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    Clinical Trial Results:
    A Randomized, Double-blind, Phase 3 Efficacy Trial of PROSTVAC-V/F ± GM-CSF in Men With Asymptomatic or Minimally Symptomatic Metastatic, Castrate-Resistant Prostate Cancer

    Summary
    EudraCT number
    2010-021196-85
    Trial protocol
    GB   ES   BE   EE   IS   DE   DK   NL   PL  
    Global end of trial date
    02 Oct 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    04 Jan 2019
    First version publication date
    04 Jan 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    BNIT-PRV-301
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01322490
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Bavarian Nordic, Inc.
    Sponsor organisation address
    3025 Carrington Mill Blvd, Suite 100, Morrisville, NC, United States, 27560
    Public contact
    Cesar Pico-Navarro, Bavarian Nordic, Inc., +34 628 748 006, Cesar.Pico-Navarro@bavarian-nordic.com
    Scientific contact
    Cesar Pico-Navarro, Bavarian Nordic, Inc., +34 628 748 006, Cesar.Pico-Navarro@bavarian-nordic.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
    02 Oct 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 Jun 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Oct 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To ascertain whether the survival of subjects randomized to Arm V+G (PROSTVAC-V/F plus GM-CSF) or to Arm V (PROSTVAC-V/F) is superior to that from subjects randomized to Arm P (placebo control).
    Protection of trial subjects
    The investigator ensured that this clinical trial was conducted in complete accordance with the provisions of the Declaration of Helsinki (1996), the national laws and other guidelines for the conduct of clinical trials, like the ICH Harmonized Tripartite Guideline for Good Clinical Practice (GCP), to guarantee the greatest subject protection possible. Subjects had to be informed unequivocally that they were able to refuse participation in the trial, that they were able to withdraw from the trial at any time and for whatever reason, and that withdrawal of consent did not affect their subsequent medical treatment or relationship with the treating physician.
    Background therapy
    -
    Evidence for comparator
    The trial was designed to evaluate overall survival (OS) in two separate comparisons: PROSTVAC + GM-CSF versus control, and PROSTVAC without GM-CSF versus control.
    Actual start date of recruitment
    28 Nov 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    27 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 101
    Country: Number of subjects enrolled
    Canada: 69
    Country: Number of subjects enrolled
    Israel: 29
    Country: Number of subjects enrolled
    Puerto Rico: 5
    Country: Number of subjects enrolled
    Russian Federation: 163
    Country: Number of subjects enrolled
    United States: 394
    Country: Number of subjects enrolled
    Netherlands: 16
    Country: Number of subjects enrolled
    Poland: 20
    Country: Number of subjects enrolled
    Spain: 126
    Country: Number of subjects enrolled
    United Kingdom: 99
    Country: Number of subjects enrolled
    Belgium: 30
    Country: Number of subjects enrolled
    Denmark: 108
    Country: Number of subjects enrolled
    Estonia: 20
    Country: Number of subjects enrolled
    France: 85
    Country: Number of subjects enrolled
    Germany: 22
    Country: Number of subjects enrolled
    Iceland: 10
    Worldwide total number of subjects
    1297
    EEA total number of subjects
    536
    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)
    272
    From 65 to 84 years
    965
    85 years and over
    60

    Subject disposition

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    Recruitment
    Recruitment details
    The study population for the trial was intended to approximate the population enrolled in the randomized phase 2 trial in which an overall survival advantage was observed. Clinical trial data supported the hypothesis that patients with less aggressive and lower burden disease were more likely to benefit from therapeutic cancer vaccines.

    Pre-assignment
    Screening details
    Screening activities were completed within 28 days prior to the first dose of any study medication - between days -28 and -1 (Week -4 to Week 0), and were completed prior to dosing.

    Period 1
    Period 1 title
    Treatment Phase
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    The trial was conducted in a double-blind manner. Subjects and investigators were blinded as to their specific treatment assignment. The sponsor controlled and documented any disclosure of treatment assignments. These procedures ensured that neither the sponsor’s monitoring staff nor the investigator nor other site staff had premature access to individual subject treatment assignment.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Arm VG (PROSTVAC + GM-CSF)
    Arm description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a SC GM-CSF on the day of immunization and for the subsequent three days (SC GM-CSF injection within 5 mm of the original PROSTVAC injection site).
    Arm type
    Experimental

    Investigational medicinal product name
    PROSTVAC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PROSTVAC-V for SC injection was 0.5 mL and contained at least 2 x 108 Inf.U PROSTVAC-V. PROSTVAC-F for SC injection was 0.5 mL and contained at least 1 x 109 Inf.U PROSTVAC-F.

