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    Clinical Trial Results:
    A Randomized Phase 3 Study of AM0010 in Combination with FOLFOX Compared with FOLFOX Alone as Second-line Therapy in Patients with Metastatic Pancreatic Cancer that has Progressed During or Following a First-Line Gemcitabine Containing Regimen

    Summary
    EudraCT number
    2016-003858-33
    Trial protocol
    AT   ES   DE   BE   GB   PL   FR   IT  
    Global end of trial date
    05 Mar 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    30 Aug 2020
    First version publication date
    30 Aug 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    J1L-AM-JZGB
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02923921
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Trial Number: 17158
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    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
    05 Mar 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Mar 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of pegilodecakin in combination with FOLFOX versus FOLFOX alone in participants with metastatic pancreatic cancer as measured by overall survival.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Mar 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Efficacy
    Long term follow-up duration
    36 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 73
    Country: Number of subjects enrolled
    Taiwan: 15
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    United States: 182
    Country: Number of subjects enrolled
    Australia: 30
    Country: Number of subjects enrolled
    Austria: 13
    Country: Number of subjects enrolled
    Belgium: 36
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Germany: 20
    Country: Number of subjects enrolled
    Italy: 67
    Country: Number of subjects enrolled
    Korea, Republic of: 89
    Country: Number of subjects enrolled
    Poland: 13
    Worldwide total number of subjects
    567
    EEA total number of subjects
    242
    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)
    278
    From 65 to 84 years
    286
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    No Text Available

    Pre-assignment
    Screening details
    In the Participant Flow, participants who completed were those who died due to any cause or were alive and on study at conclusion but off treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Pegilodecakin + FOLFOX
    Arm description
    Pegilodecakin 5 microgram per kilogram (μg/kg) dosed as one of the following 2 fixed doses: 0.4 milligram (mg) for participants weighing less than or equal to (≤) 80 kg or 0.8 mg for participants weighing greater than (>) 80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) plus FOLFOX [dl-Leucovorin (dl-LV) 400 milligram per meter square (mg/m2) and oxaliplatin 85 mg/m2 followed by bolus 5-fluorouracil (5-FU) 400 mg/m2 and a 46 to 48 hour infusion of 5- FU 2400 mg/m2] initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. After discontinuation of FOLFOX in the absence of tumor progression [that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing>80 kg.
    Arm type
    Experimental

    Investigational medicinal product name
    Pegilodecakin
    Investigational medicinal product code
    Other name
    LY3500518,AM0010
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Pegilodecakin 5 μg/kg dosed as one of the following 2 fixed doses: 0.4 mg for participants weighing ≤80 kg or 0.8 mg for participants weighing>80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. . After discontinuation of FOLFOX in the absence of tumor progression [that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing>80 kg.

    Investigational medicinal product name
    FOLFOX: Oxaliplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Oxaliplatin 85 mg/m2 given as IV infusion.

    Investigational medicinal product name
    FOLFOX: dl-Leucovorin/l-Leucovorinc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    dl-Leucovorin (dl-LV) 400 mg/m2 given as IV infusion on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.

    Investigational medicinal product name
    FOLFOX: 5-fluorouracil (5-FU)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    5-fluorouracil (5-FU) 400 mg/m2 bolus and a 5- FU 2400 mg/m2 continuous infusion over 46 to 48 hours given on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.

    Arm title
    FOLFOX
    Arm description
    FOLFOX (dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5- FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.
    Arm type
    Active comparator

    Investigational medicinal product name
    FOLFOX: dl-Leucovorin/l-Leucovorinc
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    dl-Leucovorin (dl-LV) 400 mg/m2 given as IV infusion on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.

    Investigational medicinal product name
    FOLFOX: Oxaliplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Oxaliplatin 85 mg/m2 given as IV infusion.

