Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2 clinical study of pomalidomide (CC-4047) monotherapy for children and young adults with recurrent or progressive primary brain tumors.

    Summary
    EudraCT number
    		 2016-002903-25
    Trial protocol
    		 ES   FR   GB   IT  
    Global end of trial date
    14 Sep 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Mar 2024
    First version publication date
    24 Mar 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CC-4047-BRN-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Oct 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Sep 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Establish the preliminary efficacy of pomalidomide in children and young adults with recurrent or progressive primary brain tumors within four distinct tumor types.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Sep 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 20
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    United States: 12
    Worldwide total number of subjects
    53
    EEA total number of subjects
    32
    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)
    26
    Adolescents (12-17 years)
    27
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study consisted of 4 groups, for each of the following primary brain tumor types: diffuse intrinsic pontine glioma (DIPG), ependymoma, high-grade glioma, and medulloblastoma.

    Pre-assignment
    Screening details
    		 In stage 1 approximately 9 participants were to be enrolled in parallel to each group. If two or more participants in a group achieved an objective response or long-term stable disease within the first 6 cycles of treatment (within the first 3 cycles for DIPG) an additional 11 participants were to be enrolled in that group.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Diffuse Intrinsic Pontine Glioma
    Arm description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    pomalidomide
    Investigational medicinal product code
    CC-4047
    Other name
    Pharmaceutical forms
    Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    2.6 mg/m²/day

    Arm title
    		 Ependymoma
    Arm description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    pomalidomide
    Investigational medicinal product code
    CC-4047
    Other name
    Pharmaceutical forms
    Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    2.6 mg/m²/day

    Arm title
    		 High-grade Glioma
    Arm description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    pomalidomide
    Investigational medicinal product code
    CC-4047
    Other name
    Pharmaceutical forms
    Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    2.6 mg/m²/day

    Arm title
    		 Medulloblastoma
    Arm description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    pomalidomide
    Investigational medicinal product code
    CC-4047
    Other name
    Pharmaceutical forms
    Capsule, Oral suspension
    Routes of administration
    Oral use
    Dosage and administration details
    2.6 mg/m²/day

    Number of subjects in period 1
    		Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Started
    11
    9
    23
    10
    Received Study Drug
    11
    9
    22
    10
    Completed
    0
    0
    1
    0
    Not completed
    11
    9
    22
    10
         Adverse event, serious fatal
    1
    -
    1
    1
         Adverse event, non-fatal
    -
    -
    2
    -
         Progressive Disease
    10
    9
    17
    8
         Withdrawal by Parent/Guardian
    -
    -
    2
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Diffuse Intrinsic Pontine Glioma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    Ependymoma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    High-grade Glioma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    Medulloblastoma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma Total
    Number of subjects
    		 11 9 23 10 53
    Age Categorical
    Units: participants
        ≥ 1 to < 6 years
    		 1 2 1 1 5
        ≥ 6 to < 12 years
    		 9 1 5 6 21
        ≥ 12 years
    		 1 6 17 3 27
    Age Continuous
    Units: years
        median (full range (min-max))
    		 7.0 (4 to 12) 12.0 (4 to 15) 14.0 (5 to 18) 10.0 (4 to 17) -
    Sex: Female, Male
    Units: participants
        Female
    		 4 4 8 3 19
        Male
    		 7 5 15 7 34
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 0 6 1 11
        Not Hispanic or Latino
    		 7 9 13 8 37
        Unknown or Not Reported
    		 0 0 4 1 5
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaskan Native
    		 0 0 0 0 0
        Asian
    		 1 0 2 0 3
        Black or African American
    		 0 0 2 0 2
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        White
    		 10 9 11 8 38
        Not Collected or Reported
    		 0 0 5 2 7
        Other
    		 0 0 3 0 3

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Diffuse Intrinsic Pontine Glioma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    Ependymoma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    High-grade Glioma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    Medulloblastoma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Primary: Percentage of Participants with an Objective Response and Long-term Stable Disease

    		 Close Top of page
    End point title
    		 Percentage of Participants with an Objective Response and Long-term Stable Disease [1]
    End point description
    The percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of < 50% or an increase of < 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
    End point type
    Primary
    End point timeframe
    6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only summary statistics planned for this endpoint.
    End point values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Number of subjects analysed
    9
    9
    19
    9
    Units: percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 33.6)
    11.1 (0.3 to 48.2)
    10.5 (1.3 to 33.1)
    0 (0.0 to 33.6)
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved an Objective Response (ORR)