    Investigational medicinal product name
    GM-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GM-CSF (sargramostim; Leukine®: 250 μg, lyophilized) is a glycosylated, recombinant human GM-CSF. Lyophilized GM-CSF was reconstituted using 1.0 mL of room-temperature bacteriostatic water for injection (USP-grade or equivalent). Each 100 μg doses of GM-CSF was drawn into labeled syringes by an independent, unblinded research pharmacist or designee for use by the clinic staff or for use by individual subjects for home injection.

    Arm title
    Arm V (PROSTVAC + GM-CSF placebo)
    Arm description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a GM-CSF placebo on the day of immunization and for the subsequent three days.
    Arm type
    Experimental

    Investigational medicinal product name
    PROSTVAC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PROSTVAC-V for SC injection was 0.5 mL and contained at least 2 x 108 Inf.U PROSTVAC-V. PROSTVAC-F for SC injection was 0.5 mL and contained at least 1 x 109 Inf.U PROSTVAC-F.

    Investigational medicinal product name
    GM-CSF placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GM-CSF placebo was USP-grade or equivalent bacteriostatic sodium chloride (saline) for injection.

    Arm title
    Arm P (Vaccine placebo + GM-CSF placebo)
    Arm description
    The trial treatment consisted of a single Vaccine placebo injection on Day 1 (Week 1), followed by six GM-CSF placebo injections: one injection administered at each of Weeks 3, 5, 9, 13, 17, and 21. Each Vaccine placebo injection was accompanied by administration of an GM-CSF placebo injection on the day of immunization and for three subsequent days (placebo SC injection within 5 mm of the original placebo injection site).
    Arm type
    Placebo

    Investigational medicinal product name
    Vaccine placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Vaccine placebo is empty fowlpox vector matching PROSTVAC.

    Investigational medicinal product name
    GM-CSF placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GM-CSF placebo was USP-grade or equivalent bacteriostatic sodium chloride (saline) for injection.

    Number of subjects in period 1
    Arm VG (PROSTVAC + GM-CSF) Arm V (PROSTVAC + GM-CSF placebo) Arm P (Vaccine placebo + GM-CSF placebo)
    Started
    432
    432
    433
    Completed
    279
    300
    280
    Not completed
    153
    132
    153
         Randomized but not treated
    3
    3
    5
         Protocol deviation
    5
    7
    4
         Other
    2
    2
    1
         Physician decision
    2
    -
    1
         Non-Compliance
    -
    -
    1
         Adverse event, serious fatal
    7
    5
    3
         Adverse event, non-fatal
    18
    12
    15
         Progressive Disease
    100
    89
    112
         Consent withdrawn by subject
    16
    14
    11
    Period 2
    Period 2 title
    Long-term Follow-up (LTFU)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Arm VG (PROSTVAC + GM-CSF)
    Arm description
    Following the completion of the treatment phase, all subjects from Arm VG (PROSTVAC + GM-CSF) automatically entered the LTFU Phase, during which trial visits occurred every 6 months and subjects received standard-of-care treatment as determined by the investigator or treating physician. All subjects are followed for 12 months after the required number of 534 events for each between-arm comparison was reached. Concomitant medications, subject health status, disease status, newly diagnosed autoimmune diseases, and subsequent prostate cancer therapies were collected at each six-month LTFU visit.
    Arm type
    Experimental

    Investigational medicinal product name
    PROSTVAC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PROSTVAC-V for SC injection was 0.5 mL and contained at least 2 x 108 Inf.U PROSTVAC-V. PROSTVAC-F for SC injection was 0.5 mL and contained at least 1 x 109 Inf.U PROSTVAC-F.

