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    Clinical Trial Results:
    A Phase III, randomised, observer-blind, placebo-controlled, multicentre study to assess the safety, immunogenicity and efficacy of GSK Biologicals’ Herpes Zoster HZ/su candidate vaccine when administered intramuscularly on a two-dose schedule to adults aged 18 years and older with haematologic malignancies.

    Summary
    EudraCT number
    		 2012-003438-18
    Trial protocol
    		 SE   BE   FI   ES   IT   CZ   GB   PL  
    Global end of trial date
    06 Jan 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Jan 2018
    First version publication date
    03 Jan 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    116428
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01767467
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, 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
    27 Oct 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jan 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • To evaluate the safety and tolerability following administration of the HZ/su vaccine compared to placebo from the first vaccination up to 30 days post last vaccination in subjects with haematologic malignancies, aged 18 years and older. • To evaluate vaccine response rate (VRR) for anti-glycoprotein E (anti-gE) humoral immune responses at Month 2 following a two-dose administration of the HZ/su vaccine in subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia. • To evaluate anti-gE humoral immune responses at Month 2 following a two-dose administration of the HZ/su vaccine, as compared to placebo, in subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.
    Protection of trial subjects
    All subjects were supervised after vaccination/product administration with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Mar 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 29
    Country: Number of subjects enrolled
    Belgium: 31
    Country: Number of subjects enrolled
    Canada: 23
    Country: Number of subjects enrolled
    Czech Republic: 13
    Country: Number of subjects enrolled
    Finland: 10
    Country: Number of subjects enrolled
    France: 28
    Country: Number of subjects enrolled
    Hong Kong: 3
    Country: Number of subjects enrolled
    Italy: 23
    Country: Number of subjects enrolled
    Korea, Republic of: 107
    Country: Number of subjects enrolled
    New Zealand: 11
    Country: Number of subjects enrolled
    Pakistan: 12
    Country: Number of subjects enrolled
    Panama: 14
    Country: Number of subjects enrolled
    Poland: 31
    Country: Number of subjects enrolled
    Russian Federation: 27
    Country: Number of subjects enrolled
    Singapore: 1
    Country: Number of subjects enrolled
    Spain: 64
    Country: Number of subjects enrolled
    Sweden: 26
    Country: Number of subjects enrolled
    Taiwan: 29
    Country: Number of subjects enrolled
    Turkey: 52
    Country: Number of subjects enrolled
    United Kingdom: 48
    Country: Number of subjects enrolled
    United States: 24
    Worldwide total number of subjects
    606
    EEA total number of subjects
    274
    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)
    370
    From 65 to 84 years
    219
    85 years and over
    17

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Out of the 568 subjects enrolled, only 562 subjects received vaccination as per protocol and hence started the study.

    Pre-assignment period milestones
    Number of subjects started
    		 606
    Number of subjects completed
    		 562

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Study vaccine dose not administered AT ALL but sub: 44
    Period 1
    Period 1 title
    Vaccination Phase (up to Month 2)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind [1]
    Roles blinded
    		 Subject, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK1437173A Group
    Arm description
    		 Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Herpes Zoster vaccine GSK1437173A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Administered according to a 0, 1 Months schedule (The second dose of study vaccine/placebo could be administered 1 - 2 months after the first dose)

    Arm title
    		 Placebo Group
    Arm description
    		 Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Administered according to a 0, 1 Months schedule (The second dose of study vaccine/placebo could be administered 1 - 2 months after the first dose)

    Notes
    [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial.
    Justification: The blinding was presented as per the protocol.
    Number of subjects in period 1 [2]
    		GSK1437173A Group Placebo Group
    Started
    283
    279
    Completed
    266
    259
    Not completed
    17
    20
         Consent withdrawn by subject
    7
    10
         Physician decision
    1
    -
         Adverse event, non-fatal
    8
    8
         Subject Unavailable
    -
    1
         Suspected Herpes Zoster episode
    -
    1
         Protocol deviation
    1
    -
    Notes
    [2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of the enrolled subjects, some received subject numbers but did not receive the study vaccination, hence they were excluded from study start.
    Period 2
    Period 2 title
    End of Study Phase (up to Month 13)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind [3]
    Roles blinded
    		 Subject, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK1437173A Group
    Arm description
    		 Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Herpes Zoster vaccine GSK1437173A
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Administered according to a 0, 1 Months schedule (The second dose of study vaccine/placebo could be administered 1 - 2 months after the first dose)

    Arm title
    		 Placebo Group
    Arm description
    		 Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose).
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solution for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Administered according to a 0, 1 Months schedule (The second dose of study vaccine/placebo could be administered 1 - 2 months after the first dose)

    Notes
    [3] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial.
    Justification: The blinding was presented as per the protocol.
    Number of subjects in period 2
    		GSK1437173A Group Placebo Group
    Started
    266
    259
    Completed
    236
    216
    Not completed
    30
    43
         Consent withdrawn by subject
    2
    4
         Migrated/Moved from study area
    -
    3
         Adverse event, non-fatal
    21
    31
         Subject Unavailable
    -
    1
         Lost to follow-up
    6
    4
         Protocol deviation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK1437173A Group
    Reporting group description
    		 Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose).