    		 Close Top of page
    End point title
    		 Percentage of Participants who Achieved an Objective Response (ORR)
    End point description
    Objective response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) within the first 6 cycles of treatment (or within 3 cycles for participants in the DIPG group). Disease assessments were based on MRI and assessed by an independent central review. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
    End point type
    Secondary
    End point timeframe
    6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
    End point values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Number of subjects analysed
    9
    9
    19
    9
    Units: percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 33.6)
    0 (0.0 to 33.6)
    5.3 (0.1 to 26.0)
    0 (0.0 to 33.6)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Long-term Stable Disease

    		 Close Top of page
    End point title
    		 Percentage of Participants with Long-term Stable Disease
    End point description
    Long-term stable disease (SD) rate was defined as the percentage of participants who achieved SD maintained for ≥ 6 cycles (or > 3 cycles for DIPG), measured from the date of first dose of treatment. Disease assessments were based on MRI and assessed by an independent central review. SD: A decrease of < 50% or an increase of < 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
    End point type
    Secondary
    End point timeframe
    6 months (first 6 cycles) or 3 months (first 3 cycles) for participants in the DIPG group
    End point values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Number of subjects analysed
    9
    9
    19
    9
    Units: percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 33.6)
    11.1 (0.3 to 48.2)
    5.3 (0.1 to 26.0)
    0 (0.0 to 33.6)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Duration of Response (DoR)

    		 Close Top of page
    End point title
    		 Kaplan-Meier Estimate of Duration of Response (DoR)
    End point description
    DoR is defined as the time from the date of the first objective response (complete response [CR] or partial response [PR]) to disease progression. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at the time of start of new anticancer therapy, whichever occurred first. Progressive disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar cerebrospinal fluid (CSF) cytology were previously negative and became positive. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions compared to baseline, and/or the persistence of non-target lesions with no progression or decrease in size. -99999, 99999 = NA
    End point type
    Secondary
    End point timeframe
    From the first dose of pomalidomide to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 71 months)
    End point values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Number of subjects analysed
    1
    0 [2]
    1
    0 [3]
    Units: weeks
        median (confidence interval 95%)
    12.29 (-99999 to 99999)
    ( to )
    99999 (99999 to 99999)
    ( to )
    Notes
    [2] - 0 participants with CR or PR
    [3] - 0 participants with CR or PR
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Progression-Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Kaplan-Meier Estimate of Progression-Free Survival (PFS)
    End point description
    Progression-free survival was defined as the time from the date of first dose of pomalidomide until the date progressive disease (PD) was first observed or until the date of death due to any cause, whichever occurred first. Participants who did not have PD or had not died at the time of analysis were censored at the time of their last disease assessment or at the start of new anticancer therapy, whichever occurred first. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions taking as a reference the smallest disease measurement recorded since the start of protocol therapy (nadir), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or if spine MRI and/or lumbar CSF cytology were previously negative and became positive.
    End point type
    Secondary
    End point timeframe
    From the first dose of pomalidomide to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 71 months)
    End point values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Number of subjects analysed
    11
    9
    23
    10
    Units: weeks
        median (confidence interval 95%)
    11.43 (4.43 to 12.57)
    8.43 (5.57 to 16.14)
    7.86 (5.43 to 8.29)
    8.29 (7.29 to 18.00)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Kaplan-Meier Estimate of Overall Survival (OS)
    End point description
    Overall survival was defined as the time from the date of the first dose to the date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
    End point type
    Secondary
    End point timeframe
    From the first dose of pomalidomide to the date of death due to any cause (Up to 71 months)
    End point values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Number of subjects analysed
    11
    9
    23
    10
    Units: months
        median (confidence interval 95%)
    4.86 (1.02 to 10.91)
    12.02 (2.86 to 20.90)
    5.06 (2.04 to 16.66)
    11.60 (1.74 to 35.32)
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    		 Close Top of page
    End point title
    		 Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
    End point description
    Treatment-emergent adverse events were defined as any adverse events (AE) occurring from the first dose of pomalidomide until 28 days after the last dose. The severity of each AE was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 and according to the following scale: Grade 1: Mild (transient or mild discomfort; no limitation in activity or medical intervention required); Grade 2: Moderate (mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required); Grade 3: Severe (marked limitation in activity, assistance and medical intervention required, hospitalization possible); Grade 4: Life-threatening (extreme limitation in activity, significant assistance or medical intervention required, hospitalization or hospice care probable); Grade 5: Death. Drug-related AEs are those suspected by the Investigator as being related to administration of study drug.
    End point type
    Secondary
    End point timeframe
    From the first dose of pomalidomide until 28 days after the last dose (Up to approximately 72 months)
    End point values
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Number of subjects analysed
    11
    9
    22
    10
    Units: participants
        Any treatment-emergent adverse event (TEAE)
    11
    8
    21
    9
        TEAE related to study drug
    5
    7
    14
    8
        Serious TEAE
    9
    4
    14
    4
        Serious TEAE related to study drug
    1
    0
    6
    0
        Grade 3/4 TEAE
    8
    6
    14
    6
        Grade 3/4 TEAE related to study drug
    3
    2
    10
    4
        TEAE leading to death
    5
    1
    3
    1
        TEAE leading to dose reduction
    1
    0
    3
    0
        TEAE leading to dose interruption
    4
    3
    5
    2
        TEAE leading to study drug discontinuation
    2
    1
    2
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Participants were assessed for all-cause mortality from their first dose until their study completion (up to approximately 72 months). SAEs and other AEs were assessed from first dose until 28 days after last dose (up to approximately 72 months).
    Adverse event reporting additional description
    The number at Risk for All-cause mortality represents all enrolled participants, regardless of whether the participant received study treatment or not. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants who received at least 1 dose of pomalidomide.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Diffuse Intrinsic Pontine Glioma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    Ependymoma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    High-grade Glioma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Reporting group title
    Medulloblastoma
    Reporting group description
    		 Participants received 2.6 mg/m²/day oral pomalidomide on days 1 to 21 of each 28-day treatment cycle for up to 24 cycles or until disease progression, withdrawal of consent/assent, treatment became intolerable, or death, whichever occurred first.

