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   43865   clinical trials with a EudraCT protocol, of which   7286   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 2/3 , Open-label, Single Arm, Multicentre Study to Assess Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Multiple Administrations of NI-0501, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, in Paediatric Patients with Primary Haemophagocytic Lymphohistiocytosis (HLH)

    Summary
    EudraCT number
    		 2012-003632-23
    Trial protocol
    		 GB   IT   AT   CZ   DE   ES   SE  
    Global end of trial date
    04 Jan 2019

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

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NI-0501-04
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01818492
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 US IND: 111015
    Sponsors
    Sponsor organisation name
    NovImmune SA
    Sponsor organisation address
    14 Chemin des Aulx, Plan-les-Ouates, Switzerland, CH-1228
    Public contact
    Carl Johan Treutiger, Sobi AG, carljohan.treutiger@sobi.com
    Scientific contact
    Carl Johan Treutiger, Sobi AG, carljohan.treutiger@sobi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002031-PIP01-16
    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
    31 Jan 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Jul 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jan 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    •To determine the safety and tolerability profile of multiple intravenous (IV) administrations of NI-0501. •To determine the efficacy and benefit/risk profile of NI-0501 in HLH patients. •To describe the PK profile of NI-0501 in HLH patients. •To determine the PD effects (levels of circulating Total IFNγ and biomarkers of its neutralization, namely CXCL9 and CXCL10) •To define an appropriate NI-0501 therapeutic dose regimen for HLH. •To determine other biomarkers, e.g. sCD25, IL-10 •To assess the immunogenicity of NI-0501.
    Protection of trial subjects
    Before screening, parents of each prospective patient were given a full explanation of the study. Once the Investigator was assured that the implications of participating in the study were understood, the parent(s) were asked to give consent for their child to participate in the study by signing the informed consent form.
    Background therapy
    		 In treatment-naïve patients, emapalumab was administered on a background of 10 mg/m2 of dexamethasone. In patients who received emapalumab as second line HLH treatment, dexamethasone was administered at a dose of at least 5 mg/m2, or at the dose administered prior to screening if higher. Lower dexamethasone doses were considered in the presence of signs and symptoms of glucocorticoid toxicity. Dexamethasone could be tapered during treatment with emapalumab, depending on the patient`s condition and according to the judgment of the Investigator.
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    28 Jul 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 1 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Italy: 16
    Country: Number of subjects enrolled
    United States: 23
    Country: Number of subjects enrolled
    United Kingdom: 2
    Worldwide total number of subjects
    45
    EEA total number of subjects
    22
    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)
    32
    Children (2-11 years)
    12
    Adolescents (12-17 years)
    1
    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
    		 Overall, 15 investigational sites in 5 countries (ie. UK, Germany, Italy, Spain and US) treated at least 1 patient in Study NI-0501-04.

    Pre-assignment
    Screening details
    		 Patients were screened within 1 week prior to the first administration of emapalumab (NI-0501). 66 patients were screened, and 45 were enrolled and treated.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 NI-0501
    Arm description
    		 All patients received emapalumab at a starting dose of 1 mg/kg every 3 days with possible escalation up to 10 mg/kg, for a minimum of 4 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    emapalumab
    Investigational medicinal product code
    NI-0501
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    The starting dose was 1 mg/kg every 3 days. Due to the expected target-mediated drug disposition (TMDD) effect and to the high interindividual variability of IFNγ concentrations in HLH patients, doses subsequent to the initial dose could be increased to 3 mg/kg and to 6 mg/kg, based on pre-specified clinical and laboratory criteria. Dose could be further increased up to 10 mg/kg, if required, upon approval by the DMC. If clinical and laboratory response criteria were no longer applicable, the dose of emapalumab could be decreased.

    Number of subjects in period 1
    		NI-0501
    Started
    45
    Completed
    35
    Not completed
    10
         Consent withdrawn by subject
    1
         Withdrawal criterion met in protocol
    4
         Adverse event, non-fatal
    2
         Death
    3

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    NI-0501
    Reporting group description
    		 All patients received emapalumab at a starting dose of 1 mg/kg every 3 days with possible escalation up to 10 mg/kg, for a minimum of 4 weeks.

