.887
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.719
         upper limit
    		 1.093
    Notes
    [3] - Non-inferiority is concluded if the lower limit of the two sided 95% CI for the GMC ratio for anti-PE is > 0.667. The anti-PE GMC ratio is presented in this test with its 95% CI.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    To demonstrate the non-inferiority (NI) of the humoral immune response 1 month after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine when administered 1 after Shingrix vaccine versus the humoral immune response 1 month after Dose 2 of GSKBiologicals' NTHi-Mcat investigational vaccine alone.
    Comparison groups
    Sh_NTHi-Mcat_1 Group v NTHi-Mcat Group
    Number of subjects included in analysis
    242
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    Method
    		 ANCOVA
    Parameter type
    		 GMC ratio
    Point estimate
    1.142
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.884
         upper limit
    		 1.474
    Notes
    [4] - Non-inferiority is concluded if the lower limit of the two sided 95% CI for the GMC ratio for anti-PilA is > 0.667. The anti-PilA GMC ratio is presented in this test with its 95% CI.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    To demonstrate the non-inferiority (NI) of the humoral immune response 1 month after Dose 2 of GSK Biologicals' NTHi-Mcat investigational vaccine when administered 1 after Shingrix vaccine versus the humoral immune response 1 month after Dose 2 of GSKBiologicals' NTHi-Mcat investigational vaccine alone.
    Comparison groups
    Sh_NTHi-Mcat_1 Group v NTHi-Mcat Group
    Number of subjects included in analysis
    242
    Analysis specification
    Pre-specified
    Analysis type
    		 [5]
    Method
    		 ANCOVA
    Parameter type
    		 GMC ratio
    Point estimate
    1.087
    Confidence interval
         level
    		 0.95%
         sides
    2-sided
         lower limit
    		 0.948
         upper limit
    		 1.245
    Notes
    [5] - Non-inferiority is concluded if the lower limit of the two sided 95% CI for the GMC ratio for anti-UspA2 is > 0.667. The anti-UspA2 GMC ratio is presented in this test with its 95% CI.

    Secondary: Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibody concentrations in terms of GMCs, before first NTHi-Mcat vaccine

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    End point title
    		 Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibody concentrations in terms of GMCs, before first NTHi-Mcat vaccine [6]
    End point description
    GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations). Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.
    End point type
    Secondary
    End point timeframe
    Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 for Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 for NTHi-Mcat group)
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    118
    96
    73
    124
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-PD (N=118;95;73;124)
    94.7 (86.2 to 104.1)
    105.1 (89.8 to 123)
    95.6 (84.5 to 108.3)
    105.3 (93.4 to 118.6)
        Anti-PE (N=118;96;73;123)
    22 (18 to 26.9)
    21.2 (17.6 to 25.4)
    18.6 (14.3 to 24.2)
    23.9 (19.8 to 28.9)
        Anti-PilA (N=118;96;73;124)
    7.8 (6.6 to 9.3)
    10.5 (8.2 to 13.5)
    9.7 (7.5 to 12.6)
    9.1 (7.5 to 11)
        Anti-UspA2 (N=118;96;73;124)
    352.4 (292.5 to 424.7)
    343 (286.3 to 411)
    440.3 (343.5 to 564.5)
    521.4 (441 to 616.3)
    No statistical analyses for this end point

    Secondary: Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibody concentrations in terms of GMCs, one-month post Dose-2 of NTHi-Mcat vaccine