    Investigational medicinal product name
    GM-CSF
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GM-CSF (sargramostim; Leukine®: 250 μg, lyophilized) is a glycosylated, recombinant human GM-CSF. Lyophilized GM-CSF was reconstituted using 1.0 mL of room-temperature bacteriostatic water for injection (USP-grade or equivalent). Each 100 μg doses of GM-CSF was drawn into labeled syringes by an independent, unblinded research pharmacist or designee for use by the clinic staff or for use by individual subjects for home injection.

    Arm title
    Arm V (PROSTVAC + GM-CSF placebo)
    Arm description
    Following the completion of the treatment phase, all subjects from Arm V (PROSTVAC + GM-CSF placebo) automatically entered the LTFU Phase, during which trial visits occurred every 6 months and subjects received standard-of-care treatment as determined by the investigator or treating physician. All subjects are followed for 12 months after the required number of 534 events for each between-arm comparison was reached. Concomitant medications, subject health status, disease status, newly diagnosed autoimmune diseases, and subsequent prostate cancer therapies were collected at each six-month LTFU visit.
    Arm type
    Experimental

    Investigational medicinal product name
    PROSTVAC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    PROSTVAC-V for SC injection was 0.5 mL and contained at least 2 x 108 Inf.U PROSTVAC-V. PROSTVAC-F for SC injection was 0.5 mL and contained at least 1 x 109 Inf.U PROSTVAC-F.

    Investigational medicinal product name
    GM-CSF placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GM-CSF placebo was USP-grade or equivalent bacteriostatic sodium chloride (saline) for injection.

    Arm title
    Arm P (Vaccine placebo + GM-CSF placebo)
    Arm description
    Following the completion of the treatment phase, all subjects from Arm P (Vaccine placebo + GM-CSF placebo) automatically entered the LTFU Phase, during which trial visits occurred every 6 months and subjects received standard-of-care treatment as determined by the investigator or treating physician. All subjects are followed for 12 months after the required number of 534 events for each between-arm comparison was reached. Concomitant medications, subject health status, disease status, newly diagnosed autoimmune diseases, and subsequent prostate cancer therapies were collected at each six-month LTFU visit.
    Arm type
    Placebo

    Investigational medicinal product name
    Vaccine placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Vaccine placebo is empty fowlpox vector matching PROSTVAC.

    Investigational medicinal product name
    GM-CSF placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    GM-CSF placebo was USP-grade or equivalent bacteriostatic sodium chloride (saline) for injection.

    Number of subjects in period 2
    Arm VG (PROSTVAC + GM-CSF) Arm V (PROSTVAC + GM-CSF placebo) Arm P (Vaccine placebo + GM-CSF placebo)
    Started
    279
    300
    280
    Completed
    0
    0
    0
    Not completed
    408
    409
    413
         Study Terminated by Sponsor
    158
    160
    165
         Death
    239
    235
    236
         Missing
    1
    -
    1
         Other
    2
    3
    2
         Consent withdrawn by subject
    6
    9
    6
         Lost to follow-up
    2
    2
    3
    Joined
    129
    109
    133
         Subjects Agreed to Continue into LTFU Phase
    129
    109
    133

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm VG (PROSTVAC + GM-CSF)
    Reporting group description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a SC GM-CSF on the day of immunization and for the subsequent three days (SC GM-CSF injection within 5 mm of the original PROSTVAC injection site).

    Reporting group title
    Arm V (PROSTVAC + GM-CSF placebo)
    Reporting group description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a GM-CSF placebo on the day of immunization and for the subsequent three days.

    Reporting group title
    Arm P (Vaccine placebo + GM-CSF placebo)
    Reporting group description
    The trial treatment consisted of a single Vaccine placebo injection on Day 1 (Week 1), followed by six GM-CSF placebo injections: one injection administered at each of Weeks 3, 5, 9, 13, 17, and 21. Each Vaccine placebo injection was accompanied by administration of an GM-CSF placebo injection on the day of immunization and for three subsequent days (placebo SC injection within 5 mm of the original placebo injection site).

    Reporting group values
    Arm VG (PROSTVAC + GM-CSF) Arm V (PROSTVAC + GM-CSF placebo) Arm P (Vaccine placebo + GM-CSF placebo) Total
    Number of subjects
    432 432 433 1297
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    93 88 91 272
        From 65-84 years
    322 325 318 965
        85 years and over
    17 19 24 60
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    70.6 (45 to 90) 71.3 (49 to 90) 71.3 (46 to 93) -
    Gender categorical
    Units: Subjects
        Female
    0 0 0 0
        Male
    432 432 433 1297
    Subject analysis sets

    Subject analysis set title
    Intent-to-Treat Set (ITT set)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Intent-to-Treat Set (ITT Set) included all subjects who were randomized.