    Reporting group values
    		 NI-0501 Total
    Number of subjects
    		 45 45
    Age categorical
    In the All Treated population, the median age at entry into the study was 1.0 year, with a range of 0.1 (1 month) to 13.0 years.
    Units: Subjects
        Infants and toddlers (28 days-23 months)
    		 32 32
        Children (2-11 years)
    		 12 12
        Adolescents (12-17 years)
    		 1 1
    Gender categorical
    The study population comprised patients of both genders
    Units: Subjects
        Female
    		 23 23
        Male
    		 22 22
    Race
    Units: Subjects
        White
    		 30 30
        Asian
    		 7 7
        African Descent
    		 3 3
        Mixed/multi-racial
    		 0 0
        Other
    		 5 5
    Country of Origin
    Units: Subjects
        US
    		 11 11
        Italy
    		 6 6
        Others
    		 19 19
        Missing
    		 9 9
    Subject analysis sets

    Subject analysis set title
    Primary analysis set: All Treated
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Primary analysis set: All Treated (all patients who received any part of an emapalumab infusion, data collected by cut-off: 20 July 2017)

    Subject analysis set title
    Primary analysis set: Second Line
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Primary analysis set: Second Line (27 patients who had previously received conventional HLH therapy before enrollment, data collected by cut-off: 20 July 2017)

    Subject analysis set title
    Baseline
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Baseline for comparison of primary endpoint

    Subject analysis set title
    Follow-on analysis set: Second Line
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Follow-on analysis set: Second Line (34 patients who had previously received conventional HLH therapy before enrollment, totality of the data collected in the NI-0501-04 study)

    Subject analysis set title
    Follow-on analysis set: All Treated
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Follow-on analysis set: All Treated (45 patients who received any part of an emapalumab infusion, totality of the data collected in the NI-0501-04)

    Subject analysis sets values
    		 Primary analysis set: All Treated Primary analysis set: Second Line Baseline Follow-on analysis set: Second Line Follow-on analysis set: All Treated
    Number of subjects
    34
    27
    45
    34
    45
    Age categorical
    In the All Treated population, the median age at entry into the study was 1.0 year, with a range of 0.1 (1 month) to 13.0 years.
    Units: Subjects
        Infants and toddlers (28 days-23 months)
    21
    15
    32
    21
    32
        Children (2-11 years)
    12
    11
    12
    12
    12
        Adolescents (12-17 years)
    1
    1
    1
    1
    1
    Age continuous
    Units:
         (full range (min-max))
    Gender categorical
    The study population comprised patients of both genders
    Units: Subjects
        Female
    18
    16
    23
    19
    23
        Male
    16
    11
    22
    15
    22
    Race
    Units: Subjects
        White
    22
    17
    30
    23
    30
        Asian
    5
    3
    7
    3
    7
        African Descent
    3
    3
    3
    3
    3
        Mixed/multi-racial
    0
    0
    0
    0
    0
        Other
    4
    4
    5
    5
    5
    Country of Origin
    Units: Subjects
        US
    8
    7
    11
    8
    11
        Italy
    4
    3
    6
    4
    6
        Others
    16
    12
    19
    14
    19
        Missing
    6
    5
    9
    8
    9

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    NI-0501
    Reporting group description
    		 All patients received emapalumab at a starting dose of 1 mg/kg every 3 days with possible escalation up to 10 mg/kg, for a minimum of 4 weeks.

    Subject analysis set title
    Primary analysis set: All Treated
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Primary analysis set: All Treated (all patients who received any part of an emapalumab infusion, data collected by cut-off: 20 July 2017)

    Subject analysis set title
    Primary analysis set: Second Line
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Primary analysis set: Second Line (27 patients who had previously received conventional HLH therapy before enrollment, data collected by cut-off: 20 July 2017)

    Subject analysis set title
    Baseline
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Baseline for comparison of primary endpoint

    Subject analysis set title
    Follow-on analysis set: Second Line
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Follow-on analysis set: Second Line (34 patients who had previously received conventional HLH therapy before enrollment, totality of the data collected in the NI-0501-04 study)

    Subject analysis set title
    Follow-on analysis set: All Treated
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Follow-on analysis set: All Treated (45 patients who received any part of an emapalumab infusion, totality of the data collected in the NI-0501-04)

