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    Clinical Trial Results:
    A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of CNTO 328 (Anti IL-6 Monoclonal Antibody) Plus Best Supportive Care Compared With Best Supportive Care in Subjects With Multicentric Castleman’s Disease

    Summary
    EudraCT number
    2009-012380-34
    Trial protocol
    GB   BE   ES   DE   FR   NL   HU  
    Global end of trial date
    24 Feb 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    11 Mar 2018
    First version publication date
    11 Mar 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CNTO328MCD2001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01024036
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Research & Development, LLC
    Sponsor organisation address
    920 Route 202, Raritan, United States, NJ 08869
    Public contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Research & Development, LLC, ClinicalTrialsEU@its.jnj.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
    24 Feb 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Feb 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of the study was to demonstrate that siltuximab in combination with best supportive care (BSC) was superior to BSC in terms of durable tumor and symptomatic response among subjects with Multicentric Castleman’s Disease (MCD).
    Protection of trial subjects
    This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements. Safety was evaluated throughout the study and included adverse events (AEs), SAEs, routine clinical laboratory tests (hematology, chemistry, and coagulation), vital signs, ECGs, weight, infusion related reactions, and measurement for antibodies to study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 Feb 2010
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    4 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Brazil: 6
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    China: 16
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Egypt: 1
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Hong Kong: 5
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Norway: 2
    Country: Number of subjects enrolled
    New Zealand: 2
    Country: Number of subjects enrolled
    Russian Federation: 3
    Country: Number of subjects enrolled
    Singapore: 3
    Country: Number of subjects enrolled
    Taiwan: 4
    Country: Number of subjects enrolled
    United States: 14
    Worldwide total number of subjects
    79
    EEA total number of subjects
    15
    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)
    75
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    79 subjects were enrolled at 38 study centers in 19 countries. The first subject signed the informed consent on 09 Feb 2010, and the last subject's last visit for the primary analysis was 28 Feb 2013. The data until the end of study is presented here.

    Pre-assignment
    Screening details
    79 subjects were enrolled, randomized and treated during the blinded treatment period. 53 received siltuximab+best supportive care (BSC) and 26 received placebo+BSC.13 subjects who did not respond to placebo+BSC during the blinded treatment period, received siltuximab+BSC during the unblinded treatment period.

    Period 1
    Period 1 title
    Blinded Treatment
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Siltuximab + Best Supportive Care (BSC)
    Arm description
    Subjects received siltuximab 11 milligram per kilogram (mg/kg) as a 1-hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. Subjects who discontinued treatment for any reason completed End-of-Treatment (EOT) Visit and entered Follow-up Period. If a subject had documented treatment failure and wished to continue treatment, subject’s treatment assignment was to be unblinded. Upon unblinding, if subejcts assigned to siltuximab, study treatment was to be discontinued, and the subject was to complete EOT Visit and enter Follow-up Period (up to 3 months after last study drug intake) wherein subjects were not received any study treatment and were followed until death, lost to follow up, withdrawal of consent, death of 50 percentage (%) of subjects, or end of the study, whichever occurred earlier.
    Arm type
    Experimental

    Investigational medicinal product name
    Siltuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received siltuximab 11 mg/kg as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier.

    Arm title
    Placebo + Best Supportive Care (BSC)
    Arm description
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. If a subject had documented treatment failure and wished to continue treatment, the subject’s treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein subjects were followed until death, lost to follow-up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier.

    Number of subjects in period 1
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Started
    53
    26
    Completed
    31
    6
    Not completed
    22
    20
         Physician decision
    1
    -
         Lack of efficacy
    16
    14
         Adverse event, serious fatal
    -
    2
         Adverse event, non-fatal
    1
    1
         Consent withdrawn by subject
    4
    3
    Period 2
    Period 2 title
    Unblinded Treatment
    Is this the baseline period?
    No
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Placebo + Best Supportive Care (BSC)
    Arm description
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. If a subject had documented treatment failure and wished to continue treatment, the subject’s treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein subjects were followed until death, lost to follow-up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.
    Arm type
    Experimental

    Investigational medicinal product name
    Siltuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects assigned to placebo crossover to siltuximab and received siltuximab 11 mg/kg as a 1-hour IV infusion every 3 weeks along with BSC.

    Number of subjects in period 2 [1]
    Placebo + Best Supportive Care (BSC)
    Started
    13
    Completed
    10
    Not completed
    3
         Lack of efficacy
    2
         Adverse event, non-fatal
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Placebo subjects who had documented treatment failure and wished to continue treatment had an option to receive siltuximab during the unblinded treatment period.
    Period 3
    Period 3 title
    Follow-up Period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    No

    Arm title
    Siltuximab + Best Supportive Care (BSC)
    Arm description
    Subjects received siltuximab 11 mg/kg as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. Subjects who discontinued treatment for any reason completed End-of-Treatment (EOT) Visit and entered Follow-up Period. If a subject had documented treatment failure and wished to continue treatment, subject’s treatment assignment was to be unblinded. Upon unblinding, if subejcts assigned to siltuximab, study treatment was to be discontinued, and the subject was to complete EOT Visit and enter Follow-up Period (up to 3 months after last study drug intake) wherein subjects were not received any study treatment and were followed until death, lost to follow up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.
    Arm type
    Experimental

    Investigational medicinal product name
    Siltuximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received siltuximab (11 mg/kg every 3 weeks) in the treatment period were followed up (up to 3 months after last study drug intake) until death, lost to follow up, withdrawal of consent, death of 50 percentage (%) of subjects, or end of the study, whichever occurred earlier.