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    End point title
    		 Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibody concentrations in terms of GMCs, one-month post Dose-2 of NTHi-Mcat vaccine [7]
    End point description
    GMCs and their 95% CI for each of the antibodies, as measured by ELISA, were calculated (the GMCs were computed by taking the Anti-log of the mean of the log concentration transformations) before the first dose of NTHi-Mcat vaccine. Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.
    End point type
    Secondary
    End point timeframe
    At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    118
    96
    73
    124
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-PD (N=118;96;73;123)
    1496.7 (1272.7 to 1760.1)
    1504 (1209.9 to 1869.6)
    1539 (1277.3 to 1854.2)
    1683.5 (1434.5 to 1975.5)
        Anti-PE (N=118;96;73;124)
    5911.8 (5121.3 to 6824.3)
    5920.8 (4868.4 to 7200.8)
    6048.5 (4943.3 to 7400.8)
    6562.4 (5660.9 to 7607.5)
        Anti-PilA (N=117;96;73;124)
    1089.3 (910.3 to 1303.4)
    1030.6 (839.4 to 1265.3)
    1114.7 (864.9 to 1436.6)
    999.3 (830.3 to 1202.7)
        Anti-UspA2 (N=118;96;73;124)
    926.8 (796.6 to 1078.4)
    942.2 (819.6 to 1083.2)
    1289.2 (1062.5 to 1564.5)
    1066.4 (946.6 to 1201.4)
    No statistical analyses for this end point

    Secondary: Percentage of seropositive subjects for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibodies before first NTHi-Mcat vaccine

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    End point title
    		 Percentage of seropositive subjects for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibodies before first NTHi-Mcat vaccine [8]
    End point description
    A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI is defined using the assay lower limit of quantification (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively. Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.
    End point type
    Secondary
    End point timeframe
    Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    118
    96
    73
    124
    Units: Percentage of subjects
    number (confidence interval 95%)
        Anti-PD (N=118;95;73;124)
    16.9 (10.7 to 25)
    20 (12.5 to 29.5)
    19.2 (10.9 to 30.1)
    21.8 (14.9 to 30.1)
        Anti-PE (N=118;96;73;123)
    57.6 (48.2 to 66.7)
    63.5 (53.1 to 73.1)
    50.7 (38.7 to 62.6)
    61.8 (52.6 to 70.4)
        Anti-PilA (N=118;96;73;124)
    38.1 (29.4 to 47.5)
    49 (38.6 to 59.4)
    47.9 (36.1 to 60)
    43.5 (34.7 to 52.7)
        Anti-UspA2 (N=118;96;73;124)
    100 (96.9 to 100)
    100 (96.2 to 100)
    100 (95.1 to 100)
    100 (97.1 to 100)
    No statistical analyses for this end point

    Secondary: Percentage of subjects seropositive for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibodies, one-month post Dose-2 of NTHi-Mcat vaccine

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    End point title
    		 Percentage of subjects seropositive for Anti-PD, Anti-PE, Anti-PilA, Anti-UspA2 antibodies, one-month post Dose-2 of NTHi-Mcat vaccine [9]
    End point description
    A seropositive subject is defined as a subject whose Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibody concentrations are greater than or equal to the assay cut-off value. Seropositivity rates with 95% CI are defined using the assay (LLOQ). Cut-off value for the assay is 153, 16, 8 and 28 EU/mL for Anti-PD, Anti-PE, Anti-PilA and Anti-UspA2 antibodies respectively. Analysis was performed on the PPS which included all subjects who received full study treatment course to which they were randomized and had post-vaccination immunogenicity data minus subjects with protocol deviations that lead to exclusion. Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.
    End point type
    Secondary
    End point timeframe
    At one month after the second dose of NTHi-Mcat vaccine (Day 181, 241, 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    118
    96
    73
    124
    Units: Percentage of subjects
    number (confidence interval 95%)
        Anti-PD (N=118;96;73;123)
    99.2 (95.4 to 100)
    97.9 (92.7 to 99.7)
    100 (95.1 to 100)
    100 (97 to 100)
        Anti-PE (N=118;96;73;124)
    100 (96.9 to 100)
    100 (96.2 to 100)
    100 (95.1 to 100)
    100 (97.1 to 100)
        Anti-PilA (N=117;96;73;124)
    100 (96.9 to 100)
    100 (96.2 to 100)
    100 (95.1 to 100)
    100 (97.1 to 100)
        Anti-UspA2 (N=118;96;73;124)
    100 (96.9 to 100)
    100 (96.2 to 100)
    100 (95.1 to 100)
    100 (97.1 to 100)
    No statistical analyses for this end point