    Primary: Overall Response

    		 Close Top of page
    End point title
    		 Overall Response
    End point description
    Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm. CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin <2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen >150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25. PR: at least 3 HLH clinical and laboratory criteria (including CNS abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (>50% change from baseline) of at least 3 HLH clinical and laboratory criteria (including CNS involvement).
    End point type
    Primary
    End point timeframe
    End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks)
    End point values
    		 Primary analysis set: All Treated Primary analysis set: Second Line Baseline Follow-on analysis set: Second Line Follow-on analysis set: All Treated
    Number of subjects analysed
    34
    27
    45
    34
    45
    Units: Overall Response Rate
        number (confidence interval 95%)
    0.65 (0.47 to 0.80)
    0.63 (0.42 to 0.81)
    0 (0 to 0)
    0.59 (0.41 to 0.75)
    0.60 (0.44 to 0.74)
    Statistical analysis title
    		 Exact binomial test
    Statistical analysis description
    The primary efficacy endpoint was analyzed with an exact binomial test to evaluate the null hypothesis that the Overall Response Rate was at most 40%. This test was performed at the one sided 0.025 significance level. Due to the inability of presenting the statistical analysis for single arm studies correctly, it is described here as a comparison to baseline.
    Comparison groups
    Primary analysis set: Second Line v Baseline
    Number of subjects included in analysis
    72
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.0134 [2]
    Method
    		 Exact Bionmial
    Confidence interval
    Notes
    [1] - Pre-specified null hypothesis that ORR is at most 40%.
    [2] - This test was undertaken at the one-sided 0.025 significance level.
    Statistical analysis title
    		 Exact binomial test
    Statistical analysis description
    Due to the inability of presenting the statistical analysis for single arm studies correctly, it is described here as a comparison to baseline.
    Comparison groups
    Primary analysis set: All Treated v Baseline
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.0031 [4]
    Method
    		 Exact binomial
    Confidence interval
    Notes
    [3] - Pre-specified null hypothesis that ORR is at most 40%
    [4] - This test was undertaken at the one-sided 0.025 significance level.
    Statistical analysis title
    		 Exact binomial test
    Statistical analysis description
    Due to the inability of presenting the statistical analysis for single arm studies correctly, it is described here as a comparison to baseline.
    Comparison groups
    Follow-on analysis set: Second Line v Baseline
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.0205 [6]
    Method
    		 Exact binomial
    Confidence interval
    Notes
    [5] - Pre-specified null hypothesis that ORR is at most 40%
    [6] - This test was undertaken at the one-sided 0.025 significance level.
    Statistical analysis title
    		 Exact binomial test
    Statistical analysis description
    Due to the inability of presenting the statistical analysis for single arm studies correctly, it is described here as a comparison to baseline.
    Comparison groups
    Follow-on analysis set: All Treated v Baseline
    Number of subjects included in analysis
    90
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.0053 [8]
    Method
    		 Exact binomial
    Confidence interval
    Notes
    [7] - Pre-specified null hypothesis that ORR is at most 40%.
    [8] - This test was undertaken at the one-sided 0.025 significance level.

    Secondary: Time to Overall Response

    		 Close Top of page
    End point title
    		 Time to Overall Response
    End point description
    Time from the date of the first dose of emapalumab to first achievement of response (at least HLH improvement)
    End point type
    Secondary
    End point timeframe
    Any time during the study
    End point values
    		 Follow-on analysis set: All Treated
    Number of subjects analysed
    45
    Units: Days
        median (confidence interval 95%)
    7.0 (6.0 to 9.0)
    No statistical analyses for this end point

    Secondary: Durability of First Response

    		 Close Top of page
    End point title
    		 Durability of First Response
    End point description
    Maintenance of response achieved any time during the study
    End point type
    Secondary
    End point timeframe
    Any time during the study
    End point values
    		 Follow-on analysis set: All Treated
    Number of subjects analysed
    45
    Units: At least 1 response (number)
    39
    No statistical analyses for this end point

    Secondary: Glucocortoid Tapering

    		 Close Top of page
    End point title
    		 Glucocortoid Tapering
    End point description
    Number of patients able to reduce glucocorticoids by 50% or more of baseline dose at EOT 04
    End point type
    Secondary
    End point timeframe
    Any time during the study up to EOT 04
    End point values
    		 Follow-on analysis set: All Treated
    Number of subjects analysed
    45
    Units: Percentage of patients
    number (not applicable)
        Reduction ≥50%
    46.7
        Reduction ≥30%-<50%
    11.1
    No statistical analyses for this end point