    Subject analysis set title
    FAS (Full Analysis Set)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Full Analysis Set (FAS) included all subjects who initiated trial treatment.

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Safety Analysis Set included all subjects who initiated trial treatment.

    Subject analysis sets values
    Intent-to-Treat Set (ITT set) FAS (Full Analysis Set) Safety Analysis Set
    Number of subjects
    1297
    1286
    1286
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    272
    271
    271
        From 65-84 years
    965
    956
    956
        85 years and over
    60
    59
    59
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    71.1 (45 to 93)
    71.1 (45 to 93)
    71.1 (45 to 93)
    Gender categorical
    Units: Subjects
        Female
    0
    0
    0
        Male
    1297
    1286
    1286

    End points

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    End points reporting groups
    Reporting group title
    Arm VG (PROSTVAC + GM-CSF)
    Reporting group description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a SC GM-CSF on the day of immunization and for the subsequent three days (SC GM-CSF injection within 5 mm of the original PROSTVAC injection site).

    Reporting group title
    Arm V (PROSTVAC + GM-CSF placebo)
    Reporting group description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a GM-CSF placebo on the day of immunization and for the subsequent three days.

    Reporting group title
    Arm P (Vaccine placebo + GM-CSF placebo)
    Reporting group description
    The trial treatment consisted of a single Vaccine placebo injection on Day 1 (Week 1), followed by six GM-CSF placebo injections: one injection administered at each of Weeks 3, 5, 9, 13, 17, and 21. Each Vaccine placebo injection was accompanied by administration of an GM-CSF placebo injection on the day of immunization and for three subsequent days (placebo SC injection within 5 mm of the original placebo injection site).
    Reporting group title
    Arm VG (PROSTVAC + GM-CSF)
    Reporting group description
    Following the completion of the treatment phase, all subjects from Arm VG (PROSTVAC + GM-CSF) automatically entered the LTFU Phase, during which trial visits occurred every 6 months and subjects received standard-of-care treatment as determined by the investigator or treating physician. All subjects are followed for 12 months after the required number of 534 events for each between-arm comparison was reached. Concomitant medications, subject health status, disease status, newly diagnosed autoimmune diseases, and subsequent prostate cancer therapies were collected at each six-month LTFU visit.

    Reporting group title
    Arm V (PROSTVAC + GM-CSF placebo)
    Reporting group description
    Following the completion of the treatment phase, all subjects from Arm V (PROSTVAC + GM-CSF placebo) automatically entered the LTFU Phase, during which trial visits occurred every 6 months and subjects received standard-of-care treatment as determined by the investigator or treating physician. All subjects are followed for 12 months after the required number of 534 events for each between-arm comparison was reached. Concomitant medications, subject health status, disease status, newly diagnosed autoimmune diseases, and subsequent prostate cancer therapies were collected at each six-month LTFU visit.

    Reporting group title
    Arm P (Vaccine placebo + GM-CSF placebo)
    Reporting group description
    Following the completion of the treatment phase, all subjects from Arm P (Vaccine placebo + GM-CSF placebo) automatically entered the LTFU Phase, during which trial visits occurred every 6 months and subjects received standard-of-care treatment as determined by the investigator or treating physician. All subjects are followed for 12 months after the required number of 534 events for each between-arm comparison was reached. Concomitant medications, subject health status, disease status, newly diagnosed autoimmune diseases, and subsequent prostate cancer therapies were collected at each six-month LTFU visit.

    Subject analysis set title
    Intent-to-Treat Set (ITT set)
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Intent-to-Treat Set (ITT Set) included all subjects who were randomized.

    Subject analysis set title
    FAS (Full Analysis Set)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Full Analysis Set (FAS) included all subjects who initiated trial treatment.

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Safety Analysis Set included all subjects who initiated trial treatment.