    Investigational medicinal product name
    FOLFOX: 5-fluorouracil (5-FU)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    5-fluorouracil (5-FU) 400 mg/m2 bolus and a 5- FU 2400 mg/m2 continuous infusion over 46 to 48 hours given on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.

    Number of subjects in period 1
    Pegilodecakin + FOLFOX FOLFOX
    Started
    283
    284
    Received at Least 1 Dose of Study Drug
    278
    251
    Safety population
    278
    251
    Completed
    230
    227
    Not completed
    53
    57
         Unknown, Not Collected
    7
    6
         Consent withdrawn by subject
    6
    13
         Sponsor Decision
    39
    38
         Lost to follow-up
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Pegilodecakin + FOLFOX
    Reporting group description
    Pegilodecakin 5 microgram per kilogram (μg/kg) dosed as one of the following 2 fixed doses: 0.4 milligram (mg) for participants weighing less than or equal to (≤) 80 kg or 0.8 mg for participants weighing greater than (>) 80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) plus FOLFOX [dl-Leucovorin (dl-LV) 400 milligram per meter square (mg/m2) and oxaliplatin 85 mg/m2 followed by bolus 5-fluorouracil (5-FU) 400 mg/m2 and a 46 to 48 hour infusion of 5- FU 2400 mg/m2] initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. After discontinuation of FOLFOX in the absence of tumor progression [that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing>80 kg.

    Reporting group title
    FOLFOX
    Reporting group description
    FOLFOX (dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5- FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.

    Reporting group values
    Pegilodecakin + FOLFOX FOLFOX Total
    Number of subjects
    283 284 567
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    63.8 ± 9.0 64.1 ± 9.9 -
    Gender categorical
    Units: Subjects
        Female
    135 132 267
        Male
    148 152 300
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    9 6 15
        Not Hispanic or Latino
    263 265 528
        Unknown or Not Reported
    11 13 24
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    1 0 1
        Asian
    59 55 114
        Native Hawaiian or Other Pacific Islander
    0 1 1
        Black or African American
    8 8 16
        White
    207 213 420
        More than one race
    0 0 0
        Unknown or Not Reported
    8 7 15
    Region of Enrollment
    Units: Subjects
        United States
    93 89 182
        United Kingdom
    5 4 9
        Spain
    42 31 73
        Canada
    2 7 9
        South Korea
    48 41 89
        Austria
    3 10 13
        Belgium
    17 19 36
        Taiwan
    5 10 15
        Poland
    8 5 13
        Italy
    28 39 67
        France
    9 2 11
        Australia
    14 16 30
        Germany
    9 11 20

    End points

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    End points reporting groups
    Reporting group title
    Pegilodecakin + FOLFOX
    Reporting group description
    Pegilodecakin 5 microgram per kilogram (μg/kg) dosed as one of the following 2 fixed doses: 0.4 milligram (mg) for participants weighing less than or equal to (≤) 80 kg or 0.8 mg for participants weighing greater than (>) 80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) plus FOLFOX [dl-Leucovorin (dl-LV) 400 milligram per meter square (mg/m2) and oxaliplatin 85 mg/m2 followed by bolus 5-fluorouracil (5-FU) 400 mg/m2 and a 46 to 48 hour infusion of 5- FU 2400 mg/m2] initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. After discontinuation of FOLFOX in the absence of tumor progression [that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing>80 kg.

    Reporting group title
    FOLFOX
    Reporting group description
    FOLFOX (dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5- FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.