    Reporting group title
    Placebo Group
    Reporting group description
    		 Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose).

    Reporting group values
    		 GSK1437173A Group Placebo Group Total
    Number of subjects
    		 283 279
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56.8 ( 15.5 ) 57.8 ( 14.9 ) -
    Gender categorical
    Units: Subjects
        Female
    		 114 114 228
        Male
    		 169 165 334
    Race/Ethnicity, Customized
    Units: Subjects
        African Heritage / African American
    		 1 1 2
        American Indian or Alaskan Native
    		 0 1 1
        Asian - Central / South Asian Heritage
    		 5 6 11
        Asian - East Asian Heritage
    		 57 60 117
        Asian - South East Asian Heritage
    		 4 1 5
        White - Arabic / North African Heritage
    		 0 1 1
        White - Caucasian / European Heritage
    		 198 186 384
        Other
    		 7 12 19
        Missing
    		 11 11 22

    End points

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    End points reporting groups
    Reporting group title
    GSK1437173A Group
    Reporting group description
    		 Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose).

    Reporting group title
    Placebo Group
    Reporting group description
    		 Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose).
    Reporting group title
    GSK1437173A Group
    Reporting group description
    		 Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose).

    Reporting group title
    Placebo Group
    Reporting group description
    		 Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose).

    Subject analysis set title
    GSK1437173A HZ cases Sub-Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose), with confirmed Herpes Zoster (HZ).

    Subject analysis set title
    GSK1437173A Non-HZ cases Sub-Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose), with non-confirmed Herpes Zoster (HZ).

    Subject analysis set title
    Placebo HZ cases Sub-Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose), with confirmed Herpes Zoster (HZ).

    Subject analysis set title
    Placebo Non-HZ cases Sub-Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose), with non-confirmed Herpes Zoster (HZ).

    Primary: Vaccine response rates (VRR) for anti-glycoprotein E (anti-gE) antibody concentrations

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    End point title
    		 Vaccine response rates (VRR) for anti-glycoprotein E (anti-gE) antibody concentrations [1]
    End point description
    Vaccine response rate refers to the percentage of subjects with a vaccine response, as determined by Enzyme-Linked Immunosorbent Assay (ELISA). Vaccine response was defined as: For initially seronegative subjects, antibody concentration at Month 2 greater than or equal to (≥) 4 fold the cut-off for Anti-gE [4x97 milli-international units per milliliter (mIU/mL)]. For initially seropositive subjects, antibody concentration at Month 2 ≥ 4 fold the pre-vaccination antibody concentration. This analysis was performed on subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.
    End point type
    Primary
    End point timeframe
    At Month 2
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    148
    130
    Units: Percentage
    number (confidence interval 95%)
        Percentage
    80.4 (73.1 to 86.5)
    0.8 (0.0 to 4.2)
    No statistical analyses for this end point

    Primary: Adjusted geometric mean concentration of anti-gE antibodies

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    End point title
    		 Adjusted geometric mean concentration of anti-gE antibodies
    End point description
    The Adjusted geometric mean concentration was measured in all subjects excluding those with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.
    End point type
    Primary
    End point timeframe
    At Month 2
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    148
    130
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        mIU/mL
    22132.9 (16642.8 to 32153.9)
    777.6 (702.8 to 860.3)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    The objective aimed to evaluate anti-gE humoral immune responses at Month 2 following a two-dose administration of the GSK1437173A vaccine, as compared to placebo, in subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia.
    Comparison groups
    Placebo Group v GSK1437173A Group
    Number of subjects included in analysis
    278
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    P-value
    		 < 0.0001 [3]
    Method
    		 Repeated measurement model
    Parameter type
    		 Adjusted Geometric Mean Concentration
    Point estimate
    29.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 21.09
         upper limit
    		 41.96
    Notes
    [2] - The objective was met if the lower limit of the 95% CI of the Geometric Mean (GM) ratio (GSK1437173A vaccine over placebo) for anti-gE ELISA antibody concentrations at Month 2 was greater than (>) 3.
    [3] - The p-value is relative to the null hypothesis Ho: Vaccine / Placebo = 1