    Secondary: Frequency of specific Cluster of Differentiation 4 (CD4+) T-cells against NTHi and Mcat antigens for evaluation of cell-mediated immune (CMI) response, before first dose of NTHi-Mcat vaccine

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    End point title
    		 Frequency of specific Cluster of Differentiation 4 (CD4+) T-cells against NTHi and Mcat antigens for evaluation of cell-mediated immune (CMI) response, before first dose of NTHi-Mcat vaccine [10]
    End point description
    Frequency of specific CD4+ T-cells was measured by flow cytometry intracellular cytokine staining (ICS) expressing at least 2 different markers among CD40 Ligand (CD40L), interleukin (IL)-2, IL-13, IL-17, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), upon in vitro stimulation. Analysis was performed on Cell-Mediated immune (CMI) sub-cohort, which included approximately 60 subjects (15/each group), for which an additional blood sample was taken at each pre-defined timepoint (sub-cohort selected from sites able to process the blood samples according to GSK procedures for peripheral blood mononuclear cell preparation). Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.
    End point type
    Secondary
    End point timeframe
    Before the first dose of NTHi-Mcat vaccine (Day 91, Day 151 and Day 241 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 1 in the NTHi-Mcat group)
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    10
    12
    3
    13
    Units: CD4+ T cells/million cells
    arithmetic mean (standard deviation)
        M catarrhalis.UspA2 - CD4+ T-cells (N=10;12;3;13)
    112.945 ( 153.903 )
    101.739 ( 94.932 )
    81.578 ( 90.919 )
    92.685 ( 99.661 )
        NTHi.PD - CD4+ T-cells (N=10;12;3;13)
    89.456 ( 68.929 )
    59.522 ( 82.06 )
    36.439 ( 57.347 )
    96.893 ( 74.87 )
        NTHi.PE - CD4+ T-cells (N=10;12;3;13)
    79.838 ( 58.999 )
    46.112 ( 63.007 )
    69.546 ( 97.09 )
    80.717 ( 119.316 )
        NTHi.PilA - CD4+ T-cells (N=10;12;3;13)
    61.627 ( 53.613 )
    42.438 ( 55.575 )
    60.139 ( 51.37 )
    105.558 ( 97.618 )
    No statistical analyses for this end point

    Secondary: Frequency of CD4+ T-cells against NTHi and Mcat antigens for evaluation of CMI response, at one-month post dose 2 of NTHi-Mcat vaccine

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    End point title
    		 Frequency of CD4+ T-cells against NTHi and Mcat antigens for evaluation of CMI response, at one-month post dose 2 of NTHi-Mcat vaccine [11]
    End point description
    Frequency of specific CD4+ T-cells was measured by flow cytometry ICS expressing at least 2 different markers among CD40L, IL-2, IL-13, IL-17, TNF-α and IFN-γ, upon in vitro stimulation. Analysis was performed on CMI sub-cohort, which included approximately 60 subjects (15/each group), for which an additional blood sample was taken at each pre-defined time point (sub-cohort selected from sites able to process the blood samples according to GSK procedures for peripheral blood mononuclear cell preparation). Subjects from the Shingrix-Only Group were not included in this analysis, as they didn't receive the NTHi MCAT vaccine.
    End point type
    Secondary
    End point timeframe
    At one month after second dose of NTHi-Mcat vaccine (Day 181, Day 241 and Day 331 in the Sh_NTHi-Mcat_1, Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6 group, respectively, and Day 91 in the NTHi-Mcat group)
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    10
    11
    3
    13
    Units: CD4+ T cells/million cells
    arithmetic mean (standard deviation)
        M catarrhalis.UspA2 - CD4+ T-cells (N=10;11;3;13)
    721.851 ( 457.94 )
    619.68 ( 392.133 )
    1001.839 ( 144.057 )
    735.177 ( 471.515 )
        NTHi.PD - CD4+ T-cells (N=10;11;3;13)
    632.849 ( 323.731 )
    527.26 ( 281.827 )
    1570.631 ( 1064.327 )
    742.666 ( 527.567 )
        NTHi.PE - CD4+ T-cells (N=10;11;3;13)
    565.964 ( 411.715 )
    581.338 ( 520.594 )
    888.057 ( 154.524 )
    1155.341 ( 699.841 )
        NTHi.PilA - CD4+ T-cells (N=10;11;3;13)
    332.43 ( 273.215 )
    318.46 ( 195.527 )
    333.501 ( 121.712 )
    388.282 ( 207.434 )
    No statistical analyses for this end point