    Primary: Overall Survival

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    End point title
    Overall Survival
    End point description
    Overall survival is defined as the time from date of randomization to the date of death (due to any cause). For participants whose last known status is alive at the data cutoff date for the analysis, time will be censored as the last contact date prior to the data cutoff date. Analysis population included all randomized participants. The number of participants censored were Pegilodecakin + FOLFOX = 63 and FOLFOX = 73.
    End point type
    Primary
    End point timeframe
    Randomization to date of death from any cause (Up to 36 Months)
    End point values
    Pegilodecakin + FOLFOX FOLFOX
    Number of subjects analysed
    283
    284
    Units: Months
        median (confidence interval 95%)
    5.78 (5.45 to 6.64)
    6.28 (5.62 to 7.39)
    Statistical analysis title
    Overall Survival
    Statistical analysis description
    The primary test to compare overall survival between treatment arms was the two-sided log-rank test, stratified by region and prior therapy. The estimate of the hazard ration (HR) - (Pegilodecakin + FOLFOX Arm / FOLFOX Arm) and the corresponding 95% CI was computed using a Cox proportional hazards model stratified by randomization stratification factors. Randomization stratification factors were based on the data recorded in interactive voice response system (IVRS).
    Comparison groups
    Pegilodecakin + FOLFOX v FOLFOX
    Number of subjects included in analysis
    567
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    = 0.6565
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.045
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.863
         upper limit
    1.265
    Notes
    [1] - The primary test to compare overall survival between treatment arms was the two-sided log-rank test, stratified by region and prior therapy. The estimate of the hazard ration (HR) - (Pegilodecakin + FOLFOX Arm / FOLFOX Arm) and the corresponding 95% CI was computed using a Cox proportional hazards model stratified by randomization stratification factors. Randomization stratification factors were based on the data recorded in interactive voice response system (IVRS).

    Secondary: Progression Free Survival

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    End point title
    Progression Free Survival
    End point description
    Progression free survival (PFS) is defined as the time from randomization to the date of the first documented tumor progression as determined by the investigator (per RECIST v1.1 criteria) or death due to any cause - whichever occurs first. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study drug) prior to objectively determined PD or death, PFS was censored at the date of the last objective progression-free disease assessment prior to start of postdiscontinuation chemotherapy. If a participant did not have a complete baseline disease assessment, then PFS was censored at the enrollment date, regardless whether or not objectively determined PD or death had been observed for the participant. Analysis population included all randomized participants. The number of participants censored were Pegilodecakin + FOLFOX = 45 and FOLFOX = 86.
    End point type
    Secondary
    End point timeframe
    Randomization to Progressive Disease (PD) or Date of Death (Up to 36 Months)
    End point values
    Pegilodecakin + FOLFOX FOLFOX
    Number of subjects analysed
    283
    284
    Units: Months
        median (confidence interval 95%)
    2.14 (1.94 to 3.38)
    2.10 (1.94 to 3.25)
    Statistical analysis title
    Progression Free Survival
    Statistical analysis description
    The estimate of hazard ratio (HR) was stratified by region and prior therapy.
    Comparison groups
    Pegilodecakin + FOLFOX v FOLFOX
    Number of subjects included in analysis
    567
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.8144
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.981
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.808
         upper limit
    1.19

    Secondary: Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] That Assessed by Investigator

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    End point title
    Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] That Assessed by Investigator
    End point description
    Participants with confirmed complete response (CR), confirmed partial response (PR), stable disease (SD), or progressive disease (PD) according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria, as well as participants with a not evaluable/tumor response unknown. CR: disappearance of all tumor lesions by investigator. Participants who discontinued study treatment (for reasons other than progression) before entering concurrent phase were considered to have non-evaluable response. Analysis population included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Randomization to PD (Up to 36 Months)
    End point values
    Pegilodecakin + FOLFOX FOLFOX
    Number of subjects analysed
    283
    284
    Units: percentage of participants
        number (not applicable)
    4.6
    5.6
    Statistical analysis title
    Percentage of Participants Achieving Complete Res
    Comparison groups
    Pegilodecakin + FOLFOX v FOLFOX
    Number of subjects included in analysis
    567
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.7044 [2]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Odds ratio (OR)
    Point estimate
    0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.4
         upper limit
    1.7
    Notes
    [2] - P-value is calculated by Exact Cochran-Mantel-Haenszel test stratified by the randomization strata Prior Therapy - interactive voice response system (IVRS), Geographic Region - IVRS.