    Primary: Number of subjects with any and Grade 3 solicited local symptoms

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    End point title
    		 Number of subjects with any and Grade 3 solicited local symptoms [4]
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
    End point type
    Primary
    End point timeframe
    During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    278
    274
    Units: Participants
        Any Pain, Dose 1
    199
    26
        Grade 3 Pain, Dose 1
    16
    0
        Any Redness, Dose 1
    80
    1
        Grade 3 Redness, Dose 1
    2
    0
        Any Swelling, Dose 1
    47
    2
        Grade 3 Swelling, Dose 1
    1
    0
        Any Pain, Dose 2
    172
    31
        Grade 3 Pain, Dose 2
    20
    0
        Any Redness, Dose 2
    82
    5
        Grade 3 Redness, Dose 2
    10
    0
        Any Swelling, Dose 2
    42
    1
        Grade 3 Swelling, Dose 2
    5
    0
        Any Pain, Across doses
    221
    45
        Grade 3 Pain, Across doses
    29
    0
        Any Redness, Across doses
    115
    5
        Grade 3 Redness, Across doses
    12
    0
        Any Swelling, Across doses
    63
    2
        Grade 3 Swelling, Across doses
    5
    0
    No statistical analyses for this end point

    Primary: Number of days with solicited local symptoms

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    End point title
    		 Number of days with solicited local symptoms [5]
    End point description
    Solicited local symptoms: pain, redness, swelling and their number of days were recorded after each vaccination dose.
    End point type
    Primary
    End point timeframe
    Within the 7-day (Days 0-6) post-vaccination period
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    278
    271
    Units: Days
    median (inter-quartile range (Q1-Q3))
        Pain, Dose 1
    3.0 (2.0 to 4.0)
    1.0 (1.0 to 2.0)
        Pain, Dose 2
    3.0 (2.0 to 4.0)
    2.0 (1.0 to 3.0)
        Redness, Dose 1
    3.0 (2.0 to 5.0)
    1.0 (1.0 to 1.0)
        Redness, Dose 2
    3.0 (2.0 to 5.0)
    4.0 (2.0 to 6.0)
        Swelling, Dose 1
    3.0 (2.0 to 4.0)
    1.5 (1.0 to 2.0)
        Swelling, Dose 2
    3.0 (2.0 to 4.0)
    4.0 (4.0 to 4.0)
    No statistical analyses for this end point

    Primary: Number of subjects with any, Grade 3 and related solicited general symptoms

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    End point title
    		 Number of subjects with any, Grade 3 and related solicited general symptoms [6]
    End point description
    Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), headache, myalgia, shivering and fever [defined as oral, axillary or tympanic route measured temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
    End point type
    Primary
    End point timeframe
    During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    278
    274
    Units: Participants
        Any fatigue, Dose 1
    122
    73
        Grade 3 fatigue, Dose 1
    11
    8
        Related fatigue, Dose 1
    37
    11
        Any gastrointestinal, Dose 1
    48
    24
        Grade 3 gastrointestinal, Dose 1
    5
    2
        Related gastrointestinal, Dose 1
    13
    1
        Any headache, Dose 1
    70
    40
        Grade 3 headache, Dose 1
    3
    3
        Related headache, Dose 1
    29
    10
        Any myalgia, Dose 1
    80
    35
        Grade 3 myalgia, Dose 1
    11
    0
        Related myalgia, Dose 1
    33
    10
        Any shivering, Dose 1
    39
    16
        Grade 3 shivering, Dose 1
    2
    0
        Related shivering, Dose 1
    14
    2
        Any temperature, Dose 1
    33
    15
        Grade 3 temperature, Dose 1
    0
    1
        Related temperature, Dose 1
    18
    3
        Any fatigue, Dose 2
    126
    67
        Grade 3 fatigue, Dose 2
    16
    6
        Related fatigue, Dose 2
    49
    13
        Any gastrointestinal, Dose 2
    53
    16
        Grade 3 gastrointestinal, Dose 2
    5
    2
        Related gastrointestinal, Dose 2
    20
    4
        Any headache, Dose 2
    90
    42
        Grade 3 headache, Dose 2
    10
    3
        Related headache, Dose 2
    42
    9
        Any myalgia, Dose 2
    93
    25
        Grade 3 myalgia, Dose 2
    14
    5
        Related myalgia, Dose 2
    50
    7
        Any shivering, Dose 2
    48
    7
        Grade 3 shivering, Dose 2
    9
    0
        Related shivering, Dose 2
    27
    1
        Any temperature, Dose 2
    51
    11
        Grade 3 teamperature, Dose 2
    3
    0
        Related temperature, Dose 2
    28
    3
        Any fatigue, Across doses
    162
    102
        Grade 3 fatigue, Across doses
    23
    10
        Related fatigue, Across doses
    63
    22
        Any gastrointestinal, Across doses
    76
    29
        Grade 3 gastrointestinal, Across doses
    9
    3
        Related gastrointestinal, Across doses
    28
    5
        Any headache, Across doses
    115
    64
        Grade 3 headache, Across doses
    12
    6
        Related headache, Across doses
    52
    16
        Any myalgia, Across doses
    122
    48
        Grade 3 myalgia, Across doses
    22
    5
        Related myalgia, Across doses
    63
    15
        Any shivering, Across doses
    69
    18
        Grade 3 shivering, Across doses
    11
    0
        Related shivering, Across doses
    36
    2
        Any temperature, Across doses
    68
    21
        Grade 3 temperature, Across doses
    3
    1
        Related teamperature, Across doses
    36
    4
    No statistical analyses for this end point