    Arm title
    Placebo + Best Supportive Care (BSC)
    Arm description
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. If a subject had documented treatment failure and wished to continue treatment, the subject’s treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein subjects were followed until death, lost to follow-up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects received matching placebo in the treatment period were continued to be followed up in follow-up period (up to 3 months after last study drug intake) until death, lost to follow up, withdrawal of consent, death of 50% of subjects, or the end of the study, whichever occurred earlier.

    Number of subjects in period 3
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Started
    14
    6
    Completed
    9
    3
    Not completed
    5
    3
         Adverse event, serious fatal
    4
    1
         Consent withdrawn by subject
    -
    1
         Lost to follow-up
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Siltuximab + Best Supportive Care (BSC)
    Reporting group description
    Subjects received siltuximab 11 milligram per kilogram (mg/kg) as a 1-hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. Subjects who discontinued treatment for any reason completed End-of-Treatment (EOT) Visit and entered Follow-up Period. If a subject had documented treatment failure and wished to continue treatment, subject’s treatment assignment was to be unblinded. Upon unblinding, if subejcts assigned to siltuximab, study treatment was to be discontinued, and the subject was to complete EOT Visit and enter Follow-up Period (up to 3 months after last study drug intake) wherein subjects were not received any study treatment and were followed until death, lost to follow up, withdrawal of consent, death of 50 percentage (%) of subjects, or end of the study, whichever occurred earlier.

    Reporting group title
    Placebo + Best Supportive Care (BSC)
    Reporting group description
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. If a subject had documented treatment failure and wished to continue treatment, the subject’s treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein subjects were followed until death, lost to follow-up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.

    Reporting group values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC) Total
    Number of subjects
    53 26 79
    Title for AgeCategorical
    Units: subjects
        Adults (18-64 years)
    51 24 75
        From 65 to 84 years
    2 2 4
        85 years and over
    0 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    44.4 ± 13.32 47.7 ± 13.4 -
    Title for Gender
    Units: subjects
        Female
    23 4 27
        Male
    30 22 52

    End points

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    End points reporting groups
    Reporting group title
    Siltuximab + Best Supportive Care (BSC)
    Reporting group description
    Subjects received siltuximab 11 milligram per kilogram (mg/kg) as a 1-hour intravenous (IV) infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. Subjects who discontinued treatment for any reason completed End-of-Treatment (EOT) Visit and entered Follow-up Period. If a subject had documented treatment failure and wished to continue treatment, subject’s treatment assignment was to be unblinded. Upon unblinding, if subejcts assigned to siltuximab, study treatment was to be discontinued, and the subject was to complete EOT Visit and enter Follow-up Period (up to 3 months after last study drug intake) wherein subjects were not received any study treatment and were followed until death, lost to follow up, withdrawal of consent, death of 50 percentage (%) of subjects, or end of the study, whichever occurred earlier.

    Reporting group title
    Placebo + Best Supportive Care (BSC)
    Reporting group description
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. If a subject had documented treatment failure and wished to continue treatment, the subject’s treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein subjects were followed until death, lost to follow-up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.
    Reporting group title
    Placebo + Best Supportive Care (BSC)
    Reporting group description
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. If a subject had documented treatment failure and wished to continue treatment, the subject’s treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein subjects were followed until death, lost to follow-up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.
    Reporting group title
    Siltuximab + Best Supportive Care (BSC)
    Reporting group description
    Subjects received siltuximab 11 mg/kg as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. Subjects who discontinued treatment for any reason completed End-of-Treatment (EOT) Visit and entered Follow-up Period. If a subject had documented treatment failure and wished to continue treatment, subject’s treatment assignment was to be unblinded. Upon unblinding, if subejcts assigned to siltuximab, study treatment was to be discontinued, and the subject was to complete EOT Visit and enter Follow-up Period (up to 3 months after last study drug intake) wherein subjects were not received any study treatment and were followed until death, lost to follow up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.

    Reporting group title
    Placebo + Best Supportive Care (BSC)
    Reporting group description
    Subjects received placebo as a 1-hour IV infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from study, or until 48 weeks after last subject started study treatment, whichever occurred earlier. If a subject had documented treatment failure and wished to continue treatment, the subject’s treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period (up to 3 months after last study drug intake) wherein subjects were followed until death, lost to follow-up, withdrawal of consent, death of 50% of subjects, or end of the study, whichever occurred earlier.