    Secondary: Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)

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    End point title
    Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD): Disease Control Rate (DCR)
    End point description
    Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1 and assessed by investigators. Analysis population included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Randomization to Objective Progressive Disease or Start of New Anti-Cancer Therapy (Up To 36 Months)
    End point values
    Pegilodecakin + FOLFOX FOLFOX
    Number of subjects analysed
    283
    284
    Units: Percentage of participants
        number (not applicable)
    42.8
    36.6
    Statistical analysis title
    Percentage of Participants With a Best Overall Re
    Comparison groups
    Pegilodecakin + FOLFOX v FOLFOX
    Number of subjects included in analysis
    567
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1463 [3]
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Odds ratio (OR)
    Point estimate
    1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.9
         upper limit
    1.8
    Notes
    [3] - P-value is calculated by Exact Cochran-Mantel-Haenszel test stratified by the randomization strata Prior Therapy - interactive voice response system (IVRS), Geographic Region - IVRS.

    Secondary: Duration of Response (DOR)

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    End point title
    Duration of Response (DOR)
    End point description
    Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy. Analysis population included all randomized participants who achieved an objective response of CR or PR. The number of participants censored were Pegilodecakin + FOLFOX = 4 and FOLFOX = 7.
    End point type
    Secondary
    End point timeframe
    Randomization to Progressive Disease (PD) or Date of Death (Up to 36 Months)
    End point values
    Pegilodecakin + FOLFOX FOLFOX
    Number of subjects analysed
    13
    16
    Units: Months
        median (confidence interval 95%)
    4.99 (3.45 to 7.06)
    5.17 (3.75 to 5.72)
    Statistical analysis title
    Duration of Objective Response (DOR)
    Statistical analysis description
    The estimate of hazard ratio (HR) was stratified by region and prior therapy.
    Comparison groups
    Pegilodecakin + FOLFOX v FOLFOX
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.9952
    Method
    Log Rank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.008
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.37
         upper limit
    2.741

    Secondary: 12-Month Survival Rate

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    End point title
    12-Month Survival Rate
    End point description
    The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization. Analysis population included all randomized participants.
    End point type
    Secondary
    End point timeframe
    From randomization to until the date of first documented date of death from any cause within 12 months, assessed up to 15 months
    End point values
    Pegilodecakin + FOLFOX FOLFOX
    Number of subjects analysed
    283
    284
    Units: Percentage of participants
        number (confidence interval 95%)
    0.5 (0.1 to 2.7)
    2.1 (0.4 to 6.5)
    Statistical analysis title
    12-Month Survival Rate
    Comparison groups
    Pegilodecakin + FOLFOX v FOLFOX
    Number of subjects included in analysis
    567
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.2999
    Method
    Log Rank
    Parameter type
    Mean difference (final values)
    Point estimate
    -1.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.6
         upper limit
    1.4

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up To 18 Months
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Pegilodecakin + FOLFOX
    Reporting group description
    Pegilodecakin 5 microgram per kilogram (μg/kg) dosed as one of the following 2 fixed doses: 0.4 milligram (mg) for participants weighing ≤80 kg or 0.8 mg for participants weighing>80 kg on Days 1-5 and Days 8-12 subcutaneously (SC) plus FOLFOX [dl-Leucovorin (dl-LV) 400 milligram per meter square (mg/m2) and oxaliplatin 85 mg/m2 followed by bolus 5-fluorouracil (5-FU) 400 mg/m2 and a 46 to 48 hour infusion of 5- FU 2400 mg/m2] initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression. After discontinuation of FOLFOX in the absence of tumor progression [that is (i.e., completion of the planned 12 cycles or unacceptable FOLFOX related toxicity], Pegilodecakin 10µg/kg maintenance treatment administered as one of the 2 fixed doses, either 0.8 mg for participants weighing ≤80 kg or 1.6 mg for participants weighing>80 kg.