    Primary: Number of days with solicited general symptoms

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    End point title
    		 Number of days with solicited general symptoms [7]
    End point description
    Solicited general symptoms: fatigue, gastrointestinal symptoms, headache, myalgia, shivering, temperature and their number of days were recorded after each vaccination dose.
    End point type
    Primary
    End point timeframe
    Withing the 7-day (Day 0-6) post-vaccination period
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    278
    271
    Units: Days
    median (inter-quartile range (Q1-Q3))
        Fatigue, Dose 1
    3.0 (1.0 to 6.0)
    3.0 (2.0 to 7.0)
        Fatigue, Dose 2
    3.0 (2.0 to 5.0)
    3.0 (1.0 to 7.0)
        Gastrointestinal symptoms, Dose 1
    2.5 (1.0 to 5.0)
    3.5 (1.5 to 6.0)
        Gastrointestinal symptoms, Dose 2
    2.0 (1.0 to 3.0)
    6.0 (2.5 to 7.0)
        Headache, Dose 1
    2.0 (1.0 to 3.0)
    1.5 (1.0 to 3.0)
        Headache, Dose 2
    2.0 (1.0 to 3.0)
    1.0 (1.0 to 3.0)
        Myalgia, Dose 1
    3.5 (2.0 to 5.5)
    3.0 (1.0 to 4.0)
        Myalgia, Dose 2
    2.0 (2.0 to 4.0)
    3.0 (1.0 to 7.0)
        Shivering, Dose 1
    2.0 (1.0 to 3.0)
    2.0 (1.0 to 3.5)
        Shivering, Dose 2
    1.0 (1.0 to 2.0)
    4.0 (2.0 to 4.0)
        Temperature, Dose 1
    1.0 (1.0 to 2.0)
    2.0 (1.0 to 3.0)
        Temperature, Dose 2
    1.0 (1.0 to 2.0)
    2.0 (1.0 to 4.0)
    No statistical analyses for this end point

    Primary: Number of subjects with any, Grade 3 and related unsolicited adverse events (AEs)

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    End point title
    		 Number of subjects with any, Grade 3 and related unsolicited adverse events (AEs) [8]
    End point description
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study. It also included any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
    End point type
    Primary
    End point timeframe
    Within the 30-day (Days 0-29) post-vaccination period
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    283
    279
    Units: Participants
        Any AEs
    134
    128
        Grade 3 AEs
    25
    28
        Related AEs
    19
    5
    No statistical analyses for this end point

    Primary: Number of subjects with serious adverse events (SAEs)

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    End point title
    		 Number of subjects with serious adverse events (SAEs) [9]
    End point description
    A Serious adverse event (SAE) is any untoward medical occurrence that result in death, is life threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject. Related = SAEs assessed by the investigator as causally related to the study vaccination
    End point type
    Primary
    End point timeframe
    From first vaccination up to 30 days post last vaccination
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    283
    279
    Units: Participants
        At least one SAE
    17
    29
        Related SAEs
    0
    0
    No statistical analyses for this end point

    Primary: Number of subjects reporting any and related potential immune-mediated diseases (pIMDs)

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    End point title
    		 Number of subjects reporting any and related potential immune-mediated diseases (pIMDs) [10]
    End point description
    Potential immune-mediated diseases (pIMDs) 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. Related = pIMds assessed by the investigator as causally related to the study vaccination
    End point type
    Primary
    End point timeframe
    From first vaccination up to 30 days post last vaccination
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint was descriptive, hence no statistical anaylses were performed.
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    283
    279
    Units: Participants
        Any pIMDs
    1
    0
        Related pIMDs
    0
    0
    No statistical analyses for this end point