    Primary: Percentage of Subjects Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review

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    End point title
    Percentage of Subjects Who Achieved Durable Tumor and Symptomatic Response - by Independent Radiology Review
    End point description
    Durable tumor and symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman’s disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks. The statistical analysis shows difference in symptomatic response rate (siltuximab+best supportive care [BSC] minus Placebo+BSC). Intent-to-treat (ITT) population: all randomized subjects.
    End point type
    Primary
    End point timeframe
    From Day 1 of Cycle 1 of treatment with study medication until treatment failure or discontinuation of treatment or withdrawal from study, or up to 48 weeks after last subject started study medication (approximately 3 years), whichever occurred earlier
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    53
    26
    Units: Percentage of subjects
        number (not applicable)
    34
    0
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Placebo + Best Supportive Care (BSC) v Siltuximab + Best Supportive Care (BSC)
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0012
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    difference in the response rate
    Point estimate
    34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.1
         upper limit
    54.8
    Statistical analysis title
    Statistical Analysis 2
    Comparison groups
    Placebo + Best Supportive Care (BSC) v Siltuximab + Best Supportive Care (BSC)
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0004
    Method
    Fisher exact
    Parameter type
    difference in the response rate
    Point estimate
    34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.1
         upper limit
    54.8

    Secondary: Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review

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    End point title
    Median Duration of Tumor and Symptomatic Response - by Independent Radiology Review
    End point description
    Duration of tumor and symptomatic response is defined as time from first documentation of tumor and symptomatic response (CR or PR) to treatment failure. Whenever possible, treatment failure documented by the appearance of new lesions should be confirmed by histologic examination of the new lesions. Symptomatic response is complete response (CR) + partial response (PR). CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion) and resolution of baseline symptoms attributed to multicentric Castleman’s disease, sustained for at least 18 weeks. PR: >=50 percent decrease in sum of the product of the diameters of indicator lesion(s), with at least stable disease in all other evaluable disease in the absence of treatment failure sustained for at least 18 weeks. Population analyzed included all randomized subjects who achieved durable tumor and symptomatic response during blinded treatment period as per independent review.
    End point type
    Secondary
    End point timeframe
    From the date when durable tumour and symptomatic response is achieved until treatment failure, as assessed until 48 weeks after the last subject started study treatment (approximately 3 years)
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    18
    0 [1]
    Units: Days
        median (full range (min-max))
    383.0 (232 to 676)
    ( to )
    Notes
    [1] - Number of Subjects Analyzed were 0 because none of the subject showed a response.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review

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    End point title
    Percentage of Subjects Who Achieved Complete Response (CR) + Partial Response (PR) (Tumor Response Rate) - by Independent Radiology Review
    End point description
    Overall tumor response is CR + PR assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a >=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care [BSC] minus Placebo+BSC). Response-evaluable Population included subjects who received at least 1 administration of siltuximab/placebo and had at least 1 post-baseline radiologic disease evaluation.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Cycle 1 until the date when durable tumour and symptomatic response is achieved, as assessed up to 48 weeks after the last subject started study treatment (approximately 3 years)
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    53
    26
    Units: Percentage of subjects
        number (not applicable)
    37.7
    3.8
    Statistical analysis title
    Statistical Analysis
    Comparison groups
    Siltuximab + Best Supportive Care (BSC) v Placebo + Best Supportive Care (BSC)
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0022
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference in overall response rates
    Point estimate
    33.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.1
         upper limit
    54.8

    Secondary: Median Duration of Tumor Response - by Independent Radiology Review

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    End point title
    Median Duration of Tumor Response - by Independent Radiology Review
    End point description
    Duration of tumor response is defined as time from first documentation of tumor response to tumor progression. Tumour response is complete response (CR) + partial response (PR) as assessed according to Cheson criteria. CR: complete disappearance of all measurable and evaluable disease (eg, pleural effusion). PR: a >=50 percent decrease in sum of the product of the diameters of index lesion(s), with at least stable disease in all other evaluable disease. Statistical analysis shows difference of overall response rates (siltuximab+best supportive care [BSC] minus Placebo+BSC). Population analyzed included all randomized subjects who achieved tumor response during blinded treatment period as per independent review.
    End point type
    Secondary
    End point timeframe
    From the date when tumour response is achieved until tumour progression, as assessed up to 48 weeks after the last subject started study treatment (approximately 3 years)
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    20
    1
    Units: Days
        median (full range (min-max))
    356.0 (55 to 674)
    70.0 (70 to 70)
    No statistical analyses for this end point

    Secondary: Time to Treatment Failure

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    End point title
    Time to Treatment Failure
    End point description
    Time to treatment failure was defined as the time from randomization until the subjects fails treatment. Treatment failure was defined as any of the following: a sustained increase from baseline in disease related symptoms >=Grade 2 persisting for at least 3 weeks despite BSC; onset of any new disease related Grade 3 or higher symptom despite BSC; sustained (ie, at least 3 weeks) deterioration in performance status (increase from baseline in ECOG Performance Status by more than 1 point) despite BSC; radiologic progression, as per Cheson criteria; Initiation of any other therapy intended to treat multicentric Castleman’s disease ie, prohibited treatments. ITT population included all randomized subjects. Here, 99999 in siltuximab arm signifies median time to treatment failure that was not estimable and in placebo arm it signifies upper limit that was not estimable due to insufficient number of subjects with event.
    End point type
    Secondary
    End point timeframe
    From the date of randomization until a subject fails treatment, as assessed up to 48 weeks after the last subject started study treatment (approximately 3 years), whichever occurred earlier
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    53
    26
    Units: Days
        median (confidence interval 95%)
    99999 (378 to 99999)
    134.0 (85 to 99999)
    Statistical analysis title
    Statistical Analysis
    Comparison groups
    Siltuximab + Best Supportive Care (BSC) v Placebo + Best Supportive Care (BSC)
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0084
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.418
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.214
         upper limit
    0.815