    Serious adverse events
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 11 (81.82%)
    4 / 9 (44.44%)
    14 / 22 (63.64%)
    4 / 10 (40.00%)
         number of deaths (all causes)
    11
    6
    15
    9
         number of deaths resulting from adverse events
    5
    1
    3
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Hydrocephalus
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 9 (22.22%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    3 / 22 (13.64%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 9 (22.22%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyskinesia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ataxia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Monoplegia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neurological decompensation
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Dysmetria
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Gait disturbance
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    2 / 22 (9.09%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
    0 / 1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Respiratory syncytial virus bronchitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mastoiditis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anorectal infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Diffuse Intrinsic Pontine Glioma Ependymoma High-grade Glioma Medulloblastoma
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 11 (100.00%)
    8 / 9 (88.89%)
    20 / 22 (90.91%)
    9 / 10 (90.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Flushing
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Pallor
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Gait disturbance
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    1
    Fatigue
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    4 / 22 (18.18%)
    2 / 10 (20.00%)
         occurrences all number
    2
    1
    4
    2
    Asthenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    3 / 22 (13.64%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    3
    1
    General physical health deterioration
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    2
    1
    2
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Bronchostenosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Cough
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    3 / 22 (13.64%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    5
    0
    Tonsillar inflammation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypoxia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Pharyngeal erythema
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory failure
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Psychiatric disorders
    Personality change
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Confusional state
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    2 / 10 (20.00%)
         occurrences all number
    0
    0
    0
    2
    Anxiety
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    1
    1
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 9 (11.11%)
    4 / 22 (18.18%)
    2 / 10 (20.00%)
         occurrences all number
    1
    2
    4
    4
    Urine output decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Injury, poisoning and procedural complications
    Upper limb fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Ligament sprain
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Fall
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Contusion
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 11 (27.27%)
    4 / 9 (44.44%)
    5 / 22 (22.73%)
    3 / 10 (30.00%)
         occurrences all number
    5
    7
    14
    7
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    1
    1
    Depressed level of consciousness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Ataxia
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Aphasia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Hemiparesis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hydrocephalus
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Muscle spasticity
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Dizziness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    3 / 22 (13.64%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    6
    0
    VIth nerve disorder
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Tremor
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    1
    1
    Seizure
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Pyramidal tract syndrome
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    3 / 11 (27.27%)
    6 / 9 (66.67%)
    8 / 22 (36.36%)
    3 / 10 (30.00%)
         occurrences all number
    11
    10
    14
    3
    Febrile neutropenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Anaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    3 / 9 (33.33%)
    7 / 22 (31.82%)
    2 / 10 (20.00%)
         occurrences all number
    1
    4
    10
    2
    Lymphopenia
         subjects affected / exposed
    1 / 11 (9.09%)
    6 / 9 (66.67%)
    6 / 22 (27.27%)
    0 / 10 (0.00%)
         occurrences all number
    1
    10
    9
    0
    Neutropenia
         subjects affected / exposed
    3 / 11 (27.27%)
    7 / 9 (77.78%)
    9 / 22 (40.91%)
    4 / 10 (40.00%)
         occurrences all number