    Secondary: Vaccine response rate (VRR) for anti-gE antibody concentrations

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    End point title
    		 Vaccine response rate (VRR) for anti-gE antibody concentrations
    End point description
    Vaccine response rate refers to the percentage of subjects with a vaccine response, as determined by ELISA. Vaccine response was defined as: For initially seronegative subjects, antibody concentration at Month 2 ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/mL). For initially seropositive subjects, antibody concentration at Month 2 ≥ 4 fold the pre -vaccination antibody concentration. This analysis was performed on subjects with haematologic malignancies, excluding subjects with Non-Hodgkin B-cell Lymphoma.
    End point type
    Secondary
    End point timeframe
    At Month 2
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    184
    165
    Units: Percentage
    number (confidence interval 95%)
        Percentage
    69.0 (61.8 to 75.6)
    0.6 (0.0 to 3.3)
    No statistical analyses for this end point

    Secondary: Anti-gE antibody concentrations

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    End point title
    		 Anti-gE antibody concentrations
    End point description
    Antibody concentrations were determined by ELISA, presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).This parameter was assessed in subjects with haematologic malignancies, excluding subjects with Non-Hodgkin B-cell Lymphoma.
    End point type
    Secondary
    End point timeframe
    At Month 2
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    184
    165
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        mIU/mL
    15795.5 (11603.3 to 21502.2)
    791.6 (648.9 to 965.5)
    No statistical analyses for this end point

    Secondary: Anti-gE antibody concentrations

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    End point title
    		 Anti-gE antibody concentrations
    End point description
    Antibody concentrations were determined by ELISA, presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). This parameter was assessed in all vaccinated subjects.
    End point type
    Secondary
    End point timeframe
    At Months 0, 1, 2 and 13
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    217
    198
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Anti-gE, Month 0
    964.0 (814.5 to 1140.8)
    883.7 (749.9 to 1041.4)
        Anti-gE, Month 1
    4216.5 (3328.6 to 5341.4)
    824.2 (699.4 to 971.3)
        Anti-gE, Month 2
    13445.6 (10158.9 to 17795.6)
    832.0 (701.1 to 987.3)
        Anti-gE, Month 13
    5202.7 (4074.8 to 6642.8)
    895.4 (734.5 to 1091.5)
    No statistical analyses for this end point

    Secondary: Vaccine response rate (VRR) for anti-gE antibody concentrations

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    End point title
    		 Vaccine response rate (VRR) for anti-gE antibody concentrations
    End point description
    Vaccine response rate refers to the percentage of subjects with a vaccine response, as determined by ELISA. Vaccine response was defined as: For initially seronegative subjects, antibody concentration at Month 2 ≥ 4 fold the cut-off for anti-gE (4x97 mIU/mL). For initially seropositive subjects, antibody concentration at Month 2 ≥ 4 fold the pre -vaccination antibody concentration. Vaccine response was measured in all subjects.
    End point type
    Secondary
    End point timeframe
    At Months 1, 2 and 13
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    217
    198
    Units: Percentage
    number (confidence interval 95%)
        VRR, anti-gE, Month 1
    44.2 (37.4 to 51.1)
    0.0 (0.0 to 1.9)
        VRR, anti-gE, Month 2
    65.4 (58.7 to 71.7)
    0.5 (0.0 to 2.8)
        VRR, anti-gE, Month 13
    52.1 (44.2 to 59.9)
    3.6 (1.2 to 8.1)
    No statistical analyses for this end point

    Secondary: Frequency of gE -specific cluster of differentiation 4 (CD4) [2+] T-cells expressing at least 2 activation markers

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    End point title
    		 Frequency of gE -specific cluster of differentiation 4 (CD4) [2+] T-cells expressing at least 2 activation markers
    End point description
    Among markers expressed were interferon-gamma (IFN-γ), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α) and cluster of differentiation 40 ligand (CD40L), as determined by in vitro intracellular cytokine staining (ICS).
    End point type
    Secondary
    End point timeframe
    At Months 0, 1, 2 and 13
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    58
    51
    Units: CD4 [2+] T-cells/million T-cells
    arithmetic mean (standard deviation)
        CD4 [2+], Month 0
    226.78 ( 659.84 )
    147.30 ( 191.91 )
        CD4 [2+], Month 1
    1261.67 ( 2318.36 )
    196.74 ( 332.52 )
        CD4 [2+], Month 2
    6083.98 ( 10467.57 )
    318.20 ( 1000.90 )
        CD4 [2+], Month 13
    3626.87 ( 7758.18 )
    181.23 ( 387.90 )
    No statistical analyses for this end point

    Secondary: Vaccine response rates (VRR) for gE-specific CD4 [2+] T-cells, expressing at least 2 activation markers