    Secondary: Percentage of Subjects Who Achieved Greater Than or Equal to (>=) 15 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)

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    End point title
    Percentage of Subjects Who Achieved Greater Than or Equal to (>=) 15 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)
    End point description
    Hemoglobin response rate is defined as percentage of subjects who achieved >= 15 g/L hemoglobin at Week 13. Hemoglobin response-evaluable population: subjects who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 postbaseline hemoglobin evaluation.
    End point type
    Secondary
    End point timeframe
    Week 13
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    31
    11
    Units: Percentage of subjects
        number (not applicable)
    61.3
    0
    Statistical analysis title
    Statistical Analysis
    Comparison groups
    Siltuximab + Best Supportive Care (BSC) v Placebo + Best Supportive Care (BSC)
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0002
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference of hemoglobin response rates
    Point estimate
    61.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    28.3
         upper limit
    85.1

    Secondary: Percentage of Subjects Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)

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    End point title
    Percentage of Subjects Who Achieved >= 20 g/L Hemoglobin at Week 13 (Hemoglobin Response Rate)
    End point description
    Hemoglobin response rate is defined as percentage of subjects who achieved >= 20 g/L hemoglobin at Week 13. Hemoglobin response-evaluable population: subjects who received at least 1 siltuximab/placebo administration and have a baseline hemoglobin that is below the lower limit of normal as per local laboratory specifications (within 2 weeks before starting treatment) and at least 1 post-baseline hemoglobin evaluation.
    End point type
    Secondary
    End point timeframe
    Week 13
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    31
    11
    Units: Percentage of subjects
        number (not applicable)
    41.9
    0
    Statistical analysis title
    Statistical Analysis
    Comparison groups
    Siltuximab + Best Supportive Care (BSC) v Placebo + Best Supportive Care (BSC)
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.0195
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Difference of hemoglobin response rates
    Point estimate
    41.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.8
         upper limit
    70.7

    Secondary: Percentage of Subjects Who Discontinued Corticosteroids

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    End point title
    Percentage of Subjects Who Discontinued Corticosteroids
    End point description
    Percentage of subjects who discontinued corticosteroids during blinded treatment period and who were dependent on corticosteroids at baseline (Day 1 of Cycle 1). Population analyzed included all randomized subjects who were dependent on corticosteroids at baseline.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Cycle 1 until 48 weeks after the after the last subject started study treatment (approximately 3 years)
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    13
    9
    Units: Percentage of subjects
        number (not applicable)
    30.8
    11.1
    No statistical analyses for this end point

    Secondary: 6-Year Survival Rate

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    End point title
    6-Year Survival Rate
    End point description
    Overall survival was defined as percent chance of survival of subjects who were still alive at 6 years from time of first study treatment was analyzed. Safety Analysis set included all subjects who received at least 1 dose of study agent were included in the safety analysis.
    End point type
    Secondary
    End point timeframe
    until 6 years
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    53
    26
    Units: Percent chance of survival
        median (confidence interval 95%)
    86.3 (71.9 to 93.6)
    79.5 (57.5 to 91.0)
    No statistical analyses for this end point

    Secondary: Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman’s Disease Symptom Scale (MCD-SS) Score From Baseline

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    End point title
    Median Time Required to Achieve >=1 Point Decrease in the Multicentric Castleman’s Disease Symptom Scale (MCD-SS) Score From Baseline
    End point description
    A patient-reported symptom scale. Symptom presence/absence and severity are noted on an anchor-based numeric scale. Scores range from 1 (very mild) to 5 (very severe). Intent-to-treat (ITT) population included all randomized subjects. Here, 99999 signifies that upper limit was not estimable due to insufficient number of subjects with event.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Cycle 1 (baseline) until 48 weeks after the last subject started study treatment (approximately 3 years)
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    51
    26
    Units: Days
        median (full range (min-max))
    85.0 (22 to 379)
    262.0 (40 to 99999)
    No statistical analyses for this end point

    Secondary: Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline

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    End point title
    Median Time Required to Achieve >=3-point Increase in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scores From Baseline
    End point description
    The FACIT-F, a 13-item instrument, was designed to measure patient-reported fatigue. It is one of the suite of FACIT instruments developed for outcomes in cancer. Concepts measured in the scale include tiredness, weakness, and difficulty conducting usual functional activities or social interaction due to fatigue. Response options range from “not at all” (0) to “very much” (4), and yield a summary score. Total FACIT-F score is the sum of 13 items, ranging from 0 (not at all) to 52 (very much). Higher scores represent better outcomes. Intent-to-treat (ITT) population included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Cycle 1 (baseline) until 48 weeks after the last subject started study treatment (approximately 3 years)
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    53
    26
    Units: Days
        median (confidence interval 95%)
    15 (8 to 23)
    22 (8 to 64)
    No statistical analyses for this end point