    Primary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    The primacy efficacy endpoint for the trial was OS. The survival analysis objective was to ascertain whether the survival-time distribution for subjects randomized to the investigational arm was consistent with longer survival compared to subjects randomized to the control arm. Two main overall comparisons of survival time were planned: a comparison between Arm VG and Arm P, and a comparison between Arm V and Arm P.
    End point type
    Primary
    End point timeframe
    Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause.
    End point values
    Arm VG (PROSTVAC + GM-CSF) Arm V (PROSTVAC + GM-CSF placebo) Arm P (Vaccine placebo + GM-CSF placebo)
    Number of subjects analysed
    432
    432
    433
    Units: Months
    median (confidence interval 95%)
        Overall Survival (months)
    33.2 (30.6 to 37.4)
    34.4 (31 to 36.9)
    34.3 (30.7 to 37.0)
    Statistical analysis title
    Statistical Analysis Plan (SAP) - Arm VG v. Arm P
    Comparison groups
    Arm P (Vaccine placebo + GM-CSF placebo) v Arm VG (PROSTVAC + GM-CSF)
    Number of subjects included in analysis
    865
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.5885
    Method
    Logrank
    Confidence interval
    Notes
    [1] - Overall survival is calculated as the date of (death/censoring - date of randomization + 1)/30.4375. Subjects who did not die are censored at last known alive date or datacut off date, whichever comes first. Quartiles and 95% CI are estimated using Kaplan-Meier methods. The 95% confidence intervals for the median OS times was calculated using the method by Brookmeyer and Crowley.
    Statistical analysis title
    Statistical Analysis Plan (SAP) - Arm V v. Arm P
    Comparison groups
    Arm V (PROSTVAC + GM-CSF placebo) v Arm P (Vaccine placebo + GM-CSF placebo)
    Number of subjects included in analysis
    865
    Analysis specification
    Pre-specified
    Analysis type
    superiority [2]
    P-value
    = 0.4742
    Method
    Logrank
    Confidence interval
    Notes
    [2] - Overall survival is calculated as the date of (death/censoring - date of randomization + 1)/30.4375. Subjects who did not die are censored at last known alive date or datacut off date, whichever comes first. Quartiles and 95% CI are estimated using Kaplan-Meier methods. The 95% confidence intervals for the median OS times was calculated using the method by Brookmeyer and Crowley.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The collection of AEs occurred from the signing of informed consent to 28 days following the administration of the last dose of study medication, which was approximately the Week 25/End of Treatment Visit for subjects who completed the treatment period.
    Adverse event reporting additional description
    Serious Adverse Events (SAEs) if ongoing at the End of Treatment visit were followed to resolution or until the investigator assessed the subject as stable. SAEs that were reported after the end of the treatment period were collected only if they were assessed by the investigator as being possibly or definitely related to study treatment.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Arm VG (PROSTVAC + GM-CSF)
    Reporting group description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a SC GM-CSF on the day of immunization and for the subsequent three days (SC GM-CSF injection within 5 mm of the original PROSTVAC injection site).

    Reporting group title
    Arm V (PROSTVAC + GM-CSF placebo)
    Reporting group description
    The trial treatment consisted of a single SC injection of PROSTVAC-V on day 0 (Week 1), followed by six PROSTVAC-F injections: each administered at days 14 (Week 3), 28 (Week 5), 56 (Week 9), 84 (Week 13), 112 (Week 17), and 140 (Week 21). Each PROSTVAC injection was accompanied by a GM-CSF placebo on the day of immunization and for the subsequent three days.

    Reporting group title
    Arm P (Vaccine placebo + GM-CSF placebo)
    Reporting group description
    The trial treatment consisted of a single Vaccine placebo injection on Day 1 (Week 1), followed by six GM-CSF placebo injections: one injection administered at each of Weeks 3, 5, 9, 13, 17, and 21. Each Vaccine placebo injection was accompanied by administration of an GM-CSF placebo injection on the day of immunization and for three subsequent days (placebo SC injection within 5 mm of the original placebo injection site).