    Secondary: Percentage of subjects with reported solicited local adverse event (AE)

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    End point title
    		 Percentage of subjects with reported solicited local adverse event (AE) [12]
    End point description
    The percentage of subjects with at least one local solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed local symptoms were pain, redness and swelling. Any local injection site redness/swelling is scored as follows: diameter >=20 milli-meters. Analysis was performed on the Solicited safety set (SSS) which included all subjects who received at least 1 dose of the study treatment and who have solicited safety data.
    End point type
    Secondary
    End point timeframe
    During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    134
    133
    118
    135
    Units: Percentage of subjects
    number (confidence interval 95%)
        Erythema (mm), Dose 1 (N=134;133;118;135)
    6 (2.6 to 11.4)
    15 (9.4 to 22.3)
    11 (6 to 18.1)
    12.6 (7.5 to 19.4)
        Erythema (mm), Dose 2 (N=133;131;117;127)
    12.8 (7.6 to 19.7)
    13.7 (8.4 to 20.8)
    17.9 (11.5 to 26.1)
    11.8 (6.8 to 18.7)
        Pain, Dose 1 (N=134;133;118;135)
    59.7 (50.9 to 68.1)
    69.2 (60.6 to 76.9)
    61 (51.6 to 69.9)
    63.7 (55 to 71.8)
        Pain, Dose 2 (N=133;131;117;127)
    69.9 (61.4 to 77.6)
    76.3 (68.1 to 83.3)
    72.6 (63.6 to 80.5)
    75.6 (67.2 to 82.8)
        Swelling (mm), Dose 1 (N=134;133;118;135)
    3.7 (1.2 to 8.5)
    10.5 (5.9 to 17)
    5.9 (2.4 to 11.8)
    5.2 (2.1 to 10.4)
        Swelling (mm), Dose 2 (N=133;131;117;127)
    7.5 (3.7 to 13.4)
    8.4 (4.3 to 14.5)
    6.8 (3 to 13)
    7.9 (3.8 to 14)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with reported solicited general AE