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    End point title
    		 Vaccine response rates (VRR) for gE-specific CD4 [2+] T-cells, expressing at least 2 activation markers
    End point description
    Among markers expressed were IFN-γ, IL-2, TNF-α and CD40L, as determined by in vitro ICS. Vaccine response was defined as: For initially subjects with pre-vaccination T-cell frequencies below the threshold, at least a 2-fold increase as compared to the threshold (2x<320> Events/106 CD4+ T cells). For initially subjects with pre-vaccination T-cell frequencies above the threshold, at least a 2-fold increase as compared to pre-vaccination T-cell frequencies.
    End point type
    Secondary
    End point timeframe
    At Months 1, 2 and 13
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    48
    47
    Units: Percentage
    number (confidence interval 95%)
        CD4 [2+], Month 1
    37.5 (24.0 to 52.6)
    2.1 (0.1 to 11.3)
        CD4 [2+], Month 2
    83.7 (69.3 to 93.2)
    6.8 (1.4 to 18.7)
        CD4 [2+], Month 13
    66.7 (48.2 to 82.0)
    6.5 (0.8 to 21.4)
    No statistical analyses for this end point

    Secondary: Number of subjects with serious adverse events (SAEs)

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    End point title
    		 Number of subjects with serious adverse events (SAEs)
    End point description
    A Serious adverse event (SAE) is any untoward medical occurrence that result in death, is life threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject. Related = SAEs assessed by the investigator as causally related to the study vaccination
    End point type
    Secondary
    End point timeframe
    From first vaccination at Month 0 up to study end at Month 13
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    283
    279
    Units: Participants
        At least one SAE, up to Month 6
    50
    60
        Related SAEs, up to Month 6
    0
    1
        At least one SAE, up to Month 13
    66
    82
        Related SAEs, up to Month 13
    1
    1
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any potential immune-mediated diseases (pIMDs)

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    End point title
    		 Number of subjects reporting any potential immune-mediated diseases (pIMDs)
    End point description
    Potential immune-mediated diseases (pIMDs) 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
    End point type
    Secondary
    End point timeframe
    From first vaccination at Month 0 up to study end at Month 13
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    283
    279
    Units: Participants
        Up to Month 6
    3
    1
        Up to Month 13
    3
    2
    No statistical analyses for this end point

    Secondary: Time to occurrence of any confirmed HZ case

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    End point title
    		 Time to occurrence of any confirmed HZ case
    End point description
    Time to occurrence of any confirmed HZ case is expressed in terms of incidence rate of subjects with at least one event. Hence, person-year rate = number of episodes (n)/ sum of follow-up period (censored at the first occurrence of an event) expressed in years (T[year)]). Follow-up period starts Day 1 of vaccination. Any clinically suspected case of HZ (defined as (1) a new rash characteristic of HZ (e.g., unilateral, dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or other sensations), or a vesicular rash suggestive of Varicella Zoster Virus (VZV) infection regardless of the distribution, and no alternative diagnosis; or (2) a clinical presentation (symptoms and/or signs) and specific laboratory findings suggestive of VZV infection in the absence of characteristic HZ or VZV rash.) The endpoint is confirmed in two ways: (1) By Polymerase Chain Reaction (PCR) or (2) By the HZ Ascertainment Committee. The PCR is used as primary classification method.
    End point type
    Secondary
    End point timeframe
    From Month 0 until study end (Month 13)
    End point values
    		 GSK1437173A Group Placebo Group
    Number of subjects analysed
    283
    279
    Units: Person-Year rate
        number (confidence interval 95%)
    0.02 (0.009 to 0.045)
    0.071 (0.045 to 0.111)
    No statistical analyses for this end point

    Secondary: Geometric mean concentrations (GMCs) of anti-gE antibodies

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    End point title
    		 Geometric mean concentrations (GMCs) of anti-gE antibodies
    End point description
    GMCs of anti-gE antibodies were tabulated per study group and HZ confirmed/non-confirmed status and expressed in milli-international units per milliliter (mIU/mL).
    End point type
    Secondary
    End point timeframe
    At Months 0 and 2
    End point values
    		 GSK1437173A HZ cases Sub-Group GSK1437173A Non-HZ cases Sub-Group Placebo HZ cases Sub-Group Placebo Non-HZ cases Sub-Group
    Number of subjects analysed
    2
    257
    12
    240
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        PRE (N=2,257,12,240)
    115.9 (0 to 7406196)
    973.6 (835.6 to 1134.4)
    984.5 (500.7 to 1935.7)
    866.3 (745.5 to 1006.6)
        Month 2 (N=2, 253, 12, 234)
    184.0 (0 to 4187800000)
    12517.4 (9662.0 to 16216.6)
    960.5 (454.2 to 2031.1)
    802.9 (686.7 to 938.9)
    No statistical analyses for this end point