    Reporting group title
    FOLFOX
    Reporting group description
    FOLFOX (dl-LV 400 mg/m2 and oxaliplatin 85 mg/m2 followed by bolus 5- FU 400 mg/m2 and a 46-hour infusion of 5-FU 2400 mg/m2) initiated on Day 1 of a 14-day cycles for up to 12 cycles or until disease progression.

    Serious adverse events
    Pegilodecakin + FOLFOX FOLFOX
    Total subjects affected by serious adverse events
         subjects affected / exposed
    123 / 278 (44.24%)
    95 / 251 (37.85%)
         number of deaths (all causes)
    14
    7
         number of deaths resulting from adverse events
    2
    0
    Vascular disorders
    aortic embolus
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    deep vein thrombosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    embolism
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    internal haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    peripheral coldness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    acute myeloid leukaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tumour pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    anaphylactic reaction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    euthanasia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    general physical health deterioration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    generalised oedema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperpyrexia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    malaise
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    mucosal inflammation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    multiple organ dysfunction syndrome
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oedema peripheral
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    13 / 278 (4.68%)
    7 / 251 (2.79%)
         occurrences causally related to treatment / all
    6 / 15
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    completed suicide
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    mental status changes
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    suicide attempt
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (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
    prostatic obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed [1]
    1 / 144 (0.69%)
    0 / 134 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    craniocerebral injury
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    fibula fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hip fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    infusion related reaction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    overdose
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    tibia fracture
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    blood bilirubin increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    4 / 251 (1.59%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutrophil count decreased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    platelet count decreased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    angina pectoris
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    atrial fibrillation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cardiac arrest
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    cardiac failure acute
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    acute respiratory distress syndrome
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    asthma
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    chronic obstructive pulmonary disease
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pneumonitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    3 / 251 (1.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory acidosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (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
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    1 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    3 / 251 (1.20%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    cerebral ischaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    cerebrovascular accident
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lethargy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    metabolic encephalopathy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    neuropathy peripheral
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sciatica
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    transient ischaemic attack
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    11 / 278 (3.96%)
    3 / 251 (1.20%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain lower
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    abdominal pain upper
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ascites
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    colitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    constipation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    5 / 251 (1.99%)
         occurrences causally related to treatment / all
    0 / 3
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    duodenal obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    duodenal stenosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    duodenal ulcer haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dyspepsia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastric haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroduodenal ulcer
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastrointestinal stenosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    haematemesis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ileal perforation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    3 / 251 (1.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    large intestinal obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    obstruction gastric
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oesophageal stenosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pancreatitis acute
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    small intestinal obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    stomatitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    upper gastrointestinal haemorrhage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    7 / 278 (2.52%)
    5 / 251 (1.99%)
         occurrences causally related to treatment / all
    2 / 8
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cystitis haemorrhagic
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    nephrolithiasis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    oliguria