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    End point title
    		 Percentage of subjects with reported solicited general AE [13]
    End point description
    The percentage of subjects with at least one general solicited AE, regardless of intensity, during the 7-day follow-up period after each NTHi-Mcat vaccine dose, are reported by study group. Assessed solicited general symptoms were Fatigue, Gastrointestinal symptoms (nausea, vomiting, diarrhoea and/or abdominal pain), Headache, Myalgia, Chills and Fever (oral cavity or axillary route - temperature equal or higher than [>=] 37.5 degrees Celsius [°C]). Analysis was performed on the SSS which included all subjects who received at least 1 dose of the study treatment and who have solicited safety data.
    End point type
    Secondary
    End point timeframe
    During the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    134
    133
    118
    135
    Units: Percentage of subjects
    number (confidence interval 95%)
        Chills, Dose 1 (N=134;133;118;35)
    11.9 (7 to 18.7)
    12 (7 to 18.8)
    16.9 (10.7 to 25)
    7.4 (3.6 to 13.2)
        Chills, Dose 2 (N=133;131;117;127)
    25.6 (18.4 to 33.8)
    26 (18.7 to 34.3)
    22.2 (15.1 to 30.8)
    16.5 (10.5 to 24.2)
        Fatigue, Dose 1 (N=134;133;118;135)
    26.1 (18.9 to 34.4)
    38.3 (30.1 to 47.2)
    39 (30.1 to 48.4)
    34.1 (26.1 to 42.7)
        Fatigue, Dose 2 (N=133;131;117;127)
    39.1 (30.8 to 47.9)
    48.1 (39.3 to 57)
    43.6 (34.4 to 53.1)
    37.8 (29.3 to 46.8)
        Fever (C), Dose 1 (N=134;133;18;135)
    1.5 (0.2 to 5.3)
    1.5 (0.2 to 5.3)
    2.5 (0.5 to 7.3)
    3 (0.8 to 7.4)
        Fever (C), Dose 2 (N=133;131;117;127)
    11.3 (6.5 to 17.9)
    8.4 (4.3 to 14.5)
    8.5 (4.2 to 15.2)
    8.7 (4.4 to 15)
        Gastrointest. symptoms, Dose 1 (N=134;133;118;135)
    13.4 (8.2 to 20.4)
    13.5 (8.2 to 20.5)
    16.1 (10 to 24)
    13.3 (8.1 to 20.3)
        Gastrointest. symptoms, Dose 2 (N=133;131;117;127)
    15.8 (10 to 23.1)
    15.3 (9.6 to 22.6)
    12.8 (7.4 to 20.3)
    9.4 (5 to 15.9)
        Headache, Dose 1 (N=134;133;118;135)
    20.9 (14.4 to 28.8)
    26.3 (19.1 to 34.7)
    22.9 (15.7 to 31.5)
    18.5 (12.4 to 26.1)
        Headache, Dose 2 (N=133;131;117;127)
    32.3 (24.5 to 41)
    38.2 (29.8 to 47.1)
    23.9 (16.5 to 32.7)
    22 (15.2 to 30.3)
        Myalgia, Dose 1 (N=134;133;118;135)
    20.1 (13.7 to 27.9)
    23.3 (16.4 to 31.4)
    25.4 (17.9 to 34.3)
    27.4 (20.1 to 35.7)
        Myalgia, Dose 2 (N=133;131;117;127)
    33.1 (25.2 to 41.8)
    37.4 (29.1 to 46.3)
    36.8 (28 to 46.2)
    37.8 (29.3 to 46.8)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with any unsolicited AE

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    End point title
    		 Percentage of subjects with any unsolicited AE [14]
    End point description
    An unsolicited adverse event is an adverse event that was not solicited using a Subject Diary and that was spontaneously communicated by a subject who has signed the informed consent. The percentage of subjects with at least one unsolicited AE, regardless of intensity or relationship to vaccination, during the 30-day follow-up period after any NTHi-Mcat vaccine dose are reported for each group. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event. Analysis was performed on the Unsolicited safety set which included all subjects who receive at least 1 dose of the study treatment and who have unsolicited safety data.
    End point type
    Secondary
    End point timeframe
    During the 30-day follow-up period (i.e. day of vaccination and 29 subsequent days) after Dose 1 and after Dose 2 of NTHi-Mcat vaccine
    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 outcome was descriptive; hence no statistical analyses were required.
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group
    Number of subjects analysed
    134
    134
    122
    135
    Units: Percentage of subjects
    number (confidence interval 95%)
        Dose 1 (N=134;134;122;135)
    13.4 (8.2 to 20.4)
    14.9 (9.4 to 22.1)
    11.5 (6.4 to 18.5)
    18.5 (12.4 to 26.1)
        Dose 2 (N=133;131;118;129)
    15 (9.4 to 22.3)
    15.3 (9.6 to 22.6)
    8.5 (4.1 to 15)
    10.9 (6.1 to 17.5)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with any serious adverse event (SAE) during Epoch 001

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    End point title
    		 Percentage of subjects with any serious adverse event (SAE) during Epoch 001
    End point description
    The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 1 up to and including Day 331, were reported for each group An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject or was a congenital anomaly/birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician. Analysis was performed on the Exposed Set (ES) which included all subjects who received at least 1 dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to and including Day 331 (Epoch 001)
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group Shingrix-Only Group
    Number of subjects analysed
    134
    134
    122
    135
    16
    Units: Percentage of subjects
        number (confidence interval 95%)
    4.5 (1.7 to 9.5)
    3.7 (1.2 to 8.5)
    2.5 (0.5 to 7)
    1.5 (0.2 to 5.2)
    6.3 (0.2 to 30.2)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with any Potential Immune-mediated diseases (pIMD's) during Epoch 001