    Secondary: Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline

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    End point title
    Median Time Required to Achieve >=5-point Increase in the Short-Form-36 (SF-36) Physical Component Summary (PCS) Scores From Baseline
    End point description
    SF-36 is a questionnaire and PCS is a part of subscale assessing physical functioning, role-physical, bodily pain, and general health. The scores range from 0 (worst score) to 100 (best score), with a higher score indicating better quality of life. Intent-to-treat (ITT) population included all randomized subjects. Here, 99999 in siltuximab arm signifies that the upper limit was not estimable due to insufficient number of subjects with event while in placebo arm signifies median time was not estimable due to insufficient number of subjects with event.
    End point type
    Secondary
    End point timeframe
    From Day 1 of Cycle 1 (baseline) until 48 weeks after the last subject started study treatment (approximately 3 years)
    End point values
    Siltuximab + Best Supportive Care (BSC) Placebo + Best Supportive Care (BSC)
    Number of subjects analysed
    53
    26
    Units: Days
        median (confidence interval 95%)
    420 (106 to 99999)
    99999 (169 to 99999)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 7 years
    Adverse event reporting additional description
    Safety Analysis set included, subjects who received at least 1 dose of study drug in blinded and unblinded treatment until 48 weeks after last subject started study treatment (approximately 3 years). Follow-up analysis set included subjects who continued in study from Week 48 till end-of-study (5 years after last subject started study treatment).
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Placebo + Best Supportive Care (BSC) (Blinded)
    Reporting group description
    Subjects received placebo as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last subject started study treatment, whichever occurred earlier. Subjects who discontinued or completed treatment period up to Week 48 and who consented to enter follow-up period were continued to be followed up during the course of follow-up period.

    Reporting group title
    Siltuximab + Best Supportive Care (BSC) (Blinded)
    Reporting group description
    Subjects received siltuximab 11mg/kg as a 1-hour intravenous infusion every 3 weeks along with BSC until treatment failure, discontinuation of treatment, withdrawal from the study, or until 48 weeks after the last subject started study treatment, whichever occurred earlier. Subjects who discontinued treatment for any reason completed the end-of-treatment visit and entered the follow-up period.

    Reporting group title
    Siltuximab + Best Supportive Care (BSC) (Unblinded)
    Reporting group description
    Subjects who had documented treatment failure and wished to continue treatment, their treatment assignment was unblinded. Upon unblinding placebo subjects who received blinded treatment had an option to receive unblinded treatment with siltuximab during the unblinded treatment period.

    Reporting group title
    Placebo + BSC (Follow-up Period)
    Reporting group description
    No study treatment was administered during the follow-up period (up to 3 months after last study agent administration [placebo as a 1 hour IV infusion every 3 weeks along with BSC]) and subjects were followed until death, lost to follow up, withdrawal of consent, death of 50 % of subjects, or the end of the study, whichever occurred earlier.

    Reporting group title
    Siltuximab + BSC (Follow-up Period)
    Reporting group description
    No study treatment was administered during the follow-up period (up to 3 months after last study agent administration [siltuximab 11mg/kg as a 1 hour IV infusion every 3 weeks along with ]) and subjects were followed until death, lost to follow up, withdrawal of consent, death of 50 % of subjects, or the end of the study, whichever occurred earlier.