    Secondary: Survival Pre-HSCT

    		 Close Top of page
    End point title
    		 Survival Pre-HSCT
    End point description
    Time from the date of first dose to the date of death, expressed in Kaplan-Meier survival probability estimates. Patients who receive HSCT will be censored at that date; patients who did not receive HSCT will be censored at last date of contact. Where applicable, data were collected in both NI-0501-04 and long-term follow-up study NI-0501-05.
    End point type
    Secondary
    End point timeframe
    End of the study and beyond
    End point values
    		 Follow-on analysis set: All Treated
    Number of subjects analysed
    35
    Units: Kaplan-Meier survival probability
    number (confidence interval 95%)
        Month 3
    0.83 (0.669 to 0.915)
        Month 6
    0.73 (0.524 to 0.859)
    No statistical analyses for this end point

    Secondary: Overall Survival

    		 Close Top of page
    End point title
    		 Overall Survival
    End point description
    Time from the date of first dose to the date of death, expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at last assessment date in either the NI-0501-04 or NI-0501-05 study.
    End point type
    Secondary
    End point timeframe
    End of the study and beyond
    End point values
    		 Follow-on analysis set: All Treated
    Number of subjects analysed
    45
    Units: Kaplan-Meier survival probability
    number (confidence interval 95%)
        Month 6
    0.68 (0.523 to 0.798)
        Month 12
    0.66 (0.493 to 0.776)
    No statistical analyses for this end point

    Secondary: Survival Post-HSCT

    		 Close Top of page
    End point title
    		 Survival Post-HSCT
    End point description
    Time from the date of first dose to the date of death, expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at last assessment date in either the NI-0501-04 or NI-0501-05 study. Patients who do not proceed to HSCT will be excluded from this analysis.
    End point type
    Secondary
    End point timeframe
    End of the study and beyond
    End point values
    		 Follow-on analysis set: All Treated
    Number of subjects analysed
    24
    Units: Kaplan-Meier survival probability
    number (confidence interval 95%)
        Month 6
    0.82 (0.621 to 0.921)
        Month 12
    0.82 (0.621 to 0.921)
    No statistical analyses for this end point

    Secondary: Cumulative Duration of Response

    		 Close Top of page
    End point title
    		 Cumulative Duration of Response
    End point description
    Percent of treatment time in response from the first achievement of an Overall Response until HSCT conditioning, or End of Treatment 04/05 (if the patient did not have HSCT performed) Where applicable, data were collected in both NI-0501-04 and long-term follow-up study NI-0501-05.
    End point type
    Secondary
    End point timeframe
    Up to start of HSCT conditioning, whenever HSCT conditioning is scheduled (at least 4 weeks after treatment start), or End of Treatment 04/05 (if the patient did not have HSCT performed)
    End point values
    		 Follow-on analysis set: All Treated
    Number of subjects analysed
    45
    Units: Percentage of treatment time
        number (confidence interval 95%)
    78.6 (33.0 to 91.9)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Any adverse event occurring after study start (i.e. signing of the informed consent) until the end of emapalumab treatment
    Adverse event reporting additional description
    All patients who have received any part of an infusion of the study drug
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Pre-conditioning
    Reporting group description
    		 All patients before start of conditioning

    Reporting group title
    Post-conditioning
    Reporting group description
    		 All patients after start of conditioning