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    End point title
    		 Percentage of subjects with any Potential Immune-mediated diseases (pIMD's) during Epoch 001
    End point description
    pIMD's are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Analysis was performed on the ES which included all subjects who received at least 1 dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    From Day 1 up to and including Day 331 (Epoch 001)
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group Shingrix-Only Group
    Number of subjects analysed
    134
    134
    122
    135
    16
    Units: Percentage of subjects
        number (confidence interval 95%)
    0 (0 to 2.7)
    1.5 (0.2 to 5.3)
    0.8 (0 to 4.5)
    0 (0 to 2.7)
    12.5 (1.6 to 38.3)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with any SAE during Epoch 002

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    End point title
    		 Percentage of subjects with any SAE during Epoch 002
    End point description
    The percentage of subjects with at least one SAE, regardless of intensity or relationship to vaccination, from Day 332 up to and including Day 661, are reported for each group. An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, requires hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject or was a congenital anomaly/birth defect in the offspring of a study subject. AE(s) considered as SAE(s) also include invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, as per the medical or scientific judgement of the physician. Analysis was performed on the ES which included all subjects who received at least 1 dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    From Day 332 up to and including Day 661 (Epoch 002)
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group Shingrix-Only Group
    Number of subjects analysed
    134
    134
    122
    135
    16
    Units: Percentage of subjects
        number (confidence interval 95%)
    3.0 (0.8 to 7.5)
    4.5 (1.7 to 9.5)
    3.3 (0.9 to 8.2)
    2.2 (0.5 to 6.4)
    0.0 (0.0 to 20.6)
    No statistical analyses for this end point

    Secondary: Percentage of subjects with any pIMD's during Epoch 002

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    End point title
    		 Percentage of subjects with any pIMD's during Epoch 002
    End point description
    pIMD's are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Analysis was performed on the ES which included all subjects who received at least 1 dose of the study treatment.
    End point type
    Secondary
    End point timeframe
    From Day 332 up to and including Day 661 (Epoch 002)
    End point values
    		 Sh_NTHi-Mcat_1 Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group NTHi-Mcat Group Shingrix-Only Group
    Number of subjects analysed
    134
    134
    122
    135
    16
    Units: Percentage of subjects
        number (confidence interval 95%)
    0.7 (0.0 to 4.1)
    0.7 (0.0 to 4.1)
    0.0 (0.0 to 3.0)
    0.0 (0.0 to 2.7)
    0.0 (0.0 to 20.6)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited adverse events were collected during the 7-day follow-up period and unsolicited adverse events during the 30-day follow-up period. Serious adverse events were collected from Day 1 up to Day 661.
    Adverse event reporting additional description
    Other Adverse events were not collected for Shingrix-Only Group.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Sh_NTHi-Mcat_1 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, and following a 1-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 91, and Day 151.

    Reporting group title
    Shingrix-Only Group
    Reporting group description
    		 Subjects enrolled in this group received at least 1, maximum 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61, but didn't receive any dose of NTHI Mcat investigational vaccine.

    Reporting group title
    NTHi-Mcat Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 1 and Day 61.

    Reporting group title
    Sh_NTHi-Mcat_3 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 3-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart, at Day 151 and Day 211.

    Reporting group title
    Sh_NTHi-Mcat_6 Group
    Reporting group description
    		 Subjects enrolled in this group received 2 doses of GSK Biologicals' Shingrix vaccine at Day 1 and Day 61 and, following a 6-month gap, subjects received 2 doses of GSK Biological's NTHi-Mcat investigational vaccine 2 months apart at Day 241 and Day 301.