    Serious adverse events
    Placebo + Best Supportive Care (BSC) (Blinded) Siltuximab + Best Supportive Care (BSC) (Blinded) Siltuximab + Best Supportive Care (BSC) (Unblinded) Placebo + BSC (Follow-up Period) Siltuximab + BSC (Follow-up Period)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 26 (26.92%)
    12 / 53 (22.64%)
    4 / 13 (30.77%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         number of deaths (all causes)
    5
    6
    0
    1
    4
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertensive Crisis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Pain Management
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Poems Syndrome
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    T-Cell Lymphoma
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic Reaction
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Oedema
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema Peripheral
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tibia Fracture
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound Secretion
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Mycobacterium Test
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac Failure Congestive
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 4
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 53 (1.89%)
    2 / 13 (15.38%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Vitreous Haemorrhage
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical Hernia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis Chronic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal Colic
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ureteral Disorder
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscle Spasms
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal Abscess
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo + Best Supportive Care (BSC) (Blinded) Siltuximab + Best Supportive Care (BSC) (Blinded) Siltuximab + Best Supportive Care (BSC) (Unblinded) Placebo + BSC (Follow-up Period) Siltuximab + BSC (Follow-up Period)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 26 (96.15%)
    53 / 53 (100.00%)
    13 / 13 (100.00%)
    5 / 6 (83.33%)
    14 / 14 (100.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 53 (3.77%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    2
    2
    0
    0
    Haemorrhage
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Hypertension
         subjects affected / exposed
    3 / 26 (11.54%)
    4 / 53 (7.55%)
    3 / 13 (23.08%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    5
    7
    5
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour Pain
         subjects affected / exposed
    4 / 26 (15.38%)
    4 / 53 (7.55%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    6
    6
    4
    0
    2
    Immune system disorders
    Seasonal Allergy
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 53 (3.77%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    2
    1
    0
    0
    General disorders and administration site conditions
    Chest Discomfort
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Chest Pain
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    Chills
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Face Oedema
         subjects affected / exposed
    1 / 26 (3.85%)
    6 / 53 (11.32%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    1
    7
    2
    1
    2
    Fatigue
         subjects affected / exposed
    14 / 26 (53.85%)
    18 / 53 (33.96%)
    8 / 13 (61.54%)
    2 / 6 (33.33%)
    4 / 14 (28.57%)
         occurrences all number
    26
    38
    17
    4
    5
    Generalised Oedema
         subjects affected / exposed
    4 / 26 (15.38%)
    7 / 53 (13.21%)
    2 / 13 (15.38%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
         occurrences all number
    4
    9
    3
    2
    2
    Influenza Like Illness
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Infusion Site Extravasation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Localised Oedema
         subjects affected / exposed
    3 / 26 (11.54%)
    11 / 53 (20.75%)
    2 / 13 (15.38%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
         occurrences all number
    4
    24
    5
    3
    5
    Malaise
         subjects affected / exposed
    7 / 26 (26.92%)
    15 / 53 (28.30%)
    6 / 13 (46.15%)
    2 / 6 (33.33%)
    5 / 14 (35.71%)
         occurrences all number
    11
    20
    14
    4
    7
    Oedema Peripheral
         subjects affected / exposed
    8 / 26 (30.77%)
    19 / 53 (35.85%)
    4 / 13 (30.77%)
    3 / 6 (50.00%)
    5 / 14 (35.71%)
         occurrences all number
    10
    33
    6
    4
    9
    Pain
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 53 (5.66%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    3
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    4 / 26 (15.38%)
    6 / 53 (11.32%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    3 / 14 (21.43%)
         occurrences all number
    6
    7
    3
    0
    4
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 26 (7.69%)
    5 / 53 (9.43%)
    0 / 13 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    2
    6
    0
    1
    0
    Reproductive system and breast disorders
    Benign Prostatic Hyperplasia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Oedema Genital
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 53 (5.66%)
    0 / 13 (0.00%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    2
    3
    0
    1
    2
    Pelvic Pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    5
    0
    5
    0
    0
    Scrotal Swelling
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Arthropod Bite
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Contusion
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Head Injury
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Ligament Sprain
         subjects affected / exposed
    2 / 26 (7.69%)
    0 / 53 (0.00%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    Post-Traumatic Pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Procedural Nausea
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Road Traffic Accident
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Skin Abrasion
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Wound
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    4
    0
    0
    Wound Complication
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    2
    1
    0
    Investigations
    Blood Albumin Decreased
         subjects affected / exposed
    3 / 26 (11.54%)
    1 / 53 (1.89%)
    2 / 13 (15.38%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    5
    1
    4
    1
    1
    Blood Creatine Phosphokinase Increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Blood Folate Decreased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Blood Iron Decreased
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    1
    2
    0
    0
    Blood Phosphorus Increased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Haemoglobin Increased
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 53 (3.77%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    0
    0
    1
    Iron Binding Capacity Total Decreased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Iron Binding Capacity Unsaturated Decreased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    Platelet Count Increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    0 / 13 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Protein Total Decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Protein Total Increased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    4
    2
    0
    Protein Urine Present
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    0 / 13 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Reticulocyte Count Decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Reticulocyte Percentage Decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Serum Ferritin Decreased
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 53 (5.66%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Vitamin B12 Decreased