    Serious adverse events
    Arm VG (PROSTVAC + GM-CSF) Arm V (PROSTVAC + GM-CSF placebo) Arm P (Vaccine placebo + GM-CSF placebo)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    56 / 429 (13.05%)
    56 / 429 (13.05%)
    53 / 428 (12.38%)
         number of deaths (all causes)
    254
    251
    245
         number of deaths resulting from adverse events
    5
    5
    3
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lymphoedema
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular compression
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Carcinoma in situ of skin
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Metastases to central nervous system
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastatic pain
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine carcinoma of the skin
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    2 / 429 (0.47%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Delirium
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Brain herniation
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis radiation
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gun shot wound
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic haematoma
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radiation oesophagitis
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord injury
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sternal fracture
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to various agents
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular bypass dysfunction
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    3 / 428 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 429 (0.23%)
    2 / 429 (0.47%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchiectasis
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 429 (0.23%)
    5 / 429 (1.17%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemolytic uraemic syndrome
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Histiocytosis haematophagic
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Normochromic normocytic anaemia
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral haematoma
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Cerebrovascular accident
         subjects affected / exposed
    2 / 429 (0.47%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cervical cord compression
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 429 (0.47%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Nerve compression
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral motor neuropathy
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radiculopathy
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    4 / 429 (0.93%)
    1 / 429 (0.23%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal detachment
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia strangulated
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proctitis
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 429 (0.00%)
    2 / 429 (0.47%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    7 / 429 (1.63%)
    2 / 429 (0.47%)
    4 / 428 (0.93%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 429 (0.23%)
    5 / 429 (1.17%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive uropathy
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelocaliectasis
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 429 (0.00%)
    2 / 429 (0.47%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder haemorrhage
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    4 / 429 (0.93%)
    6 / 429 (1.40%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    2 / 429 (0.47%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cell death
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendiceal abscess
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Catheter site infection
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 429 (0.00%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Perinephric abscess
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 429 (0.47%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 429 (0.23%)
    1 / 429 (0.23%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord infection
         subjects affected / exposed
    2 / 429 (0.47%)
    0 / 429 (0.00%)
    0 / 428 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 429 (0.00%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 429 (0.70%)
    1 / 429 (0.23%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 429 (0.00%)
    2 / 429 (0.47%)
    2 / 428 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 429 (0.23%)
    0 / 429 (0.00%)
    1 / 428 (0.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Arm VG (PROSTVAC + GM-CSF) Arm V (PROSTVAC + GM-CSF placebo) Arm P (Vaccine placebo + GM-CSF placebo)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    395 / 429 (92.07%)
    386 / 429 (89.98%)
    385 / 428 (89.95%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    23 / 429 (5.36%)
    28 / 429 (6.53%)
    22 / 428 (5.14%)