    Serious adverse events
    		 Sh_NTHi-Mcat_1 Group Shingrix-Only Group NTHi-Mcat Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 134 (6.72%)
    1 / 16 (6.25%)
    5 / 135 (3.70%)
    11 / 134 (8.21%)
    6 / 122 (4.92%)
         number of deaths (all causes)
    0
    0
    0
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 134 (0.00%)
    1 / 16 (6.25%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoma
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    2 / 134 (1.49%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenoma
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery restenosis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic rupture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Embolism venous
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Giant cell arteritis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    2 / 122 (1.64%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ruptured cerebral aneurysm
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cognitive disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular hole
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin necrosis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus urinary
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Polymyalgia rheumatica
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary tuberculosis, unspecified
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Sh_NTHi-Mcat_1 Group Shingrix-Only Group NTHi-Mcat Group Sh_NTHi-Mcat_3 Group Sh_NTHi-Mcat_6 Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    118 / 134 (88.06%)
    0 / 16 (0.00%)
    125 / 135 (92.59%)
    125 / 134 (93.28%)
    107 / 122 (87.70%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Surgical and medical procedures
    Dental implantation
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    2 / 122 (1.64%)
         occurrences all number
    0
    0
    0
    0
    2
    Chest discomfort
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    1
    0
    1
    Chills
         subjects affected / exposed
    40 / 134 (29.85%)
    0 / 16 (0.00%)
    26 / 135 (19.26%)
    41 / 134 (30.60%)
    40 / 122 (32.79%)
         occurrences all number
    50
    0
    31
    50
    47
    Feeling hot
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    63 / 134 (47.01%)
    0 / 16 (0.00%)
    65 / 135 (48.15%)
    78 / 134 (58.21%)
    68 / 122 (55.74%)
         occurrences all number
    88
    0
    95
    114
    99
    Discomfort
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Hangover
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    1
    0
    0
    0
    1
    Injection site erythema
         subjects affected / exposed
    21 / 134 (15.67%)
    0 / 16 (0.00%)
    24 / 135 (17.78%)
    27 / 134 (20.15%)
    28 / 122 (22.95%)
         occurrences all number
    25
    0
    32
    38
    34
    Injection site movement impairment
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Injection site pain
         subjects affected / exposed
    105 / 134 (78.36%)
    0 / 16 (0.00%)
    112 / 135 (82.96%)
    112 / 134 (83.58%)
    98 / 122 (80.33%)
         occurrences all number
    173
    0
    182
    192
    157
    Injection site pruritus
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Injection site swelling
         subjects affected / exposed
    12 / 134 (8.96%)
    0 / 16 (0.00%)
    15 / 135 (11.11%)
    19 / 134 (14.18%)
    13 / 122 (10.66%)
         occurrences all number
    15
    0
    17
    25
    15
    Malaise
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    16 / 134 (11.94%)
    0 / 16 (0.00%)
    14 / 135 (10.37%)
    12 / 134 (8.96%)
    13 / 122 (10.66%)
         occurrences all number
    17
    0
    15
    13
    13
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Catarrh
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Asthmatic crisis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dyspnoea
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dysphonia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nasal congestion
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    3 / 134 (2.24%)
    0 / 16 (0.00%)
    2 / 135 (1.48%)
    1 / 134 (0.75%)
    1 / 122 (0.82%)
         occurrences all number
    3
    0
    2
    1
    1
    Productive cough
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Investigations
    Weight increased
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    1
    0
    1
    Ligament rupture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Fall
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Head injury
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Joint dislocation
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Muscle rupture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Lower limb fracture
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Thermal burn
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tibia fracture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Cardiac disorders
    Extrasystoles
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Dizziness
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    56 / 134 (41.79%)
    0 / 16 (0.00%)
    42 / 135 (31.11%)
    66 / 134 (49.25%)
    44 / 122 (36.07%)
         occurrences all number
    78
    0
    56
    92
    59
    Somnolence
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Syncope
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    2
    0
    0
    Ear pruritus
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Vertigo
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Eye disorders
    Blepharospasm
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Chalazion
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eye pain
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Eyelid ptosis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Swelling of eyelid
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Constipation
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    3 / 134 (2.24%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Dyspepsia
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Diarrhoea