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Weight Decreased
         subjects affected / exposed
    7 / 26 (26.92%)
    4 / 53 (7.55%)
    3 / 13 (23.08%)
    3 / 6 (50.00%)
    2 / 14 (14.29%)
         occurrences all number
    9
    9
    5
    3
    5
    Weight Increased
         subjects affected / exposed
    0 / 26 (0.00%)
    11 / 53 (20.75%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    20
    0
    0
    1
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Ventricular Extrasystoles
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    8 / 26 (30.77%)
    8 / 53 (15.09%)
    3 / 13 (23.08%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    12
    14
    3
    1
    0
    Dyspnoea
         subjects affected / exposed
    9 / 26 (34.62%)
    13 / 53 (24.53%)
    4 / 13 (30.77%)
    0 / 6 (0.00%)
    3 / 14 (21.43%)
         occurrences all number
    12
    18
    6
    0
    4
    Epistaxis
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    2
    1
    0
    Nasal Inflammation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Oropharyngeal Pain
         subjects affected / exposed
    2 / 26 (7.69%)
    4 / 53 (7.55%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    5
    2
    0
    0
    Pleural Effusion
         subjects affected / exposed
    5 / 26 (19.23%)
    2 / 53 (3.77%)
    2 / 13 (15.38%)
    3 / 6 (50.00%)
    2 / 14 (14.29%)
         occurrences all number
    5
    2
    3
    3
    2
    Productive Cough
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 53 (3.77%)
    0 / 13 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    Wheezing
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 26 (19.23%)
    5 / 53 (9.43%)
    4 / 13 (30.77%)
    2 / 6 (33.33%)
    2 / 14 (14.29%)
         occurrences all number
    14
    6
    13
    3
    2
    Coagulopathy
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Leukocytosis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Leukopenia
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 53 (5.66%)
    1 / 13 (7.69%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
         occurrences all number
    3
    14
    2
    3
    3
    Lymph Node Pain
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Lymphopenia
         subjects affected / exposed
    3 / 26 (11.54%)
    0 / 53 (0.00%)
    2 / 13 (15.38%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    13
    0
    13
    1
    0
    Monocytosis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Neutropenia
         subjects affected / exposed
    3 / 26 (11.54%)
    7 / 53 (13.21%)
    2 / 13 (15.38%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
         occurrences all number
    8
    26
    6
    4
    5
    Neutrophilia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Splenomegaly
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 26 (7.69%)
    8 / 53 (15.09%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         occurrences all number
    6
    16
    6
    3
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 26 (7.69%)
    6 / 53 (11.32%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    4
    8
    0
    0
    0
    Headache
         subjects affected / exposed
    1 / 26 (3.85%)
    6 / 53 (11.32%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    1
    8
    0
    0
    2
    Peripheral Motor Neuropathy
         subjects affected / exposed
    4 / 26 (15.38%)
    6 / 53 (11.32%)
    2 / 13 (15.38%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
         occurrences all number
    6
    8
    4
    3
    1
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    7 / 26 (26.92%)
    13 / 53 (24.53%)
    5 / 13 (38.46%)
    3 / 6 (50.00%)
    3 / 14 (21.43%)
         occurrences all number
    12
    28
    11
    3
    3
    Somnolence
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    0
    0
    1
    Syncope
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Eye disorders
    Idiopathic Orbital Inflammation
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Noninfective Conjunctivitis
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    2
    2
    2
    1
    0
    Periorbital Oedema
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 53 (5.66%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    5
    2
    0
    3
    Vision Blurred
         subjects affected / exposed
    1 / 26 (3.85%)
    3 / 53 (5.66%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    3
    1
    0
    0
    Visual Acuity Reduced
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 53 (3.77%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    0
    0
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    0 / 13 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Vertigo
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 53 (3.77%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    4
    2
    0
    0
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    2
    1
    0
    Abdominal Distension
         subjects affected / exposed
    2 / 26 (7.69%)
    4 / 53 (7.55%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    3 / 14 (21.43%)
         occurrences all number
    2
    4
    1
    0
    3
    Abdominal Pain
         subjects affected / exposed
    2 / 26 (7.69%)
    8 / 53 (15.09%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    3
    10
    1
    0
    1
    Abdominal Pain Lower
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    Abdominal Pain Upper
         subjects affected / exposed
    2 / 26 (7.69%)
    5 / 53 (9.43%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    8
    6
    7
    1
    0
    Aphthous Ulcer
         subjects affected / exposed
    1 / 26 (3.85%)
    4 / 53 (7.55%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    5
    1
    0
    0
    Ascites
         subjects affected / exposed
    3 / 26 (11.54%)
    3 / 53 (5.66%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    5
    5
    6
    3
    2
    Constipation
         subjects affected / exposed
    2 / 26 (7.69%)
    6 / 53 (11.32%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    7
    1
    0
    1
    Diarrhoea
         subjects affected / exposed
    8 / 26 (30.77%)
    13 / 53 (24.53%)
    4 / 13 (30.77%)
    2 / 6 (33.33%)
    3 / 14 (21.43%)
         occurrences all number
    16
    18
    10
    2
    3
    Dyspepsia
         subjects affected / exposed
    4 / 26 (15.38%)
    2 / 53 (3.77%)
    3 / 13 (23.08%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    4
    2
    3
    0
    1
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    0 / 26 (0.00%)
    4 / 53 (7.55%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    6
    0
    0
    3
    Haemorrhoidal Haemorrhage
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Ileus Paralytic
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    7 / 26 (26.92%)
    5 / 53 (9.43%)
    3 / 13 (23.08%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    9
    10
    3
    1
    0
    Oesophagitis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Tongue Coated
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Tongue Ulceration
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    9
    1
    8
    0
    0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Vomiting
         subjects affected / exposed
    5 / 26 (19.23%)
    6 / 53 (11.32%)
    3 / 13 (23.08%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    7
    8
    4
    0
    2
    Renal and urinary disorders
    Azotaemia
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 53 (3.77%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    2
    4
    2
    1
    1
    Haematuria
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Pollakiuria
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    2
    1
    2
    1
    0
    Polyuria
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Proteinuria
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    1
    2
    0
    1
    Renal Impairment
         subjects affected / exposed
    2 / 26 (7.69%)
    4 / 53 (7.55%)
    2 / 13 (15.38%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    5