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    renal failure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urinary tract obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    bile duct obstruction
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bile duct stenosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholangitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    6 / 278 (2.16%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cholangitis acute
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholecystitis acute
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic cirrhosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic function abnormal
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hepatic pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    jaundice cholestatic
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    3 / 251 (1.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Skin and subcutaneous tissue disorders
    rash maculo-papular
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    device breakage
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device failure
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device occlusion
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    back pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    3 / 251 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bursitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    flank pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    muscular weakness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    musculoskeletal pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    adult failure to thrive
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    cachexia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    decreased appetite
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    dehydration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diabetes mellitus
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diabetic ketoacidosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diabetic metabolic decompensation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    failure to thrive
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypercalcaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyperglycaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hypokalaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    hyponatraemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lactic acidosis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    abdominal sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    bacteraemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    bacterial disease carrier
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    biliary sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    2 / 251 (0.80%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    biliary tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    3 / 278 (1.08%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cellulitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    cholangitis infective
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    clostridium difficile colitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    2 / 278 (0.72%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 278 (1.44%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    device related sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    diverticulitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    enterobacter sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    enterocolitis infectious
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    escherichia sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    gastroenteritis norovirus
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    klebsiella sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    liver abscess
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    lower respiratory tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    peritonsillar abscess
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumococcal sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumocystis jirovecii pneumonia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    7 / 278 (2.52%)
    4 / 251 (1.59%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    pneumonia cryptococcal
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    sepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    10 / 278 (3.60%)
    4 / 251 (1.59%)
         occurrences causally related to treatment / all
    2 / 10
    0 / 4
         deaths causally related to treatment / all
    2 / 2
    0 / 1
    septic shock
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    4 / 278 (1.44%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    urosepsis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    0 / 278 (0.00%)
    1 / 251 (0.40%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    viral infection
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    1 / 278 (0.36%)
    0 / 251 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Gender specific events only occurring in male or female participants have had the number of participants at risk adjusted accordingly.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Pegilodecakin + FOLFOX FOLFOX
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    271 / 278 (97.48%)
    240 / 251 (95.62%)
    Investigations
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    12 / 278 (4.32%)
    14 / 251 (5.58%)
         occurrences all number
    17
    22
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    21 / 278 (7.55%)
    15 / 251 (5.98%)
         occurrences all number
    28
    20
    blood bilirubin increased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    19 / 278 (6.83%)
    10 / 251 (3.98%)
         occurrences all number
    28
    12
    neutrophil count decreased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    47 / 278 (16.91%)
    30 / 251 (11.95%)
         occurrences all number
    84
    51
    platelet count decreased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    59 / 278 (21.22%)
    26 / 251 (10.36%)
         occurrences all number
    163
    51
    weight decreased
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    14 / 278 (5.04%)
    25 / 251 (9.96%)
         occurrences all number
    17
    34
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    17 / 278 (6.12%)
    19 / 251 (7.57%)
         occurrences all number
    22
    22
    dyspnoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    30 / 278 (10.79%)
    15 / 251 (5.98%)
         occurrences all number
    41
    17
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    107 / 278 (38.49%)
    38 / 251 (15.14%)
         occurrences all number
    204
    56
    neutropenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    58 / 278 (20.86%)
    41 / 251 (16.33%)
         occurrences all number
    118
    65
    thrombocytopenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    99 / 278 (35.61%)
    28 / 251 (11.16%)
         occurrences all number
    296
    42
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    19 / 278 (6.83%)
    8 / 251 (3.19%)
         occurrences all number
    23
    9
    dysgeusia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    19 / 278 (6.83%)
    9 / 251 (3.59%)
         occurrences all number
    22
    11
    headache
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    18 / 278 (6.47%)
    17 / 251 (6.77%)
         occurrences all number
    24
    20
    neuropathy peripheral
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    40 / 278 (14.39%)
    38 / 251 (15.14%)
         occurrences all number
    50
    62
    neurotoxicity
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    13 / 278 (4.68%)
    15 / 251 (5.98%)
         occurrences all number
    25
    30
    paraesthesia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    24 / 278 (8.63%)
    17 / 251 (6.77%)
         occurrences all number
    34
    44
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    31 / 278 (11.15%)
    29 / 251 (11.55%)
         occurrences all number
    48
    35
    polyneuropathy
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    9 / 278 (3.24%)
    14 / 251 (5.58%)
         occurrences all number
    13
    25
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    76 / 278 (27.34%)
    45 / 251 (17.93%)
         occurrences all number
    151
    105
    fatigue
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    105 / 278 (37.77%)
    74 / 251 (29.48%)
         occurrences all number
    181
    108
    injection site erythema
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    18 / 278 (6.47%)
    0 / 251 (0.00%)
         occurrences all number
    18
    0
    oedema peripheral
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    41 / 278 (14.75%)
    22 / 251 (8.76%)
         occurrences all number
    49
    25
    pyrexia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    56 / 278 (20.14%)
    36 / 251 (14.34%)
         occurrences all number
    82
    51
    Psychiatric disorders
    insomnia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    14 / 278 (5.04%)
    13 / 251 (5.18%)
         occurrences all number
    14
    13
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    18 / 278 (6.47%)
    14 / 251 (5.58%)
         occurrences all number
    22
    15
    abdominal pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    82 / 278 (29.50%)
    58 / 251 (23.11%)
         occurrences all number
    114
    82
    abdominal pain upper
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    20 / 278 (7.19%)
    14 / 251 (5.58%)
         occurrences all number
    34
    17
    ascites
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    28 / 278 (10.07%)
    19 / 251 (7.57%)
         occurrences all number
    35
    20
    constipation
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    79 / 278 (28.42%)
    59 / 251 (23.51%)
         occurrences all number
    93
    70
    diarrhoea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    70 / 278 (25.18%)
    71 / 251 (28.29%)
         occurrences all number
    104
    101
    dyspepsia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    21 / 278 (7.55%)
    14 / 251 (5.58%)
         occurrences all number
    23
    16
    flatulence
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    14 / 278 (5.04%)
    4 / 251 (1.59%)
         occurrences all number
    15
    6
    nausea
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    126 / 278 (45.32%)
    106 / 251 (42.23%)
         occurrences all number
    217
    160
    stomatitis
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    27 / 278 (9.71%)
    40 / 251 (15.94%)
         occurrences all number
    37
    48
    vomiting
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    80 / 278 (28.78%)
    69 / 251 (27.49%)
         occurrences all number
    122
    106
    Skin and subcutaneous tissue disorders
    pruritus
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    15 / 278 (5.40%)
    8 / 251 (3.19%)
         occurrences all number
    24
    11
    rash
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    23 / 278 (8.27%)
    9 / 251 (3.59%)
         occurrences all number
    34
    10
    Musculoskeletal and connective tissue disorders
    back pain
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    37 / 278 (13.31%)
    32 / 251 (12.75%)
         occurrences all number
    44
    39
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    97 / 278 (34.89%)
    77 / 251 (30.68%)
         occurrences all number
    132
    100
    dehydration
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    12 / 278 (4.32%)
    14 / 251 (5.58%)
         occurrences all number
    22
    19
    hyperglycaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    14 / 278 (5.04%)
    10 / 251 (3.98%)
         occurrences all number
    20
    11
    hypoalbuminaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    20 / 278 (7.19%)
    10 / 251 (3.98%)
         occurrences all number
    28
    11
    hypokalaemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    21 / 278 (7.55%)
    29 / 251 (11.55%)
         occurrences all number
    37
    39
    hyponatraemia
    alternative dictionary used: MedDRA 23.0
         subjects affected / exposed
    11 / 278 (3.96%)
    16 / 251 (6.37%)
         occurrences all number
    15
    21

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Jun 2017
    - Inclusion and exclusion criteria updated. - Weight based dosing for treatment with pegilodecakin updated. - Updated when and how SAEs/ suspected unexpected serious adverse reactions (SUSARs) were captured.
    19 Jul 2017
    - Inclusion and exclusion criteria updated. - Contraception use guideline revised. - Weight based dosing for treatment with pegilodecakin updated. - Reporting of serious adverse events updated and definition of SUSAR added. - Planned hospitalization not to be designated as an serious adverse event.
    15 May 2018
    - Changes to the inclusion/exclusion criteria. - New strength of pegilodecakin added. - Pegilodecakin container closure system changed.
    05 Oct 2018
    - Secondary objectives and endpoints added. - Study design was updated to allow continued access. - Inclusion criteria updated. - Censoring guidance for PFS changed. - Subgroup and sensitivity analysis plan added.

    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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