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Gastrointestinal disorder
         subjects affected / exposed
    34 / 134 (25.37%)
    0 / 16 (0.00%)
    26 / 135 (19.26%)
    32 / 134 (23.88%)
    26 / 122 (21.31%)
         occurrences all number
    39
    0
    30
    38
    34
    Nausea
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tooth disorder
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Toothache
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    2 / 122 (1.64%)
         occurrences all number
    1
    0
    0
    1
    2
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Eczema
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Pain of skin
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    2 / 135 (1.48%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Rash
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    1 / 134 (0.75%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    1
    1
    1
    Psoriasis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Endocrine disorders
    Basedow's disease
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 134 (1.49%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    3 / 134 (2.24%)
    0 / 122 (0.00%)
         occurrences all number
    2
    0
    1
    3
    0
    Arthritis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Back pain
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    3 / 135 (2.22%)
    1 / 134 (0.75%)
    1 / 122 (0.82%)
         occurrences all number
    1
    0
    3
    1
    1
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Muscle contracture
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    1
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Neck pain
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    3 / 134 (2.24%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    4
    0
    Myalgia
         subjects affected / exposed
    48 / 134 (35.82%)
    0 / 16 (0.00%)
    67 / 135 (49.63%)
    64 / 134 (47.76%)
    56 / 122 (45.90%)
         occurrences all number
    73
    0
    87
    80
    76
    Osteoarthritis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Tendonitis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Infections and infestations
    Bacterial vaginosis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Cystitis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    0
    1
    Bronchitis
         subjects affected / exposed
    3 / 134 (2.24%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    3
    0
    0
    1
    0
    Dengue fever
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    3 / 134 (2.24%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    3 / 134 (2.24%)
    2 / 122 (1.64%)
         occurrences all number
    3
    0
    0
    3
    2
    Influenza
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Herpes simplex
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Genital herpes
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Pulpitis dental
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    1 / 122 (0.82%)
         occurrences all number
    1
    0
    0
    0
    1
    Otitis media
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    3 / 135 (2.22%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    3
    1
    0
    Schistosomiasis cutaneous
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    2 / 135 (1.48%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    1 / 122 (0.82%)
         occurrences all number
    0
    0
    0
    1
    1
    Tooth abscess
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    1 / 135 (0.74%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Viral infection
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    3 / 135 (2.22%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 134 (0.00%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    1 / 134 (0.75%)
    0 / 122 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Metabolism and nutrition disorders
    Metabolic syndrome
         subjects affected / exposed
    1 / 134 (0.75%)
    0 / 16 (0.00%)
    0 / 135 (0.00%)
    0 / 134 (0.00%)
    0 / 122 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 May 2020
    •The current analysis of the primary objective is planned on the per protocol population. The use of the per protocol defined windows for vaccination and blood draws minimizes potential variability within the data for statistical comparisons. To control the type I error below 2.5% (one-sided), a sequential procedure is planned in the protocol. Starting from the 6-months lag, the 3-months NI will be tested only if the 6-months NI will be demonstrated, while the 1-month NI will be tested only if the 6-months and 3-months NI will be both demonstrated. •The study started on 23 Apr 2019. At the time of writing, group Sh_NTHi-Mcat_1 and control group NTHi-Mcat have completed the vaccination schedule and the blood draw as dictated by the study protocol, whereas the less advanced groups (Sh_NTHi-Mcat_3 and Sh_NTHi-Mcat_6) are either due to receive the study vaccine or to undergo a blood draw. In accordance with the safety measures applied for COVID-19 containment in the countries where the study is conducted, a number of study visits are unlikely to occur as planned. This is expected to impact 2 of the study groups (Sh_NTHi-Mcat_3 and Sh_NTHi Mcat_6). •The amendment includes a modified primary objective, should the Sh-NTHi-Mcat_6 or the Sh-NTHi-Mcat_3 and Sh_NTHi-Mcat_3 groups not meet the per-protocol defined sample size. •This amendment also outlines measures (e.g. for safety monitoring) that may be applicable during special circumstances, like COVID-19 pandemic. •Provisions relating to specific reporting of serious adverse events and serious adverse reactions, in accordance with Article R1123-54 and Article R1123-46 of the French Public Health Code, are incorporated into the "Requirements for France” Section of this Protocol Amendment. •Other minor changes have been made to correct typos and improve clarity and alignment within the document.

    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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