    Secondary: Mean Geometric Increase (MGI) of anti-gE antibody ELISA concentrations

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    End point title
    		 Mean Geometric Increase (MGI) of anti-gE antibody ELISA concentrations
    End point description
    MGI was tabulated per study group and HZ confirmed/non-confirmed status. MGI was defined as the Geometric mean of the within subject ratios of the post-vaccination reciprocal anti-gE concentration to the Month 0 reciprocal anti-gE concentration.
    End point type
    Secondary
    End point timeframe
    At Month 2
    End point values
    		 GSK1437173A HZ cases Sub-Group GSK1437173A Non-HZ cases Sub-Group Placebo HZ cases Sub-Group Placebo Non-HZ cases Sub-Group
    Number of subjects analysed
    2
    253
    12
    233
    Units: Fold Increase
        log mean (confidence interval 95%)
    1.59 (0.00 to 565.45)
    13.07 (9.93 to 17.22)
    0.98 (0.80 to 1.19)
    0.94 (0.88 to 1.00)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited and unsolicited symptoms: within the 30-day (Days 0-29) post-vaccination period; SAEs: up to study end, at Month 13.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Placebo Group
    Reporting group description
    		 Subjects who received placebo doses according to a 0, 1 Months schedule (The second dose of placebo could be administered 1 - 2 months after the first dose).

    Reporting group title
    GSK1437173A Group
    Reporting group description
    		 Subjects who received GSK1437173A vaccine according to a 0, 1 Months schedule (The second dose of study vaccine could be administered 1 - 2 months after the first dose).

    Serious adverse events
    		 Placebo Group GSK1437173A Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    82 / 279 (29.39%)
    66 / 283 (23.32%)
         number of deaths (all causes)
    37
    29
         number of deaths resulting from adverse events
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia
         subjects affected / exposed
    1 / 279 (0.36%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Acute myeloid leukaemia
         subjects affected / exposed
    8 / 279 (2.87%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 3
         deaths causally related to treatment / all
    0 / 7
    0 / 2
    Anaplastic large-cell lymphoma
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blastic plasmacytoid dendritic cell neoplasia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Brain neoplasm
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cervix cancer metastatic
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    2 / 279 (0.72%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Haemangioma
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    1 / 279 (0.36%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    Leukaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant melanoma
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Metastases to peritoneum
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myelodysplastic syndrome
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Myeloid leukaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-hodgkin's lymphoma
         subjects affected / exposed
    2 / 279 (0.72%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Plasma cell leukaemia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    6 / 279 (2.15%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 2
         deaths causally related to treatment / all
    0 / 5
    0 / 2
    Post transplant lymphoproliferative disorder
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Precursor t-lymphoblastic lymphoma/leukaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    T-cell lymphoma
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    T-cell type acute leukaemia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Embolism
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Surgical and medical procedures
    Finger amputation
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stem cell transplant
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adhesion
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    2 / 279 (0.72%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death neonatal
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    General physical health deterioration
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nodule
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 279 (1.08%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Immune system disorders
    Acute graft versus host disease in skin
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic shock
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Graft versus host disease
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft versus host disease in liver
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cyst ruptured
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (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
    Acute respiratory failure
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dyspnoea
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 279 (0.72%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    Rhinorrhoea
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Disorientation
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foreign body in gastrointestinal tract
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (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
    2 / 279 (0.72%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple fractures
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure
         subjects affected / exposed
    0 / 279 (0.00%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiovascular disorder
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Dysarthria
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Guillain-barre syndrome
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemorrhagic transformation stroke
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Loss of consciousness
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parkinsonism
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coagulopathy
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytopenia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Febrile neutropenia
         subjects affected / exposed
    11 / 279 (3.94%)
    14 / 283 (4.95%)
         occurrences causally related to treatment / all
    0 / 16
    0 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 279 (0.72%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pancytopenia
         subjects affected / exposed
    2 / 279 (0.72%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 279 (0.36%)
    4 / 283 (1.41%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Ear and labyrinth disorders
    Deafness neurosensory
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ophthalmoplegia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anal fistula
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    2 / 279 (0.72%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hepatitis fulminant
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erythema nodosum
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (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
    Acute kidney injury
         subjects affected / exposed
    4 / 279 (1.43%)
    5 / 283 (1.77%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Hydronephrosis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fasciitis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc disorder
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Aspergillus infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 279 (0.36%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    0 / 279 (0.00%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Campylobacter colitis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corynebacterium bacteraemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 279 (0.00%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ecthyma
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epiglottitis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fungal infection
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis b
         subjects affected / exposed
    0 / 279 (0.00%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Herpes zoster
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Infection
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 279 (0.72%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis cryptococcal
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis externa
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perichondritis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    11 / 279 (3.94%)
    11 / 283 (3.89%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 12
         deaths causally related to treatment / all
    0 / 5
    0 / 4
    Pneumonia cytomegaloviral
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia klebsiella
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 279 (0.36%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary mycosis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyomyositis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    2 / 279 (0.72%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    6 / 279 (2.15%)
    5 / 283 (1.77%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 5
         deaths causally related to treatment / all
    0 / 5
    0 / 1
    Septic shock
         subjects affected / exposed
    3 / 279 (1.08%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 3
    Sinusitis
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 279 (0.36%)
    3 / 283 (1.06%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Staphylococcal infection
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal bacteraemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Subcutaneous abscess
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic candida
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth abscess
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 279 (0.00%)
    2 / 283 (0.71%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Varicella zoster virus infection
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (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
    Diabetes mellitus
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fluid retention
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 279 (0.00%)
    1 / 283 (0.35%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 279 (0.36%)
    0 / 283 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Group GSK1437173A Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    146 / 279 (52.33%)
    252 / 283 (89.05%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    65 / 279 (23.30%)
    115 / 283 (40.64%)
         occurrences all number
    86
    166
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    19 / 279 (6.81%)
    69 / 283 (24.38%)
         occurrences all number
    24
    89
    Fatigue
         subjects affected / exposed
    102 / 279 (36.56%)
    163 / 283 (57.60%)
         occurrences all number
    140
    250
    Pain
         subjects affected / exposed
    46 / 279 (16.49%)
    221 / 283 (78.09%)
         occurrences all number
    60
    372
    Pyrexia
         subjects affected / exposed
    24 / 279 (8.60%)
    74 / 283 (26.15%)
         occurrences all number
    30
    96
    Swelling
         subjects affected / exposed
    2 / 279 (0.72%)
    63 / 283 (22.26%)
         occurrences all number
    3
    89
    Gastrointestinal disorders
    Gastrointestinal disorder
         subjects affected / exposed
    29 / 279 (10.39%)
    76 / 283 (26.86%)
         occurrences all number
    40
    101
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    6 / 279 (2.15%)
    116 / 283 (40.99%)
         occurrences all number
    7
    165
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    48 / 279 (17.20%)
    123 / 283 (43.46%)
         occurrences all number
    60
    175