    15
    18
    29
    7
    Thrombocytopenia
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 9 (33.33%)
    8 / 22 (36.36%)
    3 / 10 (30.00%)
         occurrences all number
    0
    6
    12
    3
    Eye disorders
    Blindness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Conjunctival hyperaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Mydriasis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gastrointestinal disorders
    Salivary hypersecretion
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    1
    1
    Odynophagia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Nausea
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    4 / 22 (18.18%)
    1 / 10 (10.00%)
         occurrences all number
    4
    1
    7
    1
    Enteritis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Dysphagia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Dyspepsia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    5 / 22 (22.73%)
    2 / 10 (20.00%)
         occurrences all number
    0
    1
    9
    3
    Constipation
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    5 / 22 (22.73%)
    3 / 10 (30.00%)
         occurrences all number
    2
    1
    5
    3
    Abdominal pain
         subjects affected / exposed
    3 / 11 (27.27%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences all number
    3
    1
    6
    1
    Stomatitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 11 (18.18%)
    4 / 9 (44.44%)
    5 / 22 (22.73%)
    4 / 10 (40.00%)
         occurrences all number
    3
    5
    6
    5
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Skin and subcutaneous tissue disorders
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Eczema
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Dry skin
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 9 (22.22%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Dermatitis acneiform
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    1 / 10 (10.00%)
         occurrences all number
    1
    0
    2
    1
    Decubitus ulcer
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 9 (33.33%)
    2 / 22 (9.09%)
    2 / 10 (20.00%)
         occurrences all number
    0
    3
    2
    2
    Rash
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Pruritus
         subjects affected / exposed
    2 / 11 (18.18%)
    3 / 9 (33.33%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences all number
    2
    3
    1
    1
    Urticaria
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Rash pruritic
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Urinary hesitation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Urinary retention
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Urinary incontinence
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Muscular weakness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Muscle spasms
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    0
    1
    Neck pain
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    0 / 10 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Infections and infestations
    Molluscum contagiosum
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Laryngitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Eye infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Device related infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bronchitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    3
    1
    Otitis externa
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Parotitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    2 / 10 (20.00%)
         occurrences all number
    1
    1
    1
    2
    Rhinovirus infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rhinitis
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 9 (33.33%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    0
    3
    1
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 9 (0.00%)
    3 / 22 (13.64%)
    2 / 10 (20.00%)
         occurrences all number
    3
    0
    3
    2
    Hypercalcaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    0 / 22 (0.00%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    1 / 22 (4.55%)
    0 / 10 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    1 / 22 (4.55%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    1
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 9 (11.11%)
    2 / 22 (9.09%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    2
    1
    Hypokalaemia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 9 (11.11%)
    2 / 22 (9.09%)
    2 / 10 (20.00%)
         occurrences all number
    2
    1
    2
    4
    Hypomagnesaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    2
    Hyponatraemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    2 / 22 (9.09%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    2
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 9 (0.00%)
    0 / 22 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    0
    0
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Jun 2017
    Updated exploratory endpoints
    18 Aug 2017
    Updated inclusion and exclusion criteria
    20 Dec 2017
    Updated exclusion criteria

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon May 06 12:10:14 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA