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    Clinical Trial Results:
    A randomized, open-label, phase I/II open platform study evaluating safety and efficacy of novel ruxolitinib combinations in myelofibrosis patients

    Summary
    EudraCT number
    		 2019-000373-23
    Trial protocol
    		 DK   DE   BE   NL   IT   ES   HU   AT   RO  
    Global end of trial date
    28 Aug 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Aug 2025
    First version publication date
    06 Aug 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CINC424H12201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04097821
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Aug 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Aug 2024
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective was to characterize the safety, tolerability, and recommended Phase 2 dose (RP2D) of each combination partner used with ruxolitinib (Part 1 core). Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    26 Sep 2019
    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
    Australia: 9
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    Hungary: 2
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Russian Federation: 2
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Sweden: 1
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    Türkiye: 1
    Country: Number of subjects enrolled
    United Kingdom: 1
    Worldwide total number of subjects
    45
    EEA total number of subjects
    28
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    18
    From 65 to 84 years
    26
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 All inclusion and exclusion criteria were checked at screening.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part 1: Ruxolitinib + Siremadlin 20 mg
    Arm description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib
    Arm type
    		 Experimental

    Investigational medicinal product name
    Siremadlin
    Investigational medicinal product code
    Other name
    HDM201
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg, 20 mg, or 40 mg capsules for oral use

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Arm title
    		 Part 1: Ruxolitinib + Siremadlin 30 mg
    Arm description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib
    Arm type
    		 Experimental

    Investigational medicinal product name
    Siremadlin
    Investigational medicinal product code
    Other name
    HDM201
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg, 20 mg, or 40 mg capsules for oral use

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Arm title
    		 Part 1: Ruxolitinib + Siremadlin 40 mg
    Arm description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib
    Arm type
    		 Experimental

    Investigational medicinal product name
    Siremadlin
    Investigational medicinal product code
    Other name
    HDM201
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    10 mg, 20 mg, or 40 mg capsules for oral use

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Arm title
    		 Part 1: Ruxolitinib + Rineterkib 200 mg
    Arm description
    		 Dose escalation of rineterkib added to existing stable dose of ruxolitinib
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rineterkib
    Investigational medicinal product code
    Other name
    LTT462
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 mg capsule for oral use

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Arm title
    		 Part 1: Ruxolitinib + Crizanlizumab
    Arm description
    		 Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib
    Arm type
    		 Experimental

    Investigational medicinal product name
    Crizanlizumab
    Investigational medicinal product code
    Other name
    SEG101
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg/10 mL concentrate for infusion for intravenous use

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Arm title
    		 Part 1: Ruxolitinib + Sabatolimab
    Arm description
    		 Safety run-in of sabatolimab added to existing stable dose of ruxolitinib
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sabatolimab
    Investigational medicinal product code
    Other name
    MBG453
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg/mL or 400 mg/4 mL concentrate for infusion for intravenous use

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Arm title
    		 Part 1: Ruxolitinib + NIS793
    Arm description
    		 Safety run-in of NIS793 added to existing stable dose of ruxolitinib
    Arm type
    		 Experimental

    Investigational medicinal product name
    NIS793
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    700 mg/7 mL concentrate for infusion for intravenous use

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Arm title
    		 Part 2: Ruxolitinib
    Arm description
    		 Existing stable dose of ruxolitinib as control for Part 2
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Ruxolitinib
    Investigational medicinal product code
    Other name
    INC424, Jakavi
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    5 mg tablets for oral use

    Number of subjects in period 1
    		Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793 Part 2: Ruxolitinib
    Started
    7
    10
    6
    9
    6
    2
    4
    1
    Completed
    5
    8
    2
    5
    4
    0
    3
    0
    Not completed
    2
    2
    4
    4
    2
    2
    1
    1
         Adverse event, serious fatal
    -
    -
    3
    1
    -
    -
    -
    -
         Physician decision
    1
    1
    -
    -
    -
    -
    -
    -
         Subject Decision
    -
    -
    -
    1
    2
    2
    -
    1
         Adverse event, non-fatal
    -
    -
    -
    1
    -
    -
    -
    -
         Treated in Extension Phase
    1
    1
    1
    1
    -
    -
    -
    -
         New Therapy For Study Indication
    -
    -
    -
    -
    -
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 20 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 30 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 40 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Rineterkib 200 mg
    Reporting group description
    		 Dose escalation of rineterkib added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Crizanlizumab
    Reporting group description
    		 Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Sabatolimab
    Reporting group description
    		 Safety run-in of sabatolimab added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + NIS793
    Reporting group description
    		 Safety run-in of NIS793 added to existing stable dose of ruxolitinib

    Reporting group title
    Part 2: Ruxolitinib
    Reporting group description
    		 Existing stable dose of ruxolitinib as control for Part 2

    Reporting group values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793 Part 2: Ruxolitinib Total
    Number of subjects
    		 7 10 6 9 6 2 4 1 45
    Age Categorical
    Units: participants
        <65
    		 1 5 1 4 4 1 1 1 18
        >=65
    		 6 5 5 5 2 1 3 0 27
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 70.6 ( 6.5 ) 62.3 ( 10.7 ) 74.3 ( 9.9 ) 67.3 ( 7.8 ) 65.0 ( 8.1 ) 62.5 ( 12.0 ) 70.8 ( 7.3 ) 58.0 ( 0 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 2 6 0 2 1 0 1 1 13
        Male
    		 5 4 6 7 5 2 3 0 32
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 7 10 6 8 5 2 4 1 43
        Unknown
    		 0 0 0 1 1 0 0 0 2

    End points

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    End points reporting groups
    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 20 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 30 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 40 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Rineterkib 200 mg
    Reporting group description
    		 Dose escalation of rineterkib added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Crizanlizumab
    Reporting group description
    		 Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Sabatolimab
    Reporting group description
    		 Safety run-in of sabatolimab added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + NIS793
    Reporting group description
    		 Safety run-in of NIS793 added to existing stable dose of ruxolitinib

    Reporting group title
    Part 2: Ruxolitinib
    Reporting group description
    		 Existing stable dose of ruxolitinib as control for Part 2

    Subject analysis set title
    Part 1:Ruxolitinib + Siremadlin 20 mg (AUClast for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1:Ruxolitinib + Siremadlin 30 mg (AUClast for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1:Ruxolitinib + Siremadlin 40 mg (AUClast for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1:Ruxolitinib+ Rineterkib 200 mg (AUClast for Rineterkib)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of rineterkib added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1:Ruxolitinib + Crizanlizumab (AUClast for Crizanlizumab)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Sabatolimab (AUClast for Sabatolimab)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of sabatolimab added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + NIS793 (AUClast for NIS793)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of NIS793 added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Siremadlin 20 mg (Cmax for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Siremadlin 30 mg (Cmax for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Siremadlin 40 mg (Cmax for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Rineterkib 200 mg (Cmax for Rineterkib)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of rineterkib added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Crizanlizumab (Cmax for Crizanlizumab)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Sabatolimab (Cmax for Sabatolimab)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of sabatolimab added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + NIS793 (Cmax for NIS793)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of NIS793 added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Siremadlin 20 mg (Tmax for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Siremadlin 30 mg (Tmax for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Siremadlin 40 mg (Tmax for Siremadlin)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Rineterkib 200 mg (Tmax for Rineterkib)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Dose escalation of rineterkib added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Crizanlizumab (Tmax for Crizanlizumab)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + Sabatolimab (Tmax for Sabatolimab)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of sabatolimab added to existing stable dose of ruxolitinib

    Subject analysis set title
    Part 1: Ruxolitinib + NIS793 (Tmax for NIS793)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Safety run-in of NIS793 added to existing stable dose of ruxolitinib

    Primary: Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1

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    End point title
    		 Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1 [1] [2]
    End point description
    Incidence and severity of dose limiting toxicities within the first 2 cycles (6 or 8 weeks) in Part 1 of the study. DLTs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria Version 5.0. Grade 0 was assigned for all non-missing values not graded as 1 or higher. Higher grade indicated more severity. Grade 5 was not used.
    End point type
    Primary
    End point timeframe
    Baseline to the end of Cycle 2 (6 or 8 weeks)
    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: No statistical analysis was planned for this primary outcome.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    6
    7
    5
    9
    5
    2
    0 [3]
    Units: participants
        Grade 3
    0
    0
    1
    1
    0
    0
        Grade 4
    0
    1
    1
    0
    0
    0
    Notes
    [3] - Number analyzed is the number of participants with available data.
    No statistical analyses for this end point

    Primary: Response Rate at the End of Cycle 6 or Cycle 8 in Part 1

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    End point title
    		 Response Rate at the End of Cycle 6 or Cycle 8 in Part 1 [4] [5]
    End point description
    Composite of anemia improvement (hemoglobin level) and no spleen volume progression and no symptom worsening in Part 2 and Part 3 of the study. For a subject to be considered a responder, all three components of the composite had to be fulfilled.
    End point type
    Primary
    End point timeframe
    Baseline to the end of Cycle 6 or 8 (24 weeks)
    Notes
    [4] - 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: No statistical analysis was planned for this primary outcome.
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    0 [6]
    0 [7]
    0 [8]
    0 [9]
    0 [10]
    0 [11]
    0 [12]
    Units: percentage of participants
    Notes
    [6] - Enrollment was permanently halted; therefore, data were not collected for this outcome measure.
    [7] - Enrollment was permanently halted; therefore, data were not collected for this outcome measure.
    [8] - Enrollment was permanently halted; therefore, data were not collected for this outcome measure.
    [9] - Enrollment was permanently halted; therefore, data were not collected for this outcome measure.
    [10] - Enrollment was permanently halted; therefore, data were not collected for this outcome measure.
    [11] - Enrollment was permanently halted; therefore, data were not collected for this outcome measure.
    [12] - Enrollment was permanently halted; therefore, data were not collected for this outcome measure.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1

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    End point title
    		 Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1 [13]
    End point description
    End point type
    Secondary
    End point timeframe
    Week 24, Week 48
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    7
    10
    6
    9
    6
    2
    4
    Units: percentage of participants
    number (not applicable)
        Week 24
    0
    0
    0
    11.1
    16.7
    0
    0
        Week 48
    0
    0
    0
    11.1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1

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    End point title
    		 Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1 [14]
    End point description
    End point type
    Secondary
    End point timeframe
    Week 24, Week 48
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    7
    10
    6
    9
    6
    2
    4
    Units: percentage of participants
    number (not applicable)
        Week 24
    0
    0
    0
    11.1
    0
    0
    0
        Week 48
    0
    0
    0
    11.1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Change in Spleen Length From Baseline in Part 1

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    End point title
    		 Change in Spleen Length From Baseline in Part 1 [15]
    End point description
    Change in spleen length measured in centimeters by manual palpation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 24, Week 48
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    6
    8
    4
    4
    4
    0 [16]
    0 [17]
    Units: centimeters
    arithmetic mean (standard deviation)
        Week 24 n=6,8,4,4,4,0,0
    -3.3 ( 2.6 )
    -5.5 ( 3.9 )
    -6.3 ( 4.6 )
    -1.8 ( 3.9 )
    -1.5 ( 1.9 )
    ( )
    ( )
        Week 48 n=2,1,2,1,1,0,0
    -5.0 ( 0.0 )
    -9.0 ( 999 )
    -6.0 ( 7.1 )
    -8.0 ( 999 )
    -5.0 ( 999 )
    ( )
    ( )
    Notes
    [16] - Number analyzed is the number of participants with available data.
    [17] - Number analyzed is the number of participants with available data.
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1

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    End point title
    		 Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1 [18]
    End point description
    Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.
    End point type
    Secondary
    End point timeframe
    Week 24, Week 48
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    7
    10
    6
    9
    6
    2
    4
    Units: percentage of participants
    number (not applicable)
        Week 24
    14.3
    60.0
    0
    0
    0
    0
    0
        Week 48
    14.3
    10.0
    16.7
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1

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    End point title
    		 Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1 [19]
    End point description
    Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.
    End point type
    Secondary
    End point timeframe
    Week 24, Week 48
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    7
    10
    6
    9
    6
    2
    4
    Units: percentage of participants
    number (not applicable)
        Week 24
    28.6
    60.0
    0
    11.1
    0
    0
    0
        Week 48
    28.6
    10.0
    16.7
    11.1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)

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    End point title
    		 Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0) [20]
    End point description
    The MFSAF v4.0 questionnaire focuses on the 7 core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety and bone pain. Subjects record symptom severity at it worst for each of the 7 symptoms on an 11-point numeric rating scale, from 0 (absent) to 10 (worst imaginable). The Total Symptom Score (TSS) is the sum of all the scores for all 7 symptoms.
    End point type
    Secondary
    End point timeframe
    Week 12, Week 24, Week 48
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    7
    10
    6
    9
    6
    2
    4
    Units: percentage of participants
    number (not applicable)
        Week 12
    42.9
    30.0
    16.7
    11.1
    16.7
    0
    0
        Week 24
    14.3
    20.0
    33.3
    11.1
    16.7
    0
    0
        Week 48
    14.3
    10.0
    16.7
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

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    End point title
    		 Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
    End point values
    		 Part 1:Ruxolitinib + Siremadlin 20 mg (AUClast for Siremadlin) Part 1:Ruxolitinib + Siremadlin 30 mg (AUClast for Siremadlin) Part 1:Ruxolitinib + Siremadlin 40 mg (AUClast for Siremadlin) Part 1:Ruxolitinib+ Rineterkib 200 mg (AUClast for Rineterkib) Part 1:Ruxolitinib + Crizanlizumab (AUClast for Crizanlizumab) Part 1: Ruxolitinib + Sabatolimab (AUClast for Sabatolimab) Part 1: Ruxolitinib + NIS793 (AUClast for NIS793)
    Number of subjects analysed
    6
    9
    5
    9
    5
    2
    4
    Units: ng*hr/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 n=6,9,5,9,5,2,4
    1520 ( 619 )
    2560 ( 1530 )
    3780 ( 1840 )
    6000 ( 5120 )
    14100000 ( 4990000 )
    34900 ( 7860 )
    103000000 ( 18700000 )
        Cycle 1 Day 5 n=6,7,5,0,0,0,0
    2230 ( 1110 )
    3340 ( 2120 )
    4390 ( 2270 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 1 n=5,6,3,0,0,0,0
    1720 ( 1020 )
    2400 ( 1150 )
    2870 ( 326 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 5 n=3,5,3,0,0,0,0
    1590 ( 577 )
    2860 ( 1680 )
    3030 ( 786 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15 n=0,0,0,9,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    15800 ( 11000 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 3 Day 1 n=0,0,0,0,5,2,3
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    20900000 ( 13000000 )
    43500 ( 9110 )
    166000000 ( 63600000 )
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1

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    End point title
    		 Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1 [21]
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    3
    4
    2
    3
    2
    2
    2
    Units: ng*hr/mL
    arithmetic mean (standard deviation)
        Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0
    999 ( 999 )
    999 ( 999 )
    344 ( 225 )
    199 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1
    546 ( 412 )
    673 ( 290 )
    498 ( 999 )
    633 ( 393 )
    440 ( 999 )
    336 ( 30.6 )
    452 ( 999 )
        Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2
    1090 ( 999 )
    999 ( 999 )
    481 ( 243 )
    729 ( 999 )
    662 ( 420 )
    999 ( 999 )
    1220 ( 637 )
        Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0
    991 ( 183 )
    616 ( 107 )
    623 ( 999 )
    913 ( 451 )
    887 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    188 ( 999 )
    999 ( 999 )
    999 ( 999 )
    859 ( 999 )
        Ruxolitinib 5 mg Cycle 1 Day 5 n=0,0,2,0,0,0,0
    999 ( 999 )
    999 ( 999 )
    245 ( 173 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0,
    465 ( 228 )
    550 ( 307 )
    441 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0
    849 ( 999 )
    901 ( 999 )
    454 ( 212 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0
    872 ( 218 )
    652 ( 218 )
    482 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 5 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    289 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 1 Day 15 n=0,0,0,2,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    592 ( 403 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 15 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0,
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    518 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 20 mg Cycle 1 Day 15 n=0,0,0,3,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    957 ( 479 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 25 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    718 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 5 mg Cycle 2 Day 1 n=0,0,1,0,0,0,0
    999 ( 999 )
    999 ( 999 )
    172 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0
    354 ( 101 )
    507 ( 225 )
    553 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0
    1040 ( 999 )
    1190 ( 214 )
    334 ( 98.7 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0
    823 ( 206 )
    727 ( 200 )
    521 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

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    End point title
    		 Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg (Cmax for Siremadlin) Part 1: Ruxolitinib + Siremadlin 30 mg (Cmax for Siremadlin) Part 1: Ruxolitinib + Siremadlin 40 mg (Cmax for Siremadlin) Part 1: Ruxolitinib + Rineterkib 200 mg (Cmax for Rineterkib) Part 1: Ruxolitinib + Crizanlizumab (Cmax for Crizanlizumab) Part 1: Ruxolitinib + Sabatolimab (Cmax for Sabatolimab) Part 1: Ruxolitinib + NIS793 (Cmax for NIS793)
    Number of subjects analysed
    6
    9
    5
    9
    5
    2
    4
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 n=6,9,5,9,5,2,4
    118 ( 32.8 )
    207 ( 122 )
    290 ( 56.1 )
    469 ( 358 )
    114000 ( 36400 )
    131 ( 17.7 )
    439000 ( 56100 )
        Cycle 1 Day 5 n=6,7,5,0,0,0,0
    161 ( 78.0 )
    284 ( 138 )
    336 ( 109 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 1 n=5,6,3,0,0,0,0
    131 ( 57.9 )
    142 ( 102 )
    268 ( 15.0 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 5 n=3,5,3,0,0,0,0
    103 ( 34.1 )
    193 ( 95.0 )
    228 ( 58.3 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15 n=0,0,0,9,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    987 ( 621 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 3 Day 1 n=0,0,0,0,5,2,3
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    114000 ( 56600 )
    150 ( 33.2 )
    743000 ( 314000 )
    No statistical analyses for this end point

    Secondary: Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1

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    End point title
    		 Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1 [22]
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    3
    4
    2
    3
    2
    2
    2
    Units: ng/mL
    arithmetic mean (standard deviation)
        Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0
    999 ( 999 )
    999 ( 999 )
    93.3 ( 26.5 )
    67.4 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1
    184 ( 159 )
    209 ( 20.8 )
    108 ( 999 )
    195 ( 41.0 )
    191 ( 999 )
    118 ( 33.0 )
    132 ( 999 )
        Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2
    334 ( 999 )
    999 ( 999 )
    119 ( 76.2 )
    193 ( 999 )
    185 ( 120 )
    999 ( 999 )
    254 ( 73.5 )
        Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0
    310 ( 131 )
    184 ( 14.8 )
    232 ( 999 )
    332 ( 33.5 )
    221 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    46.0 ( 999 )
    999 ( 999 )
    999 ( 999 )
    224 ( 999 )
        Ruxolitinib 5 mg Cycle 1 Day 5 n=0,0,2,0,0,0,0
    999 ( 999 )
    999 ( 999 )
    74.8 ( 13.5 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0
    152 ( 55.3 )
    149 ( 67.6 )
    107 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0
    252 ( 999 )
    264 ( 999 )
    172 ( 96.9 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0
    211 ( 48.8 )
    232 ( 104 )
    180 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 5 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    95.4 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 1 Day 15 n=0,0,0,2,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    158 ( 68.6 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 15 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    126 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 20 mg Cycle 1 Day 15 n=0,0,0,3,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    369 ( 83.7 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 25 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    323 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 5 mg Cycle 2 Day 1 n=0,0,1,0,0,0,0
    999 ( 999 )
    999 ( 999 )
    82.1 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0
    119 ( 66.7 )
    165 ( 29.7 )
    90.5 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0
    260 ( 999 )
    337 ( 70.7 )
    100 ( 68.9 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0
    257 ( 71.0 )
    176 ( 66.0 )
    241 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1

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    End point title
    		 Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg (Tmax for Siremadlin) Part 1: Ruxolitinib + Siremadlin 30 mg (Tmax for Siremadlin) Part 1: Ruxolitinib + Siremadlin 40 mg (Tmax for Siremadlin) Part 1: Ruxolitinib + Rineterkib 200 mg (Tmax for Rineterkib) Part 1: Ruxolitinib + Crizanlizumab (Tmax for Crizanlizumab) Part 1: Ruxolitinib + Sabatolimab (Tmax for Sabatolimab) Part 1: Ruxolitinib + NIS793 (Tmax for NIS793)
    Number of subjects analysed
    6
    9
    5
    9
    5
    2
    4
    Units: hours
    median (full range (min-max))
        Cycle 1 Day 1 n=6,9,5,9,5,2,4
    2.52 (1.83 to 23.5)
    3.00 (1.92 to 7.45)
    3.93 (2.00 to 8.00)
    3.92 (1.98 to 24.0)
    1.82 (1.50 to 2.27)
    1.84 (1.67 to 2.00)
    2.00 (1.95 to 2.98)
        Cycle 1 Day 5 n=6,7,5,0,0,0,0
    3.44 (1.83 to 4.07)
    2.90 (2.00 to 3.97)
    2.87 (1.88 to 3.03)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Cycle 2 Day 1 n=5,6,3,0,0,0,0
    1.95 (0.980 to 4.10)
    3.92 (2.83 to 23.9)
    2.88 (2.08 to 7.07)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Cycle 2 Day 5 n=3,5,3,0,0,0,0
    3.00 (2.95 to 3.17)
    2.93 (2.75 to 3.17)
    3.02 (2.92 to 3.08)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Cycle 1 Day 15 n=0,0,0,9,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    2.50 (0.500 to 4.00)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Cycle 3 Day 1 n=0,0,0,0,5,2,3
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    1.65 (0.750 to 2.13)
    2.01 (1.85 to 2.17)
    1.97 (1.92 to 2.33)
    No statistical analyses for this end point

    Secondary: Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1

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    End point title
    		 Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1 [23]
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    3
    4
    2
    3
    2
    2
    2
    Units: hours
    median (full range (min-max))
        Ruxolitinib 5 mg Cycle 1 Day 1 n=0,0,2,1,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    0.960 (0.920 to 1.00)
    0.500 (0.500 to 0.500)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 10 mg Cycle 1 Day 1 n=3,4,1,2,1,2,1
    0.550 (0.330 to 6.18)
    0.775 (0.500 to 1.08)
    0.500 (0.500 to 0.500)
    0.485 (0.470 to 0.500)
    0.580 (0.580 to 0.580)
    0.460 (0.00 to 0.920)
    1.67 (1.67 to 1.67)
        Ruxolitinib 15 mg Cycle 1 Day 1 n=1,0,2,1,2,0,2
    0.650 (0.650 to 0.650)
    999 (999 to 999)
    1.96 (1.92 to 2.00)
    0.420 (0.420 to 0.420)
    1.80 (1.75 to 1.85)
    999 (999 to 999)
    2.42 (1.08 to 3.75)
        Ruxolitinib 20 mg Cycle 1 Day 1 n=3,2,1,3,1,0,0
    0.530 (0.500 to 1.00)
    1.54 (1.08 to 2.00)
    1.00 (1.00 to 1.00)
    0.450 (0.420 to 1.03)
    1.17 (1.17 to 1.17)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 25 mg Cycle 1 Day 1 n=0,0,0,1,0,0,1
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    0.00 (0.00 to 0.00)
    999 (999 to 999)
    999 (999 to 999)
    2.00 (2.00 to 2.00)
        Ruxolitinib 5 mg Cycle 1 Day 5 n=0,0,2,0,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    0.960 (0.920 to 1.00)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 10 mg Cycle 1 Day 5 n=3,3,1,0,0,0,0
    1.00 (0.830 to 2.02)
    0.980 (0.920 to 2.03)
    1.00 (1.00 to 1.00)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 15 mg Cycle 1 Day 5 n=1,1,2,0,0,0,0
    0.970 (0.970 to 0.970)
    0.830 (0.830 to 0.830)
    0.955 (0.830 to 1.08)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 20 mg Cycle 1 Day 5 n=2,4,1,0,0,0,0
    0.925 (0.850 to 1.00)
    1.00 (0.920 to 1.08)
    0.830 (0.830 to 0.830)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 5 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    0.500 (0.500 to 0.500)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 10 mg Cycle 1 Day 15 n=0,0,0,2,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    1.98 (1.95 to 2.00)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 15 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    0.500 (0.500 to 0.500)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 20 mg Cycle 1 Day 15 n=0,0,0,3,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    0.650 (0.500 to 1.00)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 25 mg Cycle 1 Day 15 n=0,0,0,1,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    0.500 (0.500 to 0.500)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 5 mg Cycle 2 Day 1 n=0,0,1,0,0,0,0
    999 (999 to 999)
    999 (999 to 999)
    0.900 (0.900 to 0.900)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 10 mg Cycle 2 Day 1 n=2,2,1,0,0,0,0
    0.895 (0.870 to 0.920)
    1.00 (0.920 to 1.08)
    2.00 (2.00 to 2.00)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 15 mg Cycle 2 Day 1 n=1,2,2,0,0,0,0
    1.05 (1.05 to 1.05)
    1.46 (1.00 to 1.92)
    4.00 (0.920 to 7.07)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
        Ruxolitinib 20 mg Cycle 2 Day 1 n=3,3,1,0,0,0,0
    0.980 (0.880 to 1.02)
    1.02 (1.00 to 4.00)
    0.930 (0.930 to 0.930)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    999 (999 to 999)
    No statistical analyses for this end point

    Secondary: Concentration Versus Time Profile for Siremadlin in Part 1

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    End point title
    		 Concentration Versus Time Profile for Siremadlin in Part 1 [24]
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycles 1 and 2; Day 6 of Cycle 1; Days 2 and 5 of Cycles 1, 2, 3, 4, 5, and 6. Each cycle was 28 days.
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg
    Number of subjects analysed
    7
    10
    5
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1, 0 hr (pre-dose) n=6,7,5
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
        Cycle 1 Day 1, 0.5 hr n=6,8,5
    7.46 ( 6.23 )
    4.76 ( 8.02 )
    12.8 ( 21.0 )
        Cycle 1 Day 1, 1 hr n=6,9,5
    52.7 ( 27.0 )
    38.8 ( 40.9 )
    87.0 ( 73.6 )
        Cycle 1 Day 1, 2 hr n=6,9,5
    104 ( 53.3 )
    146 ( 95.1 )
    199 ( 139 )
        Cycle 1 Day 1, 3 hr n=6,9,4
    102 ( 51.8 )
    178 ( 96.3 )
    192 ( 137 )
        Cycle 1 Day 1, 4 hr n=6,9,5
    92.9 ( 44.0 )
    181 ( 116 )
    201 ( 109 )
        Cycle 1 Day 1, 8 hr n=6,9,5
    75.7 ( 36.9 )
    146 ( 77.0 )
    212 ( 55.5 )
        Cycle 1 Day 2, 24 hr n=6,10,4
    42.0 ( 23.7 )
    59.7 ( 49.4 )
    95.3 ( 41.2 )
        Cycle 1 Day 5, 0 hr (pre-dose) n=6,7,5
    43.5 ( 42.2 )
    88.4 ( 73.6 )
    77.6 ( 84.2 )
        Cycle 1 Day 5,1 hr n=6,6,5
    72.9 ( 28.3 )
    171 ( 89.8 )
    155 ( 123 )
        Cycle 1 Day 5, 2 hr n=6,7,5
    127 ( 63.7 )
    260 ( 128 )
    324 ( 112 )
        Cycle 1 Day 5, 3 hr n=6,7,5
    144 ( 74.6 )
    260 ( 130 )
    333 ( 108 )
        Cycle 1 Day 5, 4 hr n=5,7,5
    133 ( 67.4 )
    226 ( 111 )
    295 ( 97.9 )
        Cycle 1 Day 5, 8 hr n=7,8,3
    110 ( 54.3 )
    160 ( 83.1 )
    247 ( 126 )
        Cycle 1 Day 6, 24 hr n=7,8,5
    45.4 ( 35.9 )
    75.1 ( 66.5 )
    72.2 ( 90.5 )
        Cycle 2 Day 1, 0 hr (pre-dose) n=4,5,3
    0 ( 0 )
    0 ( 0 )
    0 ( 0 )
        Cycle 2 Day 1, 1 hr n=5,5,3
    71.8 ( 92.9 )
    25.5 ( 28.4 )
    32.2 ( 28.7 )
        Cycle 2 Day 1, 2 hr n=5,5,2
    116 ( 64.7 )
    100 ( 64.8 )
    144 ( 200 )
        Cycle 2 Day 1, 3 hr n=5,5,3
    111 ( 58.2 )
    146 ( 99.5 )
    178 ( 147 )
        Cycle 2 Day 1, 4 hr n=5,5,3
    114 ( 52.8 )
    158 ( 78.4 )
    164 ( 102 )
        Cycle 2 Day 1, 8 hr n=4,5,3
    90.9 ( 39.1 )
    122 ( 54.5 )
    189 ( 63.2 )
        Cycle 2 Day 2, 24 hr n=4,5,3
    67.3 ( 49.3 )
    48.5 ( 44.2 )
    31.7 ( 5.42 )
        Cycle 2 Day 5, 0 hr (pre-dose) n=4,7,3
    24.3 ( 23.8 )
    42.5 ( 50.8 )
    29.2 ( 6.67 )
        Cycle 2 Day 5, 3 hr n=3,6,3
    103 ( 34.1 )
    181 ( 89.7 )
    228 ( 58.3 )
        Cycle 2 Day 6, 24 hr n=4,5,3
    34.7 ( 13.2 )
    51.5 ( 58.3 )
    27.5 ( 6.45 )
        Cycle 3 Day 2, 0 hr (pre-dose) n=3,4,4
    43.5 ( 16.5 )
    79.1 ( 96.9 )
    39.2 ( 20.5 )
        Cycle 3 Day 5, 0 hr (pre-dose) n=5,6,3
    56.8 ( 47.9 )
    81.0 ( 73.9 )
    29.7 ( 23.3 )
        Cycle 4 Day 2, 0 hr (pre-dose) n=5,5,1
    36.3 ( 21.7 )
    63.0 ( 52.4 )
    10.9 ( 999 )
        Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,1
    40.4 ( 29.7 )
    50.1 ( 48.1 )
    10.5 ( 999 )
        Cycle 5 Day 2, 0 hr (pre-dose) n=6,4,4
    40.0 ( 29.3 )
    146 ( 180 )
    49.2 ( 25.1 )
        Cycle 5 Day 5, 0 hr (pre-dose) n=6,4,3
    78.3 ( 90.2 )
    124 ( 129 )
    32.5 ( 13.5 )
        Cycle 6 Day 2, 0 hr (pre-dose) n=5,2,1
    48.0 ( 28.2 )
    60.2 ( 37.0 )
    16.4 ( 999 )
        Cycle 6 Day 5, 0 hr (pre-dose) n=4,2,1
    79.0 ( 52.2 )
    68.9 ( 68.1 )
    9.02 ( 999 )
    No statistical analyses for this end point

    Secondary: Concentration Versus Time Profile for Rineterkib in Part 1

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    End point title
    		 Concentration Versus Time Profile for Rineterkib in Part 1 [25]
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle was 28 days.
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Rineterkib 200 mg
    Number of subjects analysed
    9
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1, 0 hr (pre-dose) n=9
    0 ( 0 )
        Cycle 1 Day 1, 0.5 hr n=9
    68.3 ( 68.8 )
        Cycle 1 Day 1, 1 hr n=8
    235 ( 343 )
        Cycle 1 Day 1, 2 hr n=8
    340 ( 229 )
        Cycle 1 Day 1, 3 hr n=9
    352 ( 244 )
        Cycle 1 Day 1, 4 hr n=9
    325 ( 173 )
        Cycle 1 Day 1, 8 hr n=7
    244 ( 128 )
        Cycle 1 Day 2, 24 hr n=9
    261 ( 419 )
        Cycle 1 Day 2, 0 hr (pre-dose) n=8
    234 ( 440 )
        Cycle 1 Day 15, 0 hr (pre-dose) n=8
    330 ( 222 )
        Cycle 1 Day 15 0.5 hr n=8
    581 ( 464 )
        Cycle 1 Day 15, 1 hr n=n=9
    735 ( 620 )
        Cycle 1 Day 15, 2 hr n=8
    749 ( 512 )
        Cycle 1 Day 15, 3 hr n=8
    789 ( 616 )
        Cycle 1 Day 15, 4 hr n=8
    771 ( 484 )
        Cycle 1 Day 15, 8 hr n=9
    633 ( 403 )
        Cycle 1 Day 16, 24 hr n=8
    528 ( 618 )
        Cycle 1 Day 16, 0 hr (pre-dose) n=8
    305 ( 222 )
        Cycle 2 Day 1, 0 hr (pre-dose) n=9
    314 ( 171 )
        Cycle 3 Day 1, 0 hr (pre-dose) n=6
    406 ( 341 )
        Cycle 4 Day 1, 0 hr (pre-dose) n=5
    402 ( 364 )
        Cycle 5 Day 1, 0 hr (pre-dose) n=3
    232 ( 165 )
        Cycle 6 Day 1, 0 hr (pre-dose) n=3
    340 ( 125 )
    No statistical analyses for this end point

    Secondary: Concentration Versus Time Profile for Crizanlizumab in Part 1

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    End point title
    		 Concentration Versus Time Profile for Crizanlizumab in Part 1 [26]
    End point description
    EOI = end of infusion
    End point type
    Secondary
    End point timeframe
    Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4, 5, 6, and 9. Each cycle was 28 days.
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Crizanlizumab
    Number of subjects analysed
    5
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1, 0 H / PRE-INFUSION n=4
    0 ( 0 )
        Cycle 1 Day 1, 1H POST EOI n=5
    114000 ( 36400 )
        Cycle 1 Day 2, 24H POST START OF INFUSION n=4
    78700 ( 10500 )
        Cycle 1 Day 8, 168H POST START OF INFUSION n=5
    28700 ( 12200 )
        Cycle 1 Day 15, 336H POST START OF INFUSION n=5
    9280 ( 4540 )
        Cycle 1 Day 15, 0 H / PRE-INFUSION n=1
    7710 ( 999 )
        Cycle 2 Day 1, 0 H / PRE-INFUSION n=5
    20700 ( 8980 )
        Cycle 2 Day 1, 1H POST EOI n=5
    135000 ( 43100 )
        Cycle 2 Day 1, 336H POST START OF INFUSION n=1,
    15500 ( 999 )
        Cycle 3 Day 1, 672H POST START OF INFUSION n=5
    8710 ( 8350 )
        Cycle 3 Day 1, 0 H / PRE-INFUSION n=5
    8710 ( 8350 )
        Cycle 3 Day 1, 1H POST EOI n=4
    103000 ( 59200 )
        Cycle 3 Day 2, 24H POST START OF INFUSION n=5
    95500 ( 42300 )
        Cycle 3 Day 8, 168H POST START OF INFUSION n=5
    37100 ( 19400 )
        Cycle 3 Day 15, 336H POST START OF INFUSION n=5
    21000 ( 17700 )
        Cycle 4 Day 1, 672H POST START OF INFUSION n=5
    5900 ( 6710 )
        Cycle 4 Day 1, 0 H / PRE-INFUSION n=5
    5900 ( 6710 )
        Cycle 4 Day 1, 1H POST EOI n=5
    128000 ( 33200 )
        Cycle 5 Day 1, 672H POST START OF INFUSION n=4
    6780 ( 7830 )
        Cycle 5 Day 1, 0 H / PRE-INFUSION n=4
    6780 ( 7830 )
        Cycle 5 Day 1, 1H POST EOI n=3
    122000 ( 29400 )
        Cycle 6 Day 1, 672H POST START OF INFUSION n=4
    6930 ( 8000 )
        Cycle 6 Day 1, 0 H / PRE-INFUSION n=4
    6930 ( 8000 )
        Cycle 6 Day 1, 1H POST EOI n=4
    128000 ( 39600 )
        Cycle 9 Day 1, 0 H / PRE-INFUSION n=3
    5500 ( 9530 )
    No statistical analyses for this end point

    Secondary: Concentration Versus Time Profile for Sabatolimab in Part 1

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    End point title
    		 Concentration Versus Time Profile for Sabatolimab in Part 1 [27]
    End point description
    EOI = end of infusion
    End point type
    Secondary
    End point timeframe
    Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Sabatolimab
    Number of subjects analysed
    2
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1, 0 H / PRE-INFUSION n=2
    0 ( 0 )
        Cycle 1 Day 1, 1H POST EOI n=1
    143 ( 999 )
        Cycle 1 Day 2, 24H POST START OF INFUSION n=2
    109 ( 13.2 )
        Cycle 1 Day 8, 168H POST START OF INFUSION n=1
    57.0 ( 999 )
        Cycle 1 Day 15, 336H POST START OF INFUSION n=2
    41.8 ( 7.28 )
        Cycle 2 Day 1, 672H POST START OF INFUSION n=2
    16.1 ( 9.16 )
        Cycle 2 Day 1, 0 H / PRE-INFUSION n=2
    16.1 ( 9.16 )
        Cycle 2 Day 1, 1H POST EOI n=1
    126 ( 999 )
        Cycle 3 Day 1, 672H POST START OF INFUSION n=2
    26.0 ( 5.09 )
        Cycle 3 Day 1, 0 H / PRE-INFUSION n=2
    26.0 ( 5.09 )
        Cycle 3 Day 1, 1H POST EOI n=2
    150 ( 33.2 )
        Cycle 3 Day 2, 24H POST START OF INFUSION n=2
    125 ( 10.6 )
        Cycle 3 Day 8, 168H POST START OF INFUSION n=2
    80.5 ( 19.1 )
        Cycle 3 Day 15, 336H POST START OF INFUSION n=2
    58.0 ( 12.3 )
        Cycle 4 Day 1, 672H POST START OF INFUSION n=1
    31.1 ( 999 )
        Cycle 4 Day 1, 0 H / PRE-INFUSION n=2
    30.0 ( 1.56 )
        Cycle 4 Day 1, 1H POST EOI n=2
    141 ( 11.3 )
        Cycle 5 Day 1, 0 H / PRE-INFUSION n=2
    32.9 ( 3.82 )
        Cycle 5 Day 1, 1H POST EOI n=2
    152 ( 9.19 )
    No statistical analyses for this end point

    Secondary: Concentration Versus Time Profile for NIS793 in Part 1

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    End point title
    		 Concentration Versus Time Profile for NIS793 in Part 1 [28]
    End point description
    EOI = end of infusion
    End point type
    Secondary
    End point timeframe
    Days 1, 2, 4, 8, 11, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    4
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1, 0 H / PRE-INFUSION n=4
    0 ( 0 )
        Cycle 1 Day 1, 1H POST EOI n=4
    439000 ( 56100 )
        Cycle 1 Day 2, 24H POST START OF INFUSION n=4
    349000 ( 52800 )
        Cycle 1 Day 4, 72H POST START OF INFUSION n=4
    279000 ( 48400 )
        Cycle 1 Day 8, 168H POST START OF INFUSION n=3
    196000 ( 31000 )
        Cycle 1 Day 11, 240H POST START OF INFUSION n=4
    183000 ( 45400 )
        Cycle 1 Day 15, 336H POST START OF INFUSION n=4
    161000 ( 37500 )
        Cycle 2 Day 1, 504H POST START OF INFUSION n=4
    132000 ( 33300 )
        Cycle 2 Day 1, 0 H / PRE-INFUSION n=4
    132000 ( 33300 )
        Cycle 3 Day 1, 0 H / PRE-INFUSION n=3
    187000 ( 61000 )
        Cycle 3 Day 1, 1H POST EOI n=3
    743000 ( 314000 )
        Cycle 3 Day 2, 24H POST START OF INFUSION n=2
    632000 ( 17000 )
        Cycle 3 Day 4, 72H POST START OF INFUSION n=3
    448000 ( 114000 )
        Cycle 3 Day 8, 168H POST START OF INFUSION n=3
    383000 ( 103000 )
        Cycle 3 Day 11, 240H POST START OF INFUSION n=2
    262000 ( 93300 )
        Cycle 3 Day 15, 336H POST START OF INFUSION n=3
    265000 ( 51500 )
        Cycle 4 Day 1, 504H POST START OF INFUSION n=1
    281000 ( 999 )
        Cycle 4 Day 1, 0 H / PRE-INFUSION n=2
    232000 ( 70000 )
        Cycle 5 Day 1, 0 H / PRE-INFUSION n=1
    280000 ( 999 )
    No statistical analyses for this end point

    Secondary: Concentration Versus Time Profile for Ruxolitinib in Part 1

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    End point title
    		 Concentration Versus Time Profile for Ruxolitinib in Part 1 [29]
    End point description
    End point type
    Secondary
    End point timeframe
    Days 1, 2, 5, 6, and 15 of Cycles 1 and 2; Day 16 of Cycle 1; Days 1, 2, and 15 of Cycle 3; Days 1 and 5 of Cycles 4, 5, and 6. Each cycle was 28 days.
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Applicable to Part 1 only.
    End point values
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 1: Ruxolitinib + NIS793
    Number of subjects analysed
    7
    8
    6
    8
    4
    2
    4
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1, 0 hr (pre-dose) n=6,6,5,7,3,2,4
    34.7 ( 17.8 )
    21.3 ( 14.5 )
    11.8 ( 13.4 )
    20.1 ( 16.1 )
    12.9 ( 6.31 )
    51.2 ( 61.0 )
    37.9 ( 48.4 )
        Cycle 1 Day 1, 0.5 hr n=6,5,6,8,2,2,3
    284 ( 128 )
    152 ( 91.1 )
    95.7 ( 63.2 )
    185 ( 100 )
    107 ( 119 )
    57.1 ( 44.0 )
    108 ( 128 )
        Cycle 1 Day 1, 1 hr n=6,6,6,7,2,2,3
    240 ( 78.9 )
    167 ( 51.7 )
    124 ( 64.5 )
    192 ( 106 )
    65.7 ( 59.9 )
    110 ( 44.1 )
    164 ( 140 )
        Cycle 1 Day 1, 2 hr n=6,6,6,7,2,2,3
    174 ( 55.3 )
    143 ( 48.6 )
    98.9 ( 46.2 )
    140 ( 112 )
    170 ( 140 )
    72.7 ( 4.10 )
    187 ( 105 )
        Cycle 1 Day 1, 3 hr n=6,6,5,8,2,2,3
    125 ( 36.6 )
    114 ( 42.1 )
    62.4 ( 31.1 )
    97.4 ( 75.7 )
    124 ( 91.0 )
    54.4 ( 10.4 )
    184 ( 77.9 )
        Cycle 1 Day 1, 4 hr n=6,6,6,8,2,2,3
    93.2 ( 26.5 )
    77.8 ( 40.0 )
    50.2 ( 23.4 )
    59.2 ( 46.1 )
    101 ( 81.2 )
    28.3 ( 7.28 )
    190 ( 58.4 )
        Cycle 1 Day 1, 8 hr n=6,6,6,8,4,2,3
    51.6 ( 18.7 )
    32.2 ( 19.1 )
    24.0 ( 15.0 )
    29.9 ( 19.8 )
    39.5 ( 29.2 )
    7.75 ( 1.52 )
    44.4 ( 35.3 )
        Cycle 1 Day 2, 0 hr (pre-dose) n=7,6,4,8,1,1,0
    18.2 ( 13.0 )
    13.4 ( 11.1 )
    11.2 ( 16.2 )
    17.6 ( 19.9 )
    30.3 ( 999 )
    0 ( 999 )
    999 ( 999 )
        Cycle 1 Day 5, 0 hr (pre-dose) n=6,8,6,0,0,0,0
    15.5 ( 13.9 )
    14.7 ( 14.0 )
    9.33 ( 10.6 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 5, 1 hr n=6,7,6,0,0,0,0
    160 ( 79.5 )
    221 ( 83.7 )
    130 ( 66.6 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 5, 2 hr n=6,8,6,0,0,0,0
    149 ( 64.0 )
    140 ( 45.6 )
    90.0 ( 41.4 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 5, 3 hr n=6,8,6,0,0,0,0
    104 ( 45.2 )
    100 ( 39.1 )
    61.8 ( 31.7 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 5, 4 hr n=6,8,6,0,0,0,0
    81.4 ( 38.4 )
    71.2 ( 30.1 )
    34.1 ( 16.1 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 5, 8 hr n=6,8,4,0,0,0,0
    37.6 ( 22.6 )
    22.9 ( 13.7 )
    16.2 ( 13.4 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 6, 0 hr (pre-dose) n=6,7,5,0,0,0,0
    11.5 ( 12.1 )
    37.8 ( 63.4 )
    6.28 ( 9.31 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15, 0 hr (pre-dose) n=7,8,4,7,3,2,0
    23.2 ( 34.0 )
    23.6 ( 19.8 )
    11.2 ( 17.4 )
    11.9 ( 14.2 )
    12.6 ( 10.1 )
    4.06 ( 2.28 )
    999 ( 999 )
        Cycle 1 Day 15, 0.5 hr n=0,0,0,7,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    231 ( 115 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15, 1 hr n=0,0,0,8,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    194 ( 139 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15, 2 hr n=0,0,0,7,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    126 ( 58.7 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15, 3 hr n=0,0,0,7,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    103 ( 59.6 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15, 4 hr n=0,0,0,7,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    76.3 ( 53.5 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 15, 8 hr n=0,0,0,8,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    27.9 ( 21.7 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 1 Day 16, 0 hr (pre-dose) n=0,0,0,6,0,0,0
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    14.4 ( 15.2 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 1, 0 hr (pre-dose) n=6,7,5,8,4,2,3
    25.9 ( 23.4 )
    19.3 ( 18.8 )
    11.4 ( 20.7 )
    45.7 ( 108 )
    13.7 ( 4.84 )
    28.4 ( 39.1 )
    65.1 ( 88.9 )
        Cycle 2 Day 1, 1 hr n=6,7,5,0,0,0,0
    212 ( 89.8 )
    186 ( 113 )
    114 ( 82.4 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 1, 2 hr n=6,7,4,0,0,0,0
    144 ( 76.0 )
    165 ( 82.2 )
    56.2 ( 30.9 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 1, 3 hr n=6,7,5,0,0,0,0
    108 ( 50.8 )
    127 ( 61.7 )
    50.3 ( 26.4 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 1, 4 hr n=5,7,5,0,0,0,0
    89.9 ( 39.8 )
    106 ( 39.5 )
    45.6 ( 25.8 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 1, 8 hr n=4,6,5,0,0,0,0
    47.3 ( 31.5 )
    45.8 ( 19.4 )
    30.9 ( 28.1 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 2, 0 hr (pre-dose) n=3,6,5,0,0,0,0
    74.0 ( 62.3 )
    19.2 ( 19.7 )
    13.9 ( 20.5 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 5, 0 hr (pre-dose) n=3,8,4,0,0,0,0
    15.4 ( 6.29 )
    15.2 ( 11.3 )
    4.45 ( 4.57 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 6, 0 hr (pre-dose) n=4,5,4,0,0,0,0
    7.36 ( 7.32 )
    46.8 ( 80.0 )
    2.40 ( 2.74 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 2 Day 15, 0 hr (pre-dose) n=6,8,3,0,1,2,0
    22.4 ( 17.2 )
    22.1 ( 22.7 )
    1.93 ( 1.65 )
    999 ( 999 )
    63.6 ( 999 )
    7.95 ( 8.14 )
    999 ( 999 )
        Cycle 3 Day 1, 0 hr (pre-dose) n=7,7,4,6,4,2,2
    24.2 ( 15.5 )
    23.2 ( 21.8 )
    4.50 ( 4.03 )
    11.1 ( 10.9 )
    12.0 ( 6.36 )
    2.44 ( 1.46 )
    84.6 ( 96.8 )
        Cycle 3 Day 2, 0 hr (pre-dose) n=5,6,3,0,0,0,0
    12.6 ( 13.9 )
    31.9 ( 38.9 )
    2.33 ( 1.57 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 3 Day 15, 0 hr (pre-dose) n=5,5,2,0,4,2,0
    18.7 ( 18.4 )
    45.2 ( 41.5 )
    3.95 ( 4.10 )
    999 ( 999 )
    10.9 ( 6.89 )
    12.5 ( 9.14 )
    999 ( 999 )
        Cycle 4 Day 1, 0 hr (pre-dose) n=7,5,3,5,4,1,1
    17.5 ( 18.2 )
    20.9 ( 22.2 )
    4.53 ( 6.44 )
    18.2 ( 33.8 )
    14.0 ( 7.81 )
    2.94 ( 999 )
    24.4 ( 999 )
        Cycle 4 Day 5, 0 hr (pre-dose) n=5,6,3,0,0,0,0
    13.6 ( 13.7 )
    9.12 ( 13.5 )
    7.99 ( 11.4 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 5 Day 1, 0 hr (pre-dose) n=7,6,4,3,3,0,0
    16.4 ( 16.1 )
    12.7 ( 12.0 )
    5.30 ( 5.94 )
    10.3 ( 13.6 )
    20.1 ( 23.0 )
    999 ( 999 )
    999 ( 999 )
        Cycle 5 Day 5, 0 hr (pre-dose) n=5,3,3,0,0,0,0
    26.6 ( 16.4 )
    9.54 ( 13.2 )
    2.79 ( 2.46 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Cycle 6 Day 1, 0 hr (pre-dose) n=4,4,2,3,3,0,0
    15.8 ( 19.5 )
    17.0 ( 19.7 )
    0.608 ( 0.0672 )
    21.9 ( 23.2 )
    27.3 ( 32.8 )
    999 ( 999 )
    999 ( 999 )
        Cycle 6 Day 5, 0 hr (pre-dose) n=3,4,2,0,0,0,0
    24.8 ( 19.9 )
    11.5 ( 8.34 )
    0.957 ( 0.528 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment until end of study treatment plus post-treatment safety follow-up, up to a maximum duration of approximately 44 months.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 20 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 40 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Siremadlin
    Reporting group description
    		 Total

    Reporting group title
    Part 1: Ruxolitinib + Siremadlin 30 mg
    Reporting group description
    		 Dose escalation of siremadlin added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Rineterkib 200 mg
    Reporting group description
    		 Dose escalation of rineterkib added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + NIS793
    Reporting group description
    		 Safety run-in of NIS793 added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Crizanlizumab
    Reporting group description
    		 Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib

    Reporting group title
    Part 1: Ruxolitinib + Sabatolimab
    Reporting group description
    		 Safety run-in of sabatolimab added to existing stable dose of ruxolitinib

    Reporting group title
    Part 2: Ruxolitinib
    Reporting group description
    		 Existing stable dose of ruxolitinib as control for Part 2

    Reporting group title
    All Subjects
    Reporting group description
    		 All Subjects

    Serious adverse events
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Siremadlin Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + NIS793 Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 2: Ruxolitinib All Subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 7 (28.57%)
    4 / 6 (66.67%)
    9 / 23 (39.13%)
    3 / 10 (30.00%)
    3 / 9 (33.33%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    15 / 45 (33.33%)
         number of deaths (all causes)
    0
    3
    3
    0
    1
    0
    0
    0
    0
    4
         number of deaths resulting from adverse events
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Prostate cancer
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm rupture
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine prolapse
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Body temperature increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Product administration error
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    2 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Neutrophilic dermatosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Cystitis noninfective
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Epididymitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    1 / 2 (50.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part 1: Ruxolitinib + Siremadlin 20 mg Part 1: Ruxolitinib + Siremadlin 40 mg Part 1: Ruxolitinib + Siremadlin Part 1: Ruxolitinib + Siremadlin 30 mg Part 1: Ruxolitinib + Rineterkib 200 mg Part 1: Ruxolitinib + NIS793 Part 1: Ruxolitinib + Crizanlizumab Part 1: Ruxolitinib + Sabatolimab Part 2: Ruxolitinib All Subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    6 / 6 (100.00%)
    23 / 23 (100.00%)
    10 / 10 (100.00%)
    9 / 9 (100.00%)
    3 / 4 (75.00%)
    6 / 6 (100.00%)
    2 / 2 (100.00%)
    0 / 1 (0.00%)
    43 / 45 (95.56%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    2
    2
    0
    0
    2
    0
    0
    0
    4
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    0
    0
    0
    2
    Vascular disorders
    Capillary leak syndrome
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Angiopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Hypertension
         subjects affected / exposed
    4 / 7 (57.14%)
    0 / 6 (0.00%)
    4 / 23 (17.39%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    5 / 45 (11.11%)
         occurrences all number
    4
    0
    4
    0
    0
    0
    1
    0
    0
    5
    Hypotension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Venous thrombosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Chills
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    Chest pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    2
    Asthenia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    3 / 9 (33.33%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 45 (8.89%)
         occurrences all number
    0
    0
    0
    0
    3
    0
    2
    0
    0
    5
    Chest discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    5 / 23 (21.74%)
    3 / 10 (30.00%)
    1 / 9 (11.11%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    8 / 45 (17.78%)
         occurrences all number
    0
    2
    6
    4
    2
    1
    1
    0
    0
    10
    Oedema peripheral
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    3 / 23 (13.04%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 45 (8.89%)
         occurrences all number
    1
    1
    3
    1
    0
    0
    2
    0
    0
    5
    Mucosal inflammation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Malaise
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    5 / 7 (71.43%)
    2 / 6 (33.33%)
    8 / 23 (34.78%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    8 / 45 (17.78%)
         occurrences all number
    10
    2
    15
    3
    0
    0
    0
    0
    0
    15
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea exertional
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    1
    0
    0
    3
    Dyspnoea
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    2 / 23 (8.70%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 45 (8.89%)
         occurrences all number
    2
    1
    3
    0
    0
    0
    2
    0
    0
    5
    Cough
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    2
    0
    2
    0
    1
    0
    0
    0
    0
    3
    Epistaxis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 45 (8.89%)
         occurrences all number
    0
    0
    0
    0
    1
    4
    1
    0
    0
    6
    Hypoxia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Nasal cavity mass
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Confusional state
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Sleep disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    2 / 23 (8.70%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 4 (25.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    6 / 45 (13.33%)
         occurrences all number
    0
    2
    2
    0
    1
    1
    2
    0
    0
    6
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    3
    4
    1
    1
    0
    0
    0
    0
    5
    Amylase increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    0
    6
    5
    0
    0
    1
    0
    0
    7
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    0
    1
    0
    2
    0
    0
    0
    0
    3
    Blood creatinine increased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    6
    6
    1
    0
    0
    0
    0
    7
    Blood folate decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    0
    2
    Blood potassium increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    0
    0
    0
    2
    Lipase increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    0
    7
    6
    0
    0
    1
    0
    0
    8
    Heart sounds abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Heart rate decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Cardiac murmur
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    2
    0
    0
    3
    White blood cell count decreased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    0
    0
    0
    2
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Platelet count decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    1
    1
    0
    2
    0
    0
    0
    3
    Fall
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    1
    0
    0
    2
    Incorrect dose administered
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Ligament sprain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Tendon rupture
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Transfusion reaction
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    2
    2
    0
    0
    0
    0
    0
    2
    Skin abrasion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Skin wound
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Cardiac failure
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Palpitations
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Pericardial effusion
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Sinus bradycardia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    2 / 23 (8.70%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    1
    2
    0
    0
    0
    2
    0
    0
    4
    Dysaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 6 (33.33%)
    2 / 23 (8.70%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 45 (8.89%)
         occurrences all number
    0
    4
    4
    0
    1
    1
    0
    0
    0
    6
    Headache
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 6 (0.00%)
    4 / 23 (17.39%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    7 / 45 (15.56%)
         occurrences all number
    3
    0
    4
    1
    1
    0
    3
    0
    0
    8
    Migraine
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Sciatica
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Polyneuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 7 (42.86%)
    5 / 6 (83.33%)
    15 / 23 (65.22%)
    7 / 10 (70.00%)
    1 / 9 (11.11%)
    2 / 4 (50.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    19 / 45 (42.22%)
         occurrences all number
    3
    19
    31
    9
    1
    2
    1
    0
    0
    35
    Lymphopenia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    1
    0
    0
    3
    Neutropenia
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 6 (50.00%)
    11 / 23 (47.83%)
    8 / 10 (80.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    11 / 45 (24.44%)
         occurrences all number
    0
    4
    18
    14
    0
    0
    0
    0
    0
    18
    Splenomegaly
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    1 / 7 (14.29%)
    6 / 6 (100.00%)
    14 / 23 (60.87%)
    7 / 10 (70.00%)
    2 / 9 (22.22%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    2 / 2 (100.00%)
    0 / 1 (0.00%)
    19 / 45 (42.22%)
         occurrences all number
    1
    16
    29
    12
    3
    0
    2
    2
    0
    36
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Erythema of eyelid
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Eye pain
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Macular oedema
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Photopsia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    2
    Retinal haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    0
    0
    0
    2
    Retinal detachment
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Presbyopia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Visual impairment
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Visual acuity reduced
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Serous retinopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Retinopathy
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    1
    1
    0
    1
    0
    0
    0
    0
    2
    Abdominal pain upper
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    2
    0
    3
    1
    0
    0
    0
    0
    0
    3
    Constipation
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    4 / 23 (17.39%)
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    5 / 45 (11.11%)
         occurrences all number
    3
    3
    8
    2
    1
    0
    0
    0
    0
    9
    Diarrhoea
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 6 (0.00%)
    5 / 23 (21.74%)
    2 / 10 (20.00%)
    6 / 9 (66.67%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    13 / 45 (28.89%)
         occurrences all number
    6
    0
    9
    3
    6
    0
    5
    0
    0
    20
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    1
    0
    0
    3
    Dry mouth
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    0
    0
    0
    2
    Abdominal distension
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Flatulence
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Gingival bleeding
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Vomiting
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    3 / 23 (13.04%)
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    5 / 45 (11.11%)
         occurrences all number
    1
    0
    3
    2
    4
    0
    2
    0
    0
    9
    Oral dysaesthesia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Nausea
         subjects affected / exposed
    6 / 7 (85.71%)
    3 / 6 (50.00%)
    13 / 23 (56.52%)
    4 / 10 (40.00%)
    3 / 9 (33.33%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    18 / 45 (40.00%)
         occurrences all number
    16
    11
    34
    7
    3
    0
    2
    0
    0
    39
    Mouth haemorrhage
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Dermatitis acneiform
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Blister
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Alopecia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Actinic keratosis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Night sweats
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    2 / 23 (8.70%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    2
    3
    5
    0
    0
    1
    0
    0
    0
    6
    Rash
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    0
    0
    0
    2
    Pruritus
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    1
    0
    0
    3
    Pain of skin
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Skin discolouration
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Skin disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Skin lesion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Skin ulcer
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Trichodysplasia spinulosa
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Gouty arthritis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    2
    Bone pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    5 / 45 (11.11%)
         occurrences all number
    2
    0
    2
    0
    2
    1
    1
    0
    0
    6
    Back pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    1
    0
    0
    2
    Arthropathy
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Arthralgia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    2 / 9 (22.22%)
    0 / 4 (0.00%)
    2 / 6 (33.33%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    5 / 45 (11.11%)
         occurrences all number
    0
    2
    2
    0
    3
    0
    3
    0
    0
    8
    Muscle spasms
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    1 / 4 (25.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 45 (8.89%)
         occurrences all number
    1
    0
    1
    0
    1
    2
    1
    0
    0
    5
    Muscle tightness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Muscular weakness
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Sacroiliac joint dysfunction
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Candida infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    COVID-19
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    3 / 23 (13.04%)
    2 / 10 (20.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    3 / 45 (6.67%)
         occurrences all number
    0
    1
    3
    2
    0
    0
    0
    0
    0
    3
    Erysipelas
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Furuncle
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Eye infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    0
    0
    0
    2
    Tooth infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    1 / 4 (25.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    0
    0
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    0
    0
    0
    2
    Mucosal infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    3
    3
    0
    0
    0
    0
    0
    3
    Wound infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    0
    0
    1
    1
    1
    0
    0
    0
    0
    2
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 6 (0.00%)
    3 / 23 (13.04%)
    0 / 10 (0.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    4 / 45 (8.89%)
         occurrences all number
    5
    0
    5
    0
    1
    0
    0
    0
    0
    6
    Dehydration
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    1
    Gout
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    0 / 23 (0.00%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 6 (0.00%)
    2 / 23 (8.70%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    2 / 45 (4.44%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    0
    0
    0
    2
    Hyperuricaemia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 6 (16.67%)
    4 / 23 (17.39%)
    2 / 10 (20.00%)
    1 / 9 (11.11%)
    0 / 4 (0.00%)
    1 / 6 (16.67%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    6 / 45 (13.33%)
         occurrences all number
    1
    1
    4
    2
    1
    0
    1
    0
    0
    6
    Hypokalaemia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 7 (0.00%)
    0 / 6 (0.00%)
    1 / 23 (4.35%)
    1 / 10 (10.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    0
    0
    0
    1
    Iron overload
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 6 (16.67%)
    1 / 23 (4.35%)
    0 / 10 (0.00%)
    0 / 9 (0.00%)
    0 / 4 (0.00%)
    0 / 6 (0.00%)
    0 / 2 (0.00%)
    0 / 1 (0.00%)
    1 / 45 (2.22%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    0
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jul 2019
    This amendment: excluded subjects eligible for allogeneic hematopoeitic stem cell treatment (ASCT); clarified that any subjects scheduled for ASCT during the study were to be discontinued; aligned updated information available from the sabatolimab (MBG453) Investigator’s Brochure to use highly effective forms of contraception for women of child-bearing potential (WOCBP) for up to 150 days for subjects on study treatment that included sabatolimab; clarified that the safety follow-up for subjects on study treatment that included sabatolimab was up to 150 days; safety follow-ups were to be conducted at 30, 90, and 150 days; excluded all forms of hormonal contraception for WOCBP (for consistency, hormonal contraception was excluded from all arms of the study); excluded subjects who could not discontinue drugs that strongly induce or inhibit CYP2C9; added strong inducers or inhibitors of CYP2C9 as prohibited medications, advised caution on the use of moderate inducers or inhibitors; clarified for the safety run-in of crizanlizumab and sabatolimab arms of the study in Part 1 that if 2 subjects experienced a dose-limiting toxicity (DLT) in either arm, then further enrolment into that arm would stop, and the treatment combination would not open in Part 2; clarified that intra-subject dose escalation was not allowed; added additional electrocardiogram (ECG) safety monitoring for any QTc interval prolongation > 60 msecs from baseline; added a recommendation to protect skin from solar UV radiation if subjects were on study treatment that contained siremadlin; clarified that the Patient Global Impression of Change (PGIC) patient-reported outcome (PRO) was not required at screening; clarified that urine pregnancy tests would be performed monthly for all pre-menopausal women who were not surgically sterile; added further hypothetical on-study data scenarios to the Bayesian model used to guide dose escalation in Part 1 for siremadlin in combination with ruxolitinib.
    17 Feb 2020
    This amendment: clarified definition of accelerated phase for progression free survival; clarified that subjects who had participated in the CINC424H12201 study could participate in a subsequent part of the study; removed exclusion of subjects treated with hematopoietic colony-stimulating growth factors; excluded subjects who used live vaccines within 30 days of starting any study treatment; added live vaccines as prohibited medication for study treatment arms containing crizanlizumab or sabatolimab; excluded subjects who used systemic steroid therapy and other immunosuppressive drugs (> 10 mg/day prednisone or equivalent) within 14 days prior to first dose of study treatment; added use of systemic steroid therapy as prohibited medication, except for treatment of infusion reaction, treatment of immune-related adverse events, prophylaxis against imaging contrast dye allergy, replacement-dose steroids in the setting of adrenal insufficiency (providing this was ≤ 10 mg/day prednisone or equivalent), or treatment of transient exacerbation of other underlying diseases such as chronic obstructive pulmonary disease requiring treatment for ≤ 3 weeks; excluded subjects who used anticoagulation or antiplatelet therapy within 10 days of prior to first dose of study treatment and subjects who had bleeding events within 6 months prior to first dose of study treatment; updated the prohibition of anticoagulation therapy to allow the use of low molecular weight heparin or direct oral anti-coagulants if used at sub-therapeutic doses; added erythropoietin stimulating agents (ESAs) as prohibited medication; updated the dose modification tables specific to the novel agents to remove any reference to ruxolitinib; allowed subjects in Part 1 to continue on study treatment after the planned 6 cycles if the subject was still deriving clinical benefit; defined “overall safety period.”
    28 Apr 2020
    This amendment: updated Exclusion Criterion #8 to exclude patients with known history of human immunodeficiency virus (HIV) as an overall positive benefit risk ratio to include HIV patients with the various novel combination treatments could not be determined at that stage. In addition, antiretroviral therapy (ART) regimen including strong CYP3A4 inhibitors could lead to the potential drug-drug interaction of one or more study medications; extended the restrictions on the use of live vaccines until the end of the follow-up period after the last dose of crizanlizumab and sabatolimab, which was within 5 half-lives of the study treatment; guidance was added on the criteria for sabatolimab dose management for dermatological adverse drug reactions (ADRs) and non-immune related toxicities; added guidance that subjects should be monitored carefully for any skin toxicity or mucositis, and that study treatment should be discontinued for any suspected case of Stevens-Johnson syndrome (SJS), or Lyell syndrome/toxic epidermal necrolysis (TEN).
    25 Aug 2020
    This amendment: added two novel compounds to Part 1 of the protocol: LTT462, which is a potent, selective, inhibitor of extracellular signal-regulated kinase 1 (ERK1) and extracellular signal regulated kinase 2 (ERK2), and NIS793, which is an anti-transforming growth factor beta (anti-TGFβ) monoclonal antibody (mAb); added additional cycles throughout the protocol, where applicable; increased the number of subjects required for Part 2 from 15 subjects per arm to 25 subjects per arm to ensure the acceptable futility probability for applying the futility rule in multiple arms.
    23 Feb 2021
    This amendment: updated the study design to allow 1) Part 2 (Selection) to be conducted for each combination treatment once the combination treatment was determined to be safe and tolerable in Part 1, and 2) to allow more than one combination treatment selected in Part 2 to enter Part 3 (Expansion); added an interim analysis per combination treatment after at least 10 subjects completed 24 weeks of study treatment in Part 2 to allow for a seamless transition into Part 3 if an efficacy threshold was reached; reduced the number of pharmacokinetic and pharmacodynamic samples collected, including removal of a few assessment visits in Part 2 and Part 3 of the study; included specific requirements for conducting the study in China, Japan, and USA.
    20 Jul 2021
    This amendment: updated the eligibility criteria to reduce the time required for patients to be treated with ruxolitinib from “at least 24 weeks” to “at least 12 weeks” prior to first dose of study treatment, and also to reduce the time required for patients to be on a stable prescribed dose of ruxolitinib (no dose adjustments) prior to first dose of study treatment from “≥ 8 weeks” to “≥ 4 weeks”; provided more detailed guidance regarding dose modifications of siremadlin, rineterkib and NIS793 in case of toxicity including to allow patients to continue on study treatment at a reduced dose level for siremadlin or rineterkib or, at a reduced frequency for NIS793 if patients derived clinical benefits as per investigator’s judgement; additional precautionary measures have been implemented based on emerging new NIS793-related preclinical safety findings including update of exclusion criteria for impaired cardiac function and addition of cardiac imaging and cardiac enzymes safety assessments during treatment to enhance cardio-vascular mitigation; additional guidance on dose discontinuation for NIS793 in case of Drug-induced liver injury (DILI); removed the collection of bone marrow aspirate for megakaryocyte characterization in all parts of the study; updated the withdrawal of consent language as per the latest Novartis protocol template.
    11 Jan 2022
    This amendment: allowed patients requiring packed red blood cell (PRBC) transfusions at any timepoint prior to first dose of study treatment to participate in all parts of the study; added details on the endpoints definitions to assess the following secondary objectives (i) changes in symptoms of myelofibrosis using the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 scale and (ii) changes in spleen volume to include pre-defined threshold of improvement; added a new strength of rineterkib to allow additional doses of rineterkib to be tested if ever required; updated exclusion criteria to provide a more comprehensive guidance on the time gap between administration of monoclonal antibody or immunoglobulin-based agent for NIS793, crizanlizumab or sabatolimab arms (within 1 year) and rineterkib or siremadlin arms (within ≤4 weeks of screening or ≤5 half-lives, whichever was shorter); added new biomarkers specific for NIS793 and sabatolimab to assess the impact of TGFβ and TIM-3 inhibition with NIS793 and MBG453 on various immune cells.
    05 Oct 2022
    This amendment reflected the changes in study conduct that were a result of the permanent enrollment halt decision by Novartis. These changes included adding an extension treatment phase and reduction of study assessments to decrease subjects’ burden in Part 1.
    05 Dec 2023
    This amendment increased the duration of the extension treatment phase for the remaining patients to a maximum of 21 cycles.

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results.
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