         occurrences all number
    23
    28
    22
    Hot flush
         subjects affected / exposed
    20 / 429 (4.66%)
    23 / 429 (5.36%)
    12 / 428 (2.80%)
         occurrences all number
    20
    23
    12
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    20 / 429 (4.66%)
    25 / 429 (5.83%)
    15 / 428 (3.50%)
         occurrences all number
    20
    25
    15
    Nervous system disorders
    Headache
         subjects affected / exposed
    43 / 429 (10.02%)
    32 / 429 (7.46%)
    36 / 428 (8.41%)
         occurrences all number
    43
    32
    36
    Dizziness
         subjects affected / exposed
    17 / 429 (3.96%)
    18 / 429 (4.20%)
    22 / 428 (5.14%)
         occurrences all number
    17
    18
    22
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    258 / 429 (60.14%)
    202 / 429 (47.09%)
    203 / 428 (47.43%)
         occurrences all number
    258
    202
    203
    Injection site pain
         subjects affected / exposed
    131 / 429 (30.54%)
    111 / 429 (25.87%)
    122 / 428 (28.50%)
         occurrences all number
    131
    111
    122
    Fatigue
         subjects affected / exposed
    105 / 429 (24.48%)
    94 / 429 (21.91%)
    91 / 428 (21.26%)
         occurrences all number
    105
    94
    91
    Injection site pruritus
         subjects affected / exposed
    109 / 429 (25.41%)
    77 / 429 (17.95%)
    57 / 428 (13.32%)
         occurrences all number
    109
    77
    57
    Injection site swelling
         subjects affected / exposed
    101 / 429 (23.54%)
    73 / 429 (17.02%)
    69 / 428 (16.12%)
         occurrences all number
    101
    73
    69
    Pyrexia
         subjects affected / exposed
    91 / 429 (21.21%)
    38 / 429 (8.86%)
    53 / 428 (12.38%)
         occurrences all number
    91
    38
    53
    Injection site induration
         subjects affected / exposed
    67 / 429 (15.62%)
    47 / 429 (10.96%)
    60 / 428 (14.02%)
         occurrences all number
    67
    47
    60
    Influenza like illness
         subjects affected / exposed
    55 / 429 (12.82%)
    44 / 429 (10.26%)
    36 / 428 (8.41%)
         occurrences all number
    55
    44
    36
    Asthenia
         subjects affected / exposed
    37 / 429 (8.62%)
    32 / 429 (7.46%)
    49 / 428 (11.45%)
         occurrences all number
    37
    32
    49
    Chills
         subjects affected / exposed
    44 / 429 (10.26%)
    34 / 429 (7.93%)
    35 / 428 (8.18%)
         occurrences all number
    44
    34
    35
    Injection site oedema
         subjects affected / exposed
    24 / 429 (5.59%)
    22 / 429 (5.13%)
    20 / 428 (4.67%)
         occurrences all number
    24
    22
    20
    Injection site warmth
         subjects affected / exposed
    28 / 429 (6.53%)
    15 / 429 (3.50%)
    23 / 428 (5.37%)
         occurrences all number
    28
    15
    23
    Pain in extremity
         subjects affected / exposed
    28 / 429 (6.53%)
    28 / 429 (6.53%)
    23 / 428 (5.37%)
         occurrences all number
    28
    28
    23
    Oedema peripheral
         subjects affected / exposed
    24 / 429 (5.59%)
    21 / 429 (4.90%)
    12 / 428 (2.80%)
         occurrences all number
    24
    21
    12
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    51 / 429 (11.89%)
    51 / 429 (11.89%)
    38 / 428 (8.88%)
         occurrences all number
    51
    51
    38
    Constipation
         subjects affected / exposed
    26 / 429 (6.06%)
    39 / 429 (9.09%)
    29 / 428 (6.78%)
         occurrences all number
    26
    39
    29
    Diarrhoea
         subjects affected / exposed
    29 / 429 (6.76%)
    38 / 429 (8.86%)
    21 / 428 (4.91%)
         occurrences all number
    29
    38
    21
    Vomiting
         subjects affected / exposed
    21 / 429 (4.90%)
    22 / 429 (5.13%)
    17 / 428 (3.97%)
         occurrences all number
    21
    22
    17
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    18 / 429 (4.20%)
    21 / 429 (4.90%)
    22 / 428 (5.14%)
         occurrences all number
    18
    21
    22
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    50 / 429 (11.66%)
    49 / 429 (11.42%)
    55 / 428 (12.85%)
         occurrences all number
    50
    49
    55
    Back pain
         subjects affected / exposed
    43 / 429 (10.02%)
    62 / 429 (14.45%)
    49 / 428 (11.45%)
         occurrences all number
    43
    62
    49
    Myalgia
         subjects affected / exposed
    35 / 429 (8.16%)
    36 / 429 (8.39%)
    43 / 428 (10.05%)
         occurrences all number
    35
    36
    43
    Musculoskeletal pain
         subjects affected / exposed
    28 / 429 (6.53%)
    15 / 429 (3.50%)
    21 / 428 (4.91%)
         occurrences all number
    28
    15
    21
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    25 / 429 (5.83%)
    39 / 429 (9.09%)
    31 / 428 (7.24%)
         occurrences all number
    25
    39
    31
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    18 / 429 (4.20%)
    23 / 429 (5.36%)
    23 / 428 (5.37%)
         occurrences all number
    18
    23
    23