    9
    6
    1
    2
    Hepatobiliary disorders
    Hepatic Function Abnormal
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 53 (3.77%)
    3 / 13 (23.08%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    4
    5
    4
    0
    0
    Skin and subcutaneous tissue disorders
    Blister
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Dermatitis Acneiform
         subjects affected / exposed
    2 / 26 (7.69%)
    4 / 53 (7.55%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    8
    2
    0
    0
    Dry Skin
         subjects affected / exposed
    0 / 26 (0.00%)
    4 / 53 (7.55%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    Eczema
         subjects affected / exposed
    1 / 26 (3.85%)
    5 / 53 (9.43%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    6
    1
    0
    1
    Erythema
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 53 (3.77%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    3
    3
    3
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    7 / 26 (26.92%)
    10 / 53 (18.87%)
    5 / 13 (38.46%)
    2 / 6 (33.33%)
    2 / 14 (14.29%)
         occurrences all number
    9
    20
    9
    3
    4
    Night Sweats
         subjects affected / exposed
    4 / 26 (15.38%)
    9 / 53 (16.98%)
    4 / 13 (30.77%)
    1 / 6 (16.67%)
    4 / 14 (28.57%)
         occurrences all number
    6
    15
    7
    1
    5
    Pruritus
         subjects affected / exposed
    6 / 26 (23.08%)
    22 / 53 (41.51%)
    4 / 13 (30.77%)
    2 / 6 (33.33%)
    3 / 14 (21.43%)
         occurrences all number
    11
    47
    10
    2
    5
    Rash
         subjects affected / exposed
    1 / 26 (3.85%)
    7 / 53 (13.21%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    8
    0
    0
    0
    Rash Maculo-Papular
         subjects affected / exposed
    5 / 26 (19.23%)
    18 / 53 (33.96%)
    3 / 13 (23.08%)
    2 / 6 (33.33%)
    2 / 14 (14.29%)
         occurrences all number
    9
    37
    11
    5
    4
    Rash Pruritic
         subjects affected / exposed
    1 / 26 (3.85%)
    2 / 53 (3.77%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    3
    2
    3
    0
    0
    Skin Hyperpigmentation
         subjects affected / exposed
    0 / 26 (0.00%)
    5 / 53 (9.43%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    5
    0
    0
    1
    Skin Induration
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 53 (3.77%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    2
    2
    1
    1
    1
    Skin Ulcer
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 26 (19.23%)
    4 / 53 (7.55%)
    4 / 13 (30.77%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    6
    5
    5
    1
    2
    Arthritis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Back Pain
         subjects affected / exposed
    6 / 26 (23.08%)
    4 / 53 (7.55%)
    4 / 13 (30.77%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    8
    4
    7
    1
    1
    Chondropathy
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Joint Stiffness
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Muscle Spasms
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    Muscular Weakness
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 53 (5.66%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    3
    0
    0
    0
    Musculoskeletal Pain
         subjects affected / exposed
    2 / 26 (7.69%)
    3 / 53 (5.66%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    3
    3
    3
    0
    0
    Myalgia
         subjects affected / exposed
    3 / 26 (11.54%)
    2 / 53 (3.77%)
    3 / 13 (23.08%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    7
    2
    11
    4
    0
    Pain in Extremity
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    2 / 13 (15.38%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    2
    4
    3
    1
    0
    Synovitis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    7 / 26 (26.92%)
    9 / 53 (16.98%)
    4 / 13 (30.77%)
    3 / 6 (50.00%)
    4 / 14 (28.57%)
         occurrences all number
    7
    13
    6
    3
    6
    Enzyme Abnormality
         subjects affected / exposed
    4 / 26 (15.38%)
    1 / 53 (1.89%)
    4 / 13 (30.77%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    6
    2
    7
    1
    0
    Fluid Overload
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    2
    1
    0
    2
    Gout
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 53 (5.66%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    7
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    1
    1
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    3 / 53 (5.66%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    10
    0
    0
    1
    Hyperphosphataemia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    2 / 26 (7.69%)
    7 / 53 (13.21%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    15
    1
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    1 / 26 (3.85%)
    7 / 53 (13.21%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         occurrences all number
    3
    12
    6
    3
    5
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 26 (7.69%)
    2 / 53 (3.77%)
    1 / 13 (7.69%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
         occurrences all number
    2
    5
    2
    2
    1
    Hypocalcaemia
         subjects affected / exposed
    4 / 26 (15.38%)
    3 / 53 (5.66%)
    2 / 13 (15.38%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         occurrences all number
    4
    3
    2
    1
    3
    Hypocholesterolaemia
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    3
    1
    0
    2
    0
    Hypokalaemia
         subjects affected / exposed
    3 / 26 (11.54%)
    6 / 53 (11.32%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    5
    6
    1
    3
    1
    Hyponatraemia
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    1
    0
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    2
    2
    2
    0
    2
    Folliculitis
         subjects affected / exposed
    2 / 26 (7.69%)
    1 / 53 (1.89%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    2
    2
    0
    0
    Gastroenteritis
         subjects affected / exposed
    3 / 26 (11.54%)
    4 / 53 (7.55%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    3
    4
    1
    0
    2
    Herpes Virus Infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Herpes Zoster
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 53 (1.89%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 53 (3.77%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    6
    0
    0
    5
    Nasopharyngitis
         subjects affected / exposed
    1 / 26 (3.85%)
    9 / 53 (16.98%)
    1 / 13 (7.69%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    1
    10
    2
    1
    2
    Oral Candidiasis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Pharyngitis
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 26 (0.00%)
    2 / 53 (3.77%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    0
    0
    1
    Rash Pustular
         subjects affected / exposed
    2 / 26 (7.69%)
    4 / 53 (7.55%)
    2 / 13 (15.38%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    3
    5
    3
    0
    0
    Respiratory Tract Infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Skin Infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Tonsillitis
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 53 (1.89%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    0
    0
    1
    Upper Respiratory Tract Infection
         subjects affected / exposed
    6 / 26 (23.08%)
    20 / 53 (37.74%)
    4 / 13 (30.77%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    12
    31
    11
    1
    2
    Urinary Tract Infection
         subjects affected / exposed
    0 / 26 (0.00%)
    4 / 53 (7.55%)
    0 / 13 (0.00%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    0
    4
    0
    0
    0
    Viral Infection
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 53 (0.00%)
    1 / 13 (7.69%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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