    Serious adverse events
    		 Pre-conditioning Post-conditioning
    Total subjects affected by serious adverse events
         subjects affected / exposed
    28 / 45 (62.22%)
    20 / 30 (66.67%)
         number of deaths (all causes)
    9
    5
         number of deaths resulting from adverse events
    9
    5
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Condition aggravated
         subjects affected / exposed
    7 / 45 (15.56%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 8
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    4 / 45 (8.89%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 3
    0 / 2
    Pyrexia
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 30 (10.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Acute graft versus host disease in intestine
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Engraftment syndrome
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Aspiration
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary artery thrombosis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemothorax
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatine increased
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Blood stem cell transplant failure
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Engraft failure
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular dysfunction
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral disorder
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological decompensation
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural hygroma
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphocytosis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Eye movement disorder
         subjects affected / exposed
    1 / 45 (2.22%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumatosis intestinalis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis perforated
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis norovirus
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Histoplasmosis disseminated
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Necrotising fasciitis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pseudomonal
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    3 / 45 (6.67%)
    3 / 30 (10.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Sinusitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 45 (4.44%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gianotti-Crosti syndrome
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia cytomegaloviral
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 45 (0.00%)
    1 / 30 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Pre-conditioning Post-conditioning
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    43 / 45 (95.56%)
    30 / 30 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiocentric lymphoma
         subjects affected / exposed
    1 / 45 (2.22%)
    0 / 30 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    19 / 45 (42.22%)
    11 / 30 (36.67%)
         occurrences all number
    22
    12
    Hypotension
         subjects affected / exposed
    5 / 45 (11.11%)
    3 / 30 (10.00%)
         occurrences all number
    6
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Condition aggravated
         subjects affected / exposed
    23 / 45 (51.11%)
    3 / 30 (10.00%)
         occurrences all number
    29
    3
    Mucosal inflammation
         subjects affected / exposed
    1 / 45 (2.22%)
    8 / 30 (26.67%)
         occurrences all number
    1
    8
    Oedema
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    2
    3
    Oedema peripheral
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    5
    0
    Pain
         subjects affected / exposed
    6 / 45 (13.33%)
    3 / 30 (10.00%)
         occurrences all number
    6
    4
    Pyrexia
         subjects affected / exposed
    15 / 45 (33.33%)
    15 / 30 (50.00%)
         occurrences all number
    25
    25
    Immune system disorders
    Graft versus host disease
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Graft versus host disease in liver
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Graft versus host disease in skin
         subjects affected / exposed
    0 / 45 (0.00%)
    5 / 30 (16.67%)
         occurrences all number
    0
    5
    Respiratory, thoracic and mediastinal disorders
    Atelectasis
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Cough
         subjects affected / exposed
    4 / 45 (8.89%)
    2 / 30 (6.67%)
         occurrences all number
    4
    2
    Dyspnoea
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Epistaxis
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    Hypoxia
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Respiratory failure
         subjects affected / exposed
    5 / 45 (11.11%)
    1 / 30 (3.33%)
         occurrences all number
    5
    1
    Tachypnoea
         subjects affected / exposed
    7 / 45 (15.56%)
    3 / 30 (10.00%)
         occurrences all number
    11
    3
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 30 (6.67%)
         occurrences all number
    3
    2
    Irritability
         subjects affected / exposed
    5 / 45 (11.11%)
    3 / 30 (10.00%)
         occurrences all number
    7
    3
    Investigations
    Blood immunoglobulin G decreased
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    1
    6
    Human rhinovirus test positive
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    Polyomavirus test positive
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    4
    Adenovirus test positive
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    3
    Hypomagnesaemia
         subjects affected / exposed
    3 / 45 (6.67%)
    4 / 30 (13.33%)
         occurrences all number
    3
    5
    Transaminases increased
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Skin abrasion
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 30 (0.00%)
         occurrences all number
    4
    0
    Pericardial effusion
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Tachycardia
         subjects affected / exposed
    8 / 45 (17.78%)
    3 / 30 (10.00%)
         occurrences all number
    11
    3
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Lymphocytosis
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 30 (0.00%)
         occurrences all number
    5
    0
    Thrombotic microangiopathy
         subjects affected / exposed
    2 / 45 (4.44%)
    5 / 30 (16.67%)
         occurrences all number
    2
    5
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    3 / 45 (6.67%)
    1 / 30 (3.33%)
         occurrences all number
    4
    1
    Abdominal pain
         subjects affected / exposed
    5 / 45 (11.11%)