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 May 2011
    Amendment 1 (dated 02 May 2011) clarified the vaccine nomenclature for consistency with all publications and trial support documents (e.g., IB, Trial Instruction Manual, etc.); changed the definition of excluded/concomitant therapies to exclude the use of secondary hormonal therapies during the Treatment Phase of the trial, and allowed the use of denosumab; restated Inclusion Criterion #5 as Exclusion Criterion #5; specified exclusion of patients receiving an investigational agent within 60 days of the first planned dose of PROSTVAC; added definition of overdose; corrected dosing information for GM-CSF; and administrative changes.
    17 Jun 2011
    Amendment 2 (dated 17 June 2011) clarified the vaccine placebo nomenclature for consistency throughout the protocol; added a placebo rationale; added language to specify who can fill syringes with investigational drug product; added Exclusion Criterion #15 and changed Exclusion Criterion #16; clarified scheduled opioid narcotic relief as a trigger for subject removal from therapy or assessment; clarified that diluent for GM-CSF and GM-CSF placebo was bacteriostatic water for injection; added explanation that laboratory procedures not routinely covered by a site’s designated laboratory must be reviewed for approval by the sponsor; clarified use of a central radiological review; added language to explain use of biomarkers; clarified that peripheral blood RNA samples would be collected; and administrative changes.
    12 Sep 2011
    Amendment 3 (dated 12 September 2011) (first subject enrolled in Dec 2011) the GM-CSF reconstitution volume was changed to reflect the volumes suggested in the manufacturer’s package insert; changed the GM-CSF placebo from bacteriostatic water to bacteriostatic saline; inclusion/exclusion criteria were clarified to maintain consistency with other parts of the protocol and to correct incorrectly stated units; added language to define/clarify that QOL instruments were applied where available; clarified footnote for laboratory tests to state that both troponin tests were preferred, but if only one of the troponin tests could be run, that would be accepted; added the explicit requirement for virology testing; added a specific requirement for a medical history update for newly diagnosed autoimmune diseases during LTFU; updated background material to include newly approved therapies and literature references; and administrative changes.
    01 Feb 2012
    Amendment 4 (dated 01 February 2012) revised sponsor contact information; clarified excluded chronic corticosteroid therapy; clarified Inclusion Criterion #4; revised the handling of used trial drug vials and syringes; clarified injection site management; added the QEQ-5D-3L to the QOL instruments; added the FACT-P, BPI-SF, and EQ-5D-3L to the LTFU; added calcium to the chemistry assay; clarified the sample collection time for the immune monitoring samples; revised drug accountability and reconciliation for PROSTVAC and GM-CSF to be performed by an unblinded monitor; clarified that vial numbers were recorded for drug accountability for PROSTVAC and lot numbers for GM-CSF; clarified procedures for re-screening; clarified definition of an SAE; and administrative changes.
    30 May 2012
    Amendment 5 (dated 30 May 2012) made changes for clarity and consistency and updated language to reflect that currently used in the field; affirmed the sponsor’s commitment to compliance with ICH/ European Medicines Agency and applicable regulations; and administrative changes; updated synopsis to match protocol body; minor language revisions, updated language for consistency with IB, removed upper age limit for subjects; added language that subjects must have documented asymptomatic or minimally symptomatic mCRPC; removed language that was within the pharmacy manual and replaced with reference to the pharmacy manual; removed references to the digital; thermometer and subject diary; added section for emergency procedures; listed examples of concurrent immunotherapy and immunosuppressive therapy; moved immune monitoring assessments from screening to day 1; removed hematology and serum chemistry from LTFU; clarified that LTFU surveys would only be completed at the first LTFU visit; removed text pertaining to a local laboratory; more clearly defined AEs; added reference to pregnant partner and informed consent; made consistent with the current Management Plan for Potential Serious Vaccinia Reaction; added new section to provide greater detail regarding the key elements of ICH E2A; added new section to provide greater detail regarding documenting and reporting of AEs and SAEs in accordance with applicable global regulations; and administrative changes.
    20 Aug 2015
    Amendment 6 (dated 20 August 2015) included revision to the LTFU data collection process to increase subject retention; revision to biological and immune response assessments supporting exploratory endpoints; addition of language to clarify AE/SAE reporting requirements pertaining to progression of underlying malignancy; revised definition of analysis sets in Statistical Analysis section to align with SAP; incorporation of France- and Germany-specific protocol amendment language; and administrative changes.
    07 Feb 2017
    Amendment 7 (dated 07 February 2017) was an administrative amendment to address feedback from the Paul-Ehrlich-Institut (PEI) in Germany, who requested that the study protocol be updated to contain details regarding the Interim Analyses described in the Statistical Analysis Plan for this study. There is no impact to study design, conduct, or endpoints as a result of the language provided in protocol Section 9.8, Interim Analyses. In addition, the sponsor address and medical monitor have 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.
    The study has discontinued due to futility.
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