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Feb 2013
    • Section 7.5 has been amended to indicate that the second vaccination is contraindicated in subjects who experience a pIMD between dose 1 and dose 2 of study vaccine or placebo. This amendment is being implemented to fulfil a request of the Swedish Medical Products Agency (MPA). The amendment is not in response to any safety concern arising from an event or series of events in any completed or ongoing clinical studies that have been or are being conducted as part of GSK’s Zoster vaccine program or in studies conducted as part of other GSK vaccine programs. • Also in response to Sweden’s MPA request, text has been added to Section 8.1.5.1 to clarify how pIMDs are handled by GSK Biologicals when reported by the investigator. • Two sentences were added to Section 7.6.1 (Recording of concomitant medications/products and concomitant vaccination) for clarification:  Any concomitant vaccination administered in the period starting 30 days before the first dose of study vaccine and ending within 30 days post last dose.  Any concomitant medications/products/vaccines listed in Section 7.6.2 • Minor typographical and document formatting errors throughout the protocol have been corrected.
    14 Jul 2014
    • For clarification, it has been detailed in the glossary of terms that cancer therapy, as included in the inclusion criteria in this protocol, pertains to treatments that may put the subject at an increased risk for HZ and it comprises direct anti-cancer treatments (chemotherapy and/or immunotherapy; if radiotherapy it must be in combination with either chemotherapy or immunotherapy) that are immunosuppressive, and immunosuppressive therapies administered as part of the anti-cancer treatment or to avoid/treat complications of the anti-cancer treatment. • To address a request from the Food and Drug Administration (FDA), the objective to evaluate anti-gE humoral immune responses at Month 2 following a two-dose administration of the HZ/su vaccine, as compared to placebo, in subjects with haematologic malignancies excluding subjects with Non-Hodgkin B-cell Lymphoma and Chronic Lymphocytic Leukaemia, has been promoted from secondary to primary confirmatory objective. • The cut-off of the gE-specific ELISA assay has been changed from 18 to 97 mIU/mL. Background signal has been measured with the anti-gE ELISA on samples from Varicella Zoster Virus (VZV) naïve paediatric subjects. • The list of potential immune-mediated diseases has been updated.

    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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