    5 / 30 (16.67%)
         occurrences all number
    7
    5
    Constipation
         subjects affected / exposed
    6 / 45 (13.33%)
    0 / 30 (0.00%)
         occurrences all number
    7
    0
    Diarrhoea
         subjects affected / exposed
    8 / 45 (17.78%)
    6 / 30 (20.00%)
         occurrences all number
    11
    11
    Nausea
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    4
    Stomatitis
         subjects affected / exposed
    1 / 45 (2.22%)
    6 / 30 (20.00%)
         occurrences all number
    1
    6
    Vomiting
         subjects affected / exposed
    5 / 45 (11.11%)
    7 / 30 (23.33%)
         occurrences all number
    12
    9
    Skin and subcutaneous tissue disorders
    Drug eruption
         subjects affected / exposed
    4 / 45 (8.89%)
    0 / 30 (0.00%)
         occurrences all number
    5
    0
    Erythema
         subjects affected / exposed
    4 / 45 (8.89%)
    4 / 30 (13.33%)
         occurrences all number
    5
    6
    Hyperhidrosis
         subjects affected / exposed
    4 / 45 (8.89%)
    1 / 30 (3.33%)
         occurrences all number
    6
    1
    Pruritus
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Rash
         subjects affected / exposed
    7 / 45 (15.56%)
    6 / 30 (20.00%)
         occurrences all number
    14
    9
    Rash erythematous
         subjects affected / exposed
    2 / 45 (4.44%)
    3 / 30 (10.00%)
         occurrences all number
    2
    3
    Rash maculo-papular
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Skin disorder
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Rash macular
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 45 (0.00%)
    3 / 30 (10.00%)
         occurrences all number
    0
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Back pain
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Infections and infestations
    BK virus infection
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2
    Clostridium difficile infection
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 30 (6.67%)
         occurrences all number
    3
    2
    Cytomegalovirus infection
         subjects affected / exposed
    4 / 45 (8.89%)
    5 / 30 (16.67%)
         occurrences all number
    5
    7
    Otitis externa
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    1
    2
    Rhinitis
         subjects affected / exposed
    1 / 45 (2.22%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Staphylococcal bacteraemia
         subjects affected / exposed
    3 / 45 (6.67%)
    3 / 30 (10.00%)
         occurrences all number
    4
    4
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 45 (6.67%)
    0 / 30 (0.00%)
         occurrences all number
    3
    0
    Urinary tract infection
         subjects affected / exposed
    2 / 45 (4.44%)
    0 / 30 (0.00%)
         occurrences all number
    2
    0
    Metabolism and nutrition disorders
    Fluid overload
         subjects affected / exposed
    2 / 45 (4.44%)
    4 / 30 (13.33%)
         occurrences all number
    2
    5
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 45 (4.44%)
    3 / 30 (10.00%)
         occurrences all number
    2
    3
    Hypocalcaemia
         subjects affected / exposed
    1 / 45 (2.22%)
    3 / 30 (10.00%)
         occurrences all number
    2
    4
    Hypokalaemia
         subjects affected / exposed
    7 / 45 (15.56%)
    4 / 30 (13.33%)
         occurrences all number
    10
    7
    Hyponatraemia
         subjects affected / exposed
    2 / 45 (4.44%)
    2 / 30 (6.67%)
         occurrences all number
    2
    2
    Hypophosphataemia
         subjects affected / exposed
    3 / 45 (6.67%)
    2 / 30 (6.67%)
         occurrences all number
    3
    2
    Dehydration
         subjects affected / exposed
    0 / 45 (0.00%)
    2 / 30 (6.67%)
         occurrences all number
    0
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Jan 2013
    Protocol NI-0501-04 EU version 2.1 - Addition of advice on contraception, and exclusion of pregnancy and lactation - Clarification on the dose escalation process - Revision of the IMP preparation form - Clarification of the 4-week follow-up period after treatment discontinuation
    13 Dec 2013
    EU version 3.0 - Amendment of the protocol number to reflect the introduction of the US twin protocol - Implementation of a combined analysis of the data generated by the EU and US protocol - Clarifications of a few protocol sections (eg, Inclusion/Exclusion Criteria, study design, study outline and stopping rules) and introducing few additional clinical assessments (non-invasive), as well as PK and laboratory measurements, aimed at facilitating the analysis of the data
    07 May 2014
    US version 3.0 16 April 2014 EU version 4.0 07 May 2014 - Broadening of the patient population eligible to receive NI-0501 in the study: In addition to primary HLH patients reactivating after having achieved Partial Response following conventional therapy, the protocol allowed the inclusion of primary HLH patients who received conventional therapy and: 1. Worsened or showed no further improvement for at least 4 weeks from initiation of treatment after achieving at least Partial or Incomplete Response 2. Showed no response after at least 2 weeks from initiation of conventional therapy or worsening of the disease 3. Showed intolerance to conventional treatment of HLH
    15 Dec 2014
    US version 4.0 17 November 2014 EU version 5.0 15 December 2014 - Broadening of the target patient population to include patients naïve to HLH treatment - Revision of the title of the study to reflect the changes made to the Study Population and the Inclusion Criteria - Revision of the dose regimen, the dose determination criteria, and the background therapy requirements
    26 Feb 2016
    EU version 6.0 26 February 2016 US Version 5.1 24 March 2016 - Prolongation of the study to continue as Phase 2/3, with determination of sample size for the pivotal cohort (defined as patients who receive NI-0501 in second line) - Definition of primary and secondary efficacy endpoints, consistently with the amended phase of the study consistently with the amended phase of the study - Revision of the dosing regimen and implementation of a standardized approach to dose increase. Clinical criteria were indicated to guide the dose increase by the Investigator. Dose increase was allowed at any time during the course of the study - Possibility to add other HLH treatments, primarily etoposide, if pre-defined criteria were met - Update to the stopping rules to reflect the experience gathered with the drug and the amended phase of the study

    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 Apr 29 02:17:34 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA