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    Clinical Trial Results:
    GRAVITAS-309: A Phase 2/3 Study of Itacitinib and Corticosteroids as Initial Treatment for Chronic Graft-Versus-Host Disease

    Summary
    EudraCT number
    		 2018-001606-29
    Trial protocol
    		 BE   GB   FR   SE   DE   PL   DK   ES   GR   FI   IT  
    Global end of trial date
    03 Nov 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    09 Feb 2025
    First version publication date
    25 Oct 2024
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Results summary revised to align with changes made to ClinicalTrials.gov summary.

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    INCB 39110-309
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Incyte Corporation
    Sponsor organisation address
    1801 Augustine Cutoff Drive, Wilmington, United States, 19803
    Public contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
    Scientific contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.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
    03 Nov 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    03 Nov 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Part 1 and Part 1 expansion: to identify an appropriate dose of itacitinib in combination with corticosteroids as initial treatment for moderate or severe chronic graft-versus-host disease (cGVHD). Part 2: to compare the efficacy of itacitinib versus placebo in combination with corticosteroids as initial treatment for moderate or severe cGVHD.
    Protection of trial subjects
    This study was to be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws and country-specific regulations in which the study was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    17 Jan 2019
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 24 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    United States: 57
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Germany: 27
    Country: Number of subjects enrolled
    Greece: 10
    Country: Number of subjects enrolled
    Italy: 22
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Spain: 20
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    Canada: 6
    Country: Number of subjects enrolled
    Israel: 3
    Worldwide total number of subjects
    160
    EEA total number of subjects
    90
    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)
    123
    From 65 to 84 years
    37
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study was conducted at 65 study centers in Austria, Belgium, Canada, Denmark, Germany, Greece, Israel, Italy, Poland, Spain, Switzerland, United Kingdom, and the United States.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part 1: itacitinib 200 mg QD + CS
    Arm description
    		 Participants were treated with oral itacitinib 200 milligrams (mg) once daily (QD) + corticosteroids (CS) for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mgh/kilogram (kg) QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (chronic graft-versus-host disease [cGVHD] progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    corticosteroids (methylprednisolone, prednisone)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    starting dose 0.5-1.0 mg/kg per day prednisone (or methylprednisolone equivalent to prednisone dose); may have varied based on institutional practice

    Investigational medicinal product name
    itacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Prolonged-release tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two 100-mg sustained-release tablets taken orally

    Arm title
    		 Part 1: itacitinib 300 mg QD + CS
    Arm description
    		 Participants were treated with oral itacitinib 300 mg QD + CS for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    corticosteroids (methylprednisolone, prednisone)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    starting dose 0.5-1.0 mg/kg per day prednisone (or methylprednisolone equivalent to prednisone dose); may have varied based on institutional practice

    Investigational medicinal product name
    itacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Prolonged-release tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Three 100-mg sustained-release tablets taken orally

    Arm title
    		 Part 1 Expansion: itacitinib 300 mg QD + CS
    Arm description
    		 Participants were treated with oral itacitinib 300 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    corticosteroids (methylprednisolone, prednisone)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    starting dose 0.5-1.0 mg/kg per day prednisone (or methylprednisolone equivalent to prednisone dose); may have varied based on institutional practice

    Investigational medicinal product name
    itacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Prolonged-release tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Three 100-mg sustained-release tablets taken orally

    Arm title
    		 Part 1 Expansion: itacitinib 400 mg QD + CS
    Arm description
    		 Participants were treated with oral itacitinib 400 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    corticosteroids (methylprednisolone, prednisone)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    starting dose 0.5-1.0 mg/kg per day prednisone (or methylprednisolone equivalent to prednisone dose); may have varied based on institutional practice

    Investigational medicinal product name
    itacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Prolonged-release tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Two 100-mg sustained-release tablets taken orally

    Arm title
    		 Part 1 Expansion: itacitinib 300 mg BID + CS
    Arm description
    		 Participants were treated with oral itacitinib 300 mg twice daily (BID) + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). The itacitanib dose could have been decreased to 200 mg BID if a boundary was reached during safety run-in. This treatment group was discontinued due to concern of a potential increase in relapse rate. Participants in this treatment group who were ongoing were allowed to reduce to 400 mg QD plus CS. Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    corticosteroids (methylprednisolone, prednisone)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    starting dose 0.5-1.0 mg/kg per day prednisone (or methylprednisolone equivalent to prednisone dose); may have varied based on institutional practice

    Investigational medicinal product name
    itacitinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Prolonged-release tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Three 100-mg sustained-release tablets taken orally

    Arm title
    		 Part 1 Expansion: CS monotherapy
    Arm description
    		 Participants were treated with CS alone. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    corticosteroids (methylprednisolone, prednisone)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    starting dose 0.5-1.0 mg/kg per day prednisone (or methylprednisolone equivalent to prednisone dose); may have varied based on institutional practice

    Number of subjects in period 1
    		Part 1: itacitinib 200 mg QD + CS Part 1: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Started
    11
    10
    35
    39
    29
    36
    Completed
    6
    5
    3
    2
    1
    1
    Not completed
    5
    5
    32
    37
    28
    35
         Consent withdrawn by subject
    2
    -
    2
    4
    2
    3
         Physician decision
    -
    -
    4
    3
    2
    3
         Disease Progression; cGVHD Flare
    -
    -
    -
    -
    -
    1
         Death
    2
    3
    9
    8
    4
    5
         Study Terminated by Sponsor
    -
    2
    17
    20
    20
    23
         Lost to follow-up
    1
    -
    -
    1
    -
    -
         Discontinued Treatment and Terminated CS Tapering
    -
    -
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1: itacitinib 200 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 200 milligrams (mg) once daily (QD) + corticosteroids (CS) for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mgh/kilogram (kg) QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (chronic graft-versus-host disease [cGVHD] progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1: itacitinib 300 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg QD + CS for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 300 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 400 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 400 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 300 mg BID + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg twice daily (BID) + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). The itacitanib dose could have been decreased to 200 mg BID if a boundary was reached during safety run-in. This treatment group was discontinued due to concern of a potential increase in relapse rate. Participants in this treatment group who were ongoing were allowed to reduce to 400 mg QD plus CS. Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: CS monotherapy
    Reporting group description
    		 Participants were treated with CS alone. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group values
    		 Part 1: itacitinib 200 mg QD + CS Part 1: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy Total
    Number of subjects
    		 11 10 35 39 29 36 160
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0 0
        Adults (18-64 years)
    		 9 6 28 30 26 24 123
        From 65-84 years
    		 2 4 7 9 3 12 37
        85 years and over
    		 0 0 0 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.2 ( 7.07 ) 58.4 ( 15.08 ) 53.6 ( 14.01 ) 52.6 ( 13.79 ) 52.6 ( 12.86 ) 55.7 ( 13.32 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 3 3 17 16 14 19 72
        Male
    		 8 7 18 23 15 17 88
    Race, Customized
    Units: Subjects
        White/Caucasian
    		 11 8 31 36 27 34 147
        Black/African-American
    		 0 1 2 0 0 0 3
        Asian
    		 0 1 1 3 2 1 8
        Captured as "Other" in Database
    		 0 0 1 0 0 1 2
    Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 4 2 6 8 1 5 26
        Not Hispanic or Latino
    		 6 8 25 26 19 29 113
        Not Reported
    		 1 0 2 2 4 2 11
        Unknown
    		 0 0 2 1 1 0 4
        Captured as "Other" in Database
    		 0 0 0 2 4 0 6

    End points

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    End points reporting groups
    Reporting group title
    Part 1: itacitinib 200 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 200 milligrams (mg) once daily (QD) + corticosteroids (CS) for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mgh/kilogram (kg) QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (chronic graft-versus-host disease [cGVHD] progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1: itacitinib 300 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg QD + CS for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 300 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 400 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 400 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 300 mg BID + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg twice daily (BID) + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). The itacitanib dose could have been decreased to 200 mg BID if a boundary was reached during safety run-in. This treatment group was discontinued due to concern of a potential increase in relapse rate. Participants in this treatment group who were ongoing were allowed to reduce to 400 mg QD plus CS. Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: CS monotherapy
    Reporting group description
    		 Participants were treated with CS alone. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Subject analysis set title
    Parts 1 and 1 Expansion; PK Analysis: 100 mg QD + CS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    For toxicity management purposes and/or due to coadministration of strong CYP3A4 inhibitors, participants who received a starting dose of itacitinib 200 mg or 300 mg QD + CS in Part 1 and a starting dose of itacitinib 300 mg or 400 mg QD + CS in Part 1 Expansion had first or second dose reductions to itacitinib 100 mg QD + CS and/or dose interruptions.

    Subject analysis set title
    Parts 1 and 1 Expansion; PK Analysis: itacitinib 200 mg QD+CS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants were treated with a starting dose of oral itacitinib 200 mg QD + CS in Part 1 or had a dose reduction to oral itacitinib 200 mg QC + CS in Part 1 or Part 1 Expansion. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). For toxicity management purposes and/or due to coadministration of strong CYP3A4 inhibitors, participants who received a starting dose of itacitinib 300 mg QD + CS in Part 1 and a starting dose of itacitinib 300 mg or 400 mg QD + CS in Part 1 Expansion had first or second dose reductions to itacitinib 200 mg QD + CS and/or dose interruptions.

    Subject analysis set title
    Parts 1 and 1 Expansion; PK Analysis: itacitinib 300 mg QD+CS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants were treated with a starting dose of oral itacitinib 300 mg QD + CS in Part 1 or Part 1 Expansion or had a dose reduction to oral itacitinib 300 mg QC + CS in Part 1 Expansion. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (chronic graft-versus-host disease [cGVHD] progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months. For toxicity management purposes and/or due to coadministration of strong CYP3A4 inhibitors, participants who received a starting dose of itacitinib 400 mg QD + CS in Part 1 Expansion had a dose reduction to itacitinib 300 mg QD + CS and/or dose interruptions.

    Subject analysis set title
    Part 1 Expansion; PK Analysis: itacitinib 400 mg QD + CS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants were treated with oral itacitinib 400 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months. This group also included participants who originally received itacitinib 300 mg BID + CS but were ongoing at the time the 300 mg BID + CS treatment group was discontinued due to concern of a potential increase in relapse rate. At the time of discontinuation of the itacitinib 300 mg BID + CS treatment arm, participants reduced to itacitinib 400 mg QD + CS.

    Subject analysis set title
    Part 1 Expansion; PK Analysis: itacitinib 100 mg BID + CS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    For toxicity management purposes and/or due to coadministration of strong CYP3A4 inhibitors, participants who received a starting dose of itacitinib 300 mg BID + CS in Part 1 Expansion had first or second dose reductions to itacitinib 100 mg BID + CS and/or dose interruptions.

    Subject analysis set title
    Part 1 Expansion; PK Analysis: itacitinib 200 mg BID + CS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants were treated with a starting dose of oral itacitinib 300 mg BID + CS in Part 1 Expansion and had their dose decreased to itacitinib 200 mg BID + CS because a boundary was reached during safety run-in or for toxicity management purposes and/or due to coadministration of strong CYP3A4 inhibitors. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months. For toxicity management purposes and/or due to coadministration of strong CYP3A4 inhibitors, participants who received a starting dose of itacitinib 300 mg BID + CS in Part 1 Expansion had a dose reduction to itacitinib 200 mg BID + CS and/or dose interruptions.

    Subject analysis set title
    Part 1 Expansion; PK Analysis: itacitinib 300 mg BID + CS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Participants were treated with oral itacitinib 300 mg BID + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). The itacitanib dose could have been decreased to 200 mg BID if a boundary was reached during safety run-in. This treatment group was discontinued due to concern of a potential increase in relapse rate. Participants in this treatment group who were ongoing were allowed to reduce to 400 mg QD + CS. Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Primary: Part 1 Expansion: Number of participants with any treatment-emergent adverse event (TEAE)

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    End point title
    		 Part 1 Expansion: Number of participants with any treatment-emergent adverse event (TEAE) [1] [2]
    End point description
    An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
    End point type
    Primary
    End point timeframe
    until at least 30 days after the last dose of study treatment (up to 1103 days)
    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: Statistical analysis was not conducted for this endpoint.
    [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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    35
    39
    29
    36
    Units: participants
    34
    38
    28
    32
    No statistical analyses for this end point

    Primary: Part 1: Number of participants with dose-limiting toxicities (DLTs)

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    End point title
    		 Part 1: Number of participants with dose-limiting toxicities (DLTs) [3] [4]
    End point description
    A DLT was defined as the occurrence of any protocol-defined toxicity with onset up to and including Day 28, except those with a clear alternative explanation. Participants who received at least 21 of 28 doses of study drug at the level assigned or had a DLT were considered evaluable for determining tolerability of the dose. Participants who did not achieve this duration of exposure and did not have a DLT were to be replaced for purposes of toxicity identification.
    End point type
    Primary
    End point timeframe
    up to Day 28
    Notes
    [3] - 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: Statistical analysis was not conducted for this endpoint.
    [4] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1: itacitinib 200 mg QD + CS Part 1: itacitinib 300 mg QD + CS
    Number of subjects analysed
    11
    10
    Units: participants
    0
    1
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Response rate at Months 3 and 6

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    End point title
    		 Part 1 Expansion: Response rate at Months 3 and 6 [5]
    End point description
    Response rate was defined as the percentage of participants that had CR or PR, per NIH Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
    End point type
    Secondary
    End point timeframe
    Months 3 and 6
    Notes
    [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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    35
    39
    29
    36
    Units: percentage of participants
    number (confidence interval 95%)
        Month 3
    60.0 (42.1 to 76.1)
    69.2 (52.4 to 83.0)
    58.6 (38.9 to 76.5)
    50.0 (32.9 to 67.1)
        Month 6
    42.9 (26.3 to 60.6)
    53.8 (37.2 to 69.9)
    34.5 (17.9 to 54.3)
    36.1 (20.8 to 53.8)
    No statistical analyses for this end point

    Secondary: Parts 1 and 1 Expansion: Cmax of itacitinib

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    End point title
    		 Parts 1 and 1 Expansion: Cmax of itacitinib
    End point description
    Cmax was defined as the maximum observed concentration of itacitinib. 9999=SD cannot be reported for a single participant. 8888=Analysis was not conducted at this time point. Pharmacokinetic (PK) Evaluable Population: all participants who received at least 1 dose of study drug and/or reference therapy and provided at least 1 corresponding post-dose plasma sample (1 PK measurement). Because Part I and Part I Expansion were both randomized, open label, and had a parallel design with the same participant population criteria, as pre-specified, the PK data for identical doses/frequency of dosing were grouped for analysis (rather than conducting analysis by treatment arm).
    End point type
    Secondary
    End point timeframe
    Days 1, 7, and 28: predose and 1, 2, and 5 hours post-dose
    End point values
    		 Parts 1 and 1 Expansion; PK Analysis: 100 mg QD + CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 200 mg QD+CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 300 mg QD+CS Part 1 Expansion; PK Analysis: itacitinib 400 mg QD + CS Part 1 Expansion; PK Analysis: itacitinib 100 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 200 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 300 mg BID + CS
    Number of subjects analysed
    3 [6]
    27 [7]
    35 [8]
    26 [9]
    3 [10]
    14 [11]
    16 [12]
    Units: nanomoles per Liter (nmol/L)
    geometric mean (geometric coefficient of variation)
        Day 1, n=1, 23, 35, 26, 0, 12, 16
    201 ( 9999 )
    655 ( 82.9 )
    1050 ( 87.3 )
    951 ( 68.0 )
    8888 ( 8888 )
    769 ( 118 )
    736 ( 79.1 )
        Day 7, n=1, 27, 32, 26, 0 14, 12
    191 ( 9999 )
    1070 ( 88.9 )
    1580 ( 125 )
    1190 ( 103 )
    8888 ( 8888 )
    1520 ( 73.0 )
    1110 ( 66.2 )
        Day 28, n=3, 26, 27, 21, 3, 8, 10
    486 ( 140 )
    1460 ( 67.3 )
    1290 ( 248 )
    1350 ( 72.2 )
    1350 ( 29.4 )
    2040 ( 62.6 )
    1580 ( 51.4 )
    Notes
    [6] - PK Evaluable Population
    [7] - PK Evaluable Population
    [8] - PK Evaluable Population
    [9] - PK Evaluable Population
    [10] - PK Evaluable Population
    [11] - PK Evaluable Population
    [12] - PK Evaluable Population
    No statistical analyses for this end point

    Secondary: Parts 1 and 1 Expansion: Ctau (trough concentration of itacitinib over the dose interval) of itacitinib

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    End point title
    		 Parts 1 and 1 Expansion: Ctau (trough concentration of itacitinib over the dose interval) of itacitinib
    End point description
    9999=SD cannot be reported for a single participant. 8888=The absence of terminal PK measurements at baseline visits for the timepoint beyond 6 hours did not allow for precise and reasonable NCA estimates (as more than 3 PK data points are necessary beyond Cmax). 7777=The absence of terminal PK measurements at baseline visits for the timepoint beyond 6 hours did not allow for precise and reasonable NCA estimates (as more than 3 PK data points are necessary beyond Cmax). Of the total participants analyzed, only 1 participant had a PK profile that allowed for the NCA estimate of the parameter. The calculation of the SD was not possible. Because Part I and Part I Expansion were both randomized, open label, and had a parallel design with the same participant population criteria, as pre-specified, the PK data for identical doses/frequency of dosing were grouped for analysis (rather than conducting analysis by treatment arm).
    End point type
    Secondary
    End point timeframe
    Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
    End point values
    		 Parts 1 and 1 Expansion; PK Analysis: 100 mg QD + CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 200 mg QD+CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 300 mg QD+CS Part 1 Expansion; PK Analysis: itacitinib 400 mg QD + CS Part 1 Expansion; PK Analysis: itacitinib 100 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 200 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 300 mg BID + CS
    Number of subjects analysed
    3 [13]
    27 [14]
    35 [15]
    26 [16]
    3 [17]
    14 [18]
    16 [19]
    Units: nmol/L
    geometric mean (geometric coefficient of variation)
        Day 1, n=1, 23, 35, 26, 0, 12, 16
    8888 ( 8888 )
    8888 ( 8888 )
    0.153 ( 7777 )
    135 ( 197 )
    8888 ( 8888 )
    7.54 ( 7777 )
    8888 ( 8888 )
        Day 7, n=1, 27, 31, 24, 0, 14, 12
    0.298 ( 9999 )
    53.6 ( 218 )
    52.2 ( 425 )
    33.5 ( 118 )
    8888 ( 8888 )
    483 ( 175 )
    127 ( 177 )
        Day 28, n=3, 26, 26, 20, 3, 8, 10
    10.4 ( 4440 )
    68.0 ( 314 )
    42.2 ( 182 )
    29.7 ( 152 )
    392 ( 85.6 )
    460 ( 123 )
    195 ( 116 )
    Notes
    [13] - PK Evaluable Population
    [14] - PK Evaluable Population
    [15] - PK Evaluable Population
    [16] - PK Evaluable Population
    [17] - PK Evaluable Population
    [18] - PK Evaluable Population
    [19] - PK Evaluable Population
    No statistical analyses for this end point

    Secondary: Parts 1 and 1 Expansion: tmax (time to the maximum concentration of itacitinib) of itacitinib

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    End point title
    		 Parts 1 and 1 Expansion: tmax (time to the maximum concentration of itacitinib) of itacitinib
    End point description
    8888=Analysis was not conducted at this time point. Because Part I and Part I Expansion were both randomized, open label, and had a parallel design with the same participant population criteria, as pre-specified, the PK data for identical doses/frequency of dosing were grouped for analysis (rather than conducting analysis by treatment arm). For pharmacokinetic steady state Day 7 and Day 28, for the calculation of noncompartmental analysis exposure estimates (as more than 3 PK data points are necessary for the estimation beyond Cmax) it was assumed, that PK concentration returns to the predose value (at 12 hours post-dose for BID dosing; at 24 hours post-dose for QD dosing). Predose PK samples were transposed to 24 hours post-dose for QD administration and to 12 hours post-dose for BID administration to allow the steady-state NCA PK estimates on Day 7 and Day 28.
    End point type
    Secondary
    End point timeframe
    Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
    End point values
    		 Parts 1 and 1 Expansion; PK Analysis: 100 mg QD + CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 200 mg QD+CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 300 mg QD+CS Part 1 Expansion; PK Analysis: itacitinib 400 mg QD + CS Part 1 Expansion; PK Analysis: itacitinib 100 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 200 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 300 mg BID + CS
    Number of subjects analysed
    3 [20]
    27 [21]
    35 [22]
    26 [23]
    3 [24]
    14 [25]
    16 [26]
    Units: hours
    median (full range (min-max))
        Day 1, n=1, 23, 35, 26, 0, 12, 16
    1.0 (1.0 to 1.0)
    2.1 (0.9 to 4.8)
    2.1 (0.8 to 5.0)
    2.0 (0.0 to 5.0)
    8888 (8888 to 8888)
    2.0 (1.0 to 5.0)
    2.4 (1.0 to 5.0)
        Day 7, n=1, 27, 32, 26, 0, 14, 12
    1.0 (1.0 to 1.0)
    2.1 (0.0 to 5.0)
    2.0 (1.0 to 13.4)
    2.0 (1.0 to 5.2)
    8888 (8888 to 8888)
    1.9 (0.0 to 10.7)
    2.0 (0.9 to 5.0)
        Day 28, n=3, 26, 27, 21, 3, 8, 10
    4.0 (1.0 to 4.8)
    3.1 (0.8 to 12.0)
    2.0 (0.0 to 16.9)
    2.1 (0.9 to 5.0)
    2.0 (2.0 to 2.2)
    2.3 (2.0 to 5.6)
    2.0 (1.0 to 5.0)
    Notes
    [20] - PK Evaluable Population
    [21] - PK Evaluable Population
    [22] - PK Evaluable Population
    [23] - PK Evaluable Population
    [24] - PK Evaluable Population
    [25] - PK Evaluable Population
    [26] - PK Evaluable Population
    No statistical analyses for this end point

    Secondary: Parts 1 and 1 Expansion: Cl/F (apparent oral dose clearance of itacitinib) of itacitinib

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    End point title
    		 Parts 1 and 1 Expansion: Cl/F (apparent oral dose clearance of itacitinib) of itacitinib
    End point description
    9999=SD cannot be reported for a single participant. 8888=The absence of terminal PK measurements at baseline visits for the timepoint beyond 6 hours did not allow for precise and reasonable NCA estimates (as more than 3 PK data points are necessary beyond Cmax). 7777=The absence of terminal PK measurements at baseline visits for the timepoint beyond 6 hours did not allow for precise and reasonable NCA estimates (as more than 3 PK data points are necessary beyond Cmax). Of the total participants analyzed, only 1 participant had a PK profile that allowed for the noncompartmental analysis estimate of the parameter. The calculation of the SD was not possible. Because Part I and Part I Expansion were both randomized, open label, and had a parallel design with the same participant population criteria, as pre-specified, the PK data for identical doses/frequency of dosing were grouped for analysis (rather than conducting analysis by treatment arm).
    End point type
    Secondary
    End point timeframe
    Day 1: predose, and 1, 2, and 5 hours post-dose. Days 7 and 28: predose, and 1, 2, 5, 12 (for BID dosing), and 24 hours post-dose (for QD dosing)
    End point values
    		 Parts 1 and 1 Expansion; PK Analysis: 100 mg QD + CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 200 mg QD+CS Parts 1 and 1 Expansion; PK Analysis: itacitinib 300 mg QD+CS Part 1 Expansion; PK Analysis: itacitinib 400 mg QD + CS Part 1 Expansion; PK Analysis: itacitinib 100 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 200 mg BID + CS Part 1 Expansion; PK Analysis: itacitinib 300 mg BID + CS
    Number of subjects analysed
    3 [27]
    27 [28]
    35 [29]
    26 [30]
    3 [31]
    14 [32]
    16 [33]
    Units: Liters per hour
    geometric mean (geometric coefficient of variation)
        Day 1, n=1, 23, 35, 26, 0, 12, 16
    8888 ( 8888 )
    8888 ( 8888 )
    258 ( 7777 )
    41.2 ( 130 )
    8888 ( 8888 )
    640 ( 7777 )
    8888 ( 8888 )
        Day 7, n=1, 27, 31, 24, 0, 14, 12
    224 ( 9999 )
    43.0 ( 105 )
    48.9 ( 159 )
    85.9 ( 90.7 )
    8888 ( 8888 )
    31.8 ( 82.9 )
    94.4 ( 61.3 )
        Day 28, n=3, 26, 26, 20, 3, 8, 10
    47.7 ( 211 )
    30.0 ( 96.9 )
    54.8 ( 189 )
    81.0 ( 65.1 )
    20.2 ( 54.2 )
    26.9 ( 75.5 )
    67.5 ( 62.1 )
    Notes
    [27] - PK Evaluable Population
    [28] - PK Evaluable Population
    [29] - PK Evaluable Population
    [30] - PK Evaluable Population
    [31] - PK Evaluable Population
    [32] - PK Evaluable Population
    [33] - PK Evaluable Population
    No statistical analyses for this end point

    Secondary: Part 1: Response rate at Months 3, 6, and 12

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    End point title
    		 Part 1: Response rate at Months 3, 6, and 12 [34]
    End point description
    Response rate was defined as the percentage of participants that had CR or PR, per NIH Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
    End point type
    Secondary
    End point timeframe
    Months 3, 6, and 12
    Notes
    [34] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1: itacitinib 200 mg QD + CS Part 1: itacitinib 300 mg QD + CS
    Number of subjects analysed
    11
    10
    Units: percentage of participants
    number (confidence interval 95%)
        Month 3
    63.6 (30.8 to 89.1)
    50.0 (18.7 to 81.3)
        Month 6
    36.4 (10.9 to 69.2)
    50.0 (18.7 to 81.3)
        Month 12
    18.2 (2.3 to 51.8)
    20.0 (2.5 to 55.6)
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Response rate at Month 12

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    End point title
    		 Part 1 Expansion: Response rate at Month 12 [35]
    End point description
    Response rate was defined as the percentage of participants that had CR or PR, per NIH Consensus Criteria, as determined by the investigator, within 14 days of the post-Baseline visit date until new anti-GVHD therapy or overall response-progression or relapse/progression of underlying disease. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
    End point type
    Secondary
    End point timeframe
    Month 12
    Notes
    [35] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    35
    39
    29
    36
    Units: percentage of participants
        number (confidence interval 95%)
    22.9 (10.4 to 40.1)
    41.0 (25.6 to 57.9)
    24.1 (10.3 to 43.5)
    19.4 (8.2 to 36.0)
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Overall survival

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    End point title
    		 Part 1 Expansion: Overall survival [36]
    End point description
    Overall survival was defined as the interval between the date of randomization and the date of death due to any cause. -9999, 9999=the median and the upper and lower limits of the confidence interval were not estimable because too few participants died.
    End point type
    Secondary
    End point timeframe
    up to 36 months
    Notes
    [36] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    35
    39
    29
    36
    Units: days
        median (confidence interval 95%)
    9999 (694.0 to 9999)
    9999 (-9999 to 9999)
    9999 (-9999 to 9999)
    9999 (-9999 to 9999)
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Duration of response

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    End point title
    		 Part 1 Expansion: Duration of response [37]
    End point description
    Duration to response was defined as the interval between the first response and cGVHD progression, death, or the initiation of a new systemic cGVHD therapy. 9999=the median and the upper limit of the confidence interval were not estimable because too few participants had disease progression or died or initiated new systemic cGVHD therapy.
    End point type
    Secondary
    End point timeframe
    up to 24 months
    Notes
    [37] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    31
    31
    25
    26
    Units: days
        median (confidence interval 95%)
    581.0 (147.0 to 807.0)
    9999 (306.0 to 9999)
    512.0 (161.0 to 9999)
    197.0 (103.0 to 9999)
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Time to response

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    End point title
    		 Part 1 Expansion: Time to response [38]
    End point description
    Time to response was defined as the interval between randomization and the first response (CR or PR) before initiation of new therapy. CR was defined as the complete resolution of all signs and symptoms of cGvHD in all evaluable organs. PR was defined as an improvement in at least one organ without progression in other organs.
    End point type
    Secondary
    End point timeframe
    up to Month 12
    Notes
    [38] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    31
    31
    25
    26
    Units: days
        median (full range (min-max))
    16.0 (12 to 120)
    16.0 (12 to 86)
    16.0 (13 to 145)
    16.0 (13 to 88)
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Percentage of participants successfully tapered off all corticosteroids at Day 180

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    End point title
    		 Part 1 Expansion: Percentage of participants successfully tapered off all corticosteroids at Day 180 [39]
    End point description
    The percentage of participants who were not taking any corticosteroids at Day 180 was assessed.
    End point type
    Secondary
    End point timeframe
    Day 180
    Notes
    [39] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    21
    27
    17
    18
    Units: percentage of participants
        number (not applicable)
    52.4
    66.7
    47.1
    44.4
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Percentage of participants with a ≥50% reduction in daily corticosteroid dose at Day 180 from the corticosteroid dose on Day 1

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    End point title
    		 Part 1 Expansion: Percentage of participants with a ≥50% reduction in daily corticosteroid dose at Day 180 from the corticosteroid dose on Day 1 [40]
    End point description
    The corticosteroid dose at Day 180 was compared to the corticosteroid dose on Day 1 to assess reduction.
    End point type
    Secondary
    End point timeframe
    Day 1; Day 180
    Notes
    [40] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    21
    27
    17
    18
    Units: percentage of participants
        number (not applicable)
    90.5
    100.0
    100.0
    100.0
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Nonrelapse mortality (NRM) rate

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    End point title
    		 Part 1 Expansion: Nonrelapse mortality (NRM) rate [41]
    End point description
    NRM was defined as the percentage of participants who died due to causes other than a relapse of their primary hematologic disease.
    End point type
    Secondary
    End point timeframe
    up to 24 months
    Notes
    [41] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    35
    37
    28
    35
    Units: percentage of participants
        number (confidence interval 95%)
    25.7 (12.5 to 43.3)
    15.4 (6.2 to 32.0)
    10.3 (2.3 to 28.2)
    11.1 (3.2 to 26.7)
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Relapse rate of malignant and nonmalignant hematologic diseases

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    End point title
    		 Part 1 Expansion: Relapse rate of malignant and nonmalignant hematologic diseases [42]
    End point description
    The relapse rate was defined as percentage of participants whose underlying disease relapsed at any time during the course of the study.
    End point type
    Secondary
    End point timeframe
    up to 1073 days
    Notes
    [42] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    35
    39
    29
    36
    Units: percentage of participants
        number (confidence interval 95%)
    5.7 (0.7 to 19.2)
    7.7 (1.6 to 20.9)
    13.8 (3.9 to 31.7)
    2.8 (0.1 to 14.5)
    No statistical analyses for this end point

    Secondary: Part 1 Expansion: Time to primary hematologic disease relapse

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    End point title
    		 Part 1 Expansion: Time to primary hematologic disease relapse [43]
    End point description
    Time to primary hematologic disease relapse was defined as the interval between the date of randomization and the date of relapse. -9999, 9999=Too few participants had an event of relapse for a meaningful median/95% confidence interval to be calculated; thus, the Kaplan-Meier estimator cannot provide a valid estimate. Analysis included censored participants. Censored participants didn’t have an event of relapse at any time up to the last assessment date. Participants who didn’t have an event of hematologic disease relapse were censored at the time of the last assessment.
    End point type
    Secondary
    End point timeframe
    up to 24 months
    Notes
    [43] - 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: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: CS monotherapy
    Number of subjects analysed
    35
    39
    29
    36
    Units: days
        median (confidence interval 95%)
    9999 (-9999 to 9999)
    9999 (-9999 to 9999)
    9999 (-9999 to 9999)
    9999 (-9999 to 9999)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    until at least 30 days after the last dose of study treatment (up to 1103 days)
    Adverse event reporting additional description
    TEAEs have been reported. As pre-specified in the SAP, the overall summary of AEs by treatment group included the number of participants with itacitinib dose reductions due to AEs or concomitant strong CYP3A4 inhibitors. The SAP defines “treatment groups” as those to which participants were originally randomized.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    Part 1: itacitinib 200 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 200 milligrams (mg) once daily (QD) + corticosteroids (CS) for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mg/kilogram (kg) QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (chronic graft-versus-host disease [cGVHD] progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1: itacitinib 300 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg QD + CS for a maximum of 36 months. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 300 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 400 mg QD + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 400 mg QD + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: itacitinib 300 mg BID + CS
    Reporting group description
    		 Participants were treated with oral itacitinib 300 mg twice daily (BID) + CS. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). The itacitanib dose could have been decreased to 200 mg BID if a boundary was reached during safety run-in. This treatment group was discontinued due to concern of a potential increase in relapse rate. Participants in this treatment group who were ongoing were allowed to reduce to 400 mg QD plus CS. Itacitinib treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Reporting group title
    Part 1 Expansion: Total
    Reporting group description
    		 Participants received 300 mg QD, 400 mg QD, or 300 mg BID itacitinib plus corticosteroids.

    Reporting group title
    Part 1 Expansion: CS monotherapy
    Reporting group description
    		 Participants were treated with CS alone. CS were given at a starting dose of 0.5 to 1.0 mg/kg QD (prednisone or methylprednisolone equivalent to prednisone dose). Treatment was to continue until treatment failure (cGVHD progression, death, or initiation of new systemic cGVHD therapy), unacceptable toxicity, or withdrawal of consent, for a maximum of 36 months.

    Serious adverse events
    		 Part 1: itacitinib 200 mg QD + CS Part 1: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: Total Part 1 Expansion: CS monotherapy
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 11 (54.55%)
    5 / 10 (50.00%)
    18 / 35 (51.43%)
    22 / 39 (56.41%)
    12 / 29 (41.38%)
    52 / 103 (50.49%)
    9 / 36 (25.00%)
         number of deaths (all causes)
    2
    3
    9
    8
    4
    21
    5
         number of deaths resulting from adverse events
    1
    1
    3
    4
    1
    8
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Small cell lung cancer
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic limb pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venoocclusive disease
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Catheter site inflammation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Physical deconditioning
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    4 / 39 (10.26%)
    0 / 29 (0.00%)
    4 / 103 (3.88%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    2 / 4
    0 / 0
    2 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis obliterans syndrome
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Dyspnoea
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric decompensation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood lactic acid increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    International normalised ratio increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SARS-CoV-2 test positive
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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 / 1
    Injury, poisoning and procedural complications
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Bundle branch block left
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Optic neuritis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Blindness unilateral
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal vein occlusion
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 4
    1 / 1
    0 / 0
    3 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Colitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    2 / 103 (1.94%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    1 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    2 / 36 (5.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    2 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic fibrosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Night sweats
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysuria
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pollakiuria
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Myositis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    3 / 39 (7.69%)
    2 / 29 (6.90%)
    6 / 103 (5.83%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 3
    0 / 2
    1 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 2
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridial sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection reactivation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis viral
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytomegalovirus oesophagitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis Escherichia coli
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster cutaneous disseminated
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Pneumonia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    5 / 39 (12.82%)
    2 / 29 (6.90%)
    9 / 103 (8.74%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    1 / 3
    2 / 5
    1 / 2
    4 / 10
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Pneumonia parainfluenzae viral
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonia cytomegaloviral
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    2 / 2
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    Pneumonia streptococcal
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Progressive multifocal leukoencephalopathy
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salmonella sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    1 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection enterococcal
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection viral
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Failure to thrive
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Food intolerance
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    1 / 36 (2.78%)
         occurrences causally related to treatment / all
    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
    Hypokalaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    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: itacitinib 200 mg QD + CS Part 1: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 300 mg QD + CS Part 1 Expansion: itacitinib 400 mg QD + CS Part 1 Expansion: itacitinib 300 mg BID + CS Part 1 Expansion: Total Part 1 Expansion: CS monotherapy
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 11 (100.00%)
    10 / 10 (100.00%)
    33 / 35 (94.29%)
    37 / 39 (94.87%)
    27 / 29 (93.10%)
    97 / 103 (94.17%)
    31 / 36 (86.11%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    3
    0
    Hot flush
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    3 / 29 (10.34%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    1
    3
    4
    0
    Hypertension
         subjects affected / exposed
    2 / 11 (18.18%)
    2 / 10 (20.00%)
    6 / 35 (17.14%)
    7 / 39 (17.95%)
    9 / 29 (31.03%)
    22 / 103 (21.36%)
    7 / 36 (19.44%)
         occurrences all number
    2
    3
    6
    8
    10
    24
    7
    Hypotension
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    3 / 35 (8.57%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    3
    0
    1
    4
    0
    Microangiopathy
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    4 / 35 (11.43%)
    1 / 39 (2.56%)
    2 / 29 (6.90%)
    7 / 103 (6.80%)
    2 / 36 (5.56%)
         occurrences all number
    1
    0
    5
    2
    2
    9
    2
    Chest discomfort
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    3
    0
    Fatigue
         subjects affected / exposed
    4 / 11 (36.36%)
    2 / 10 (20.00%)
    6 / 35 (17.14%)
    7 / 39 (17.95%)
    4 / 29 (13.79%)
    17 / 103 (16.50%)
    5 / 36 (13.89%)
         occurrences all number
    4
    3
    7
    8
    4
    19
    5
    Influenza like illness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    2 / 29 (6.90%)
    2 / 103 (1.94%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    5
    5
    1
    Oedema
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    2 / 29 (6.90%)
    4 / 103 (3.88%)
    1 / 36 (2.78%)
         occurrences all number
    2
    1
    1
    1
    2
    4
    1
    Oedema peripheral
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    6 / 35 (17.14%)
    5 / 39 (12.82%)
    6 / 29 (20.69%)
    17 / 103 (16.50%)
    6 / 36 (16.67%)
         occurrences all number
    2
    0
    6
    5
    7
    18
    6
    Pyrexia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    4 / 35 (11.43%)
    5 / 39 (12.82%)
    6 / 29 (20.69%)
    15 / 103 (14.56%)
    3 / 36 (8.33%)
         occurrences all number
    2
    1
    6
    6
    6
    18
    4
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    2
    0
    Reproductive system and breast disorders
    Breast pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Vulvovaginal dryness
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Vaginal discharge
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    4 / 39 (10.26%)
    2 / 29 (6.90%)
    6 / 103 (5.83%)
    3 / 36 (8.33%)
         occurrences all number
    0
    0
    0
    4
    2
    6
    4
    Dyspnoea
         subjects affected / exposed
    3 / 11 (27.27%)
    1 / 10 (10.00%)
    5 / 35 (14.29%)
    2 / 39 (5.13%)
    1 / 29 (3.45%)
    8 / 103 (7.77%)
    5 / 36 (13.89%)
         occurrences all number
    3
    1
    7
    2
    1
    10
    5
    Epistaxis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    3 / 29 (10.34%)
    5 / 103 (4.85%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    5
    7
    0
    Nasal congestion
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Oropharyngeal pain
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    2
    1
    0
    3
    0
    Productive cough
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    2
    0
    0
    2
    1
    Pulmonary oedema
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    2
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    2 / 39 (5.13%)
    1 / 29 (3.45%)
    4 / 103 (3.88%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    2
    1
    4
    1
    Confusional state
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    2 / 36 (5.56%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    2
    Insomnia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    3 / 35 (8.57%)
    8 / 39 (20.51%)
    4 / 29 (13.79%)
    15 / 103 (14.56%)
    5 / 36 (13.89%)
         occurrences all number
    1
    1
    3
    8
    5
    16
    5
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    5 / 35 (14.29%)
    6 / 39 (15.38%)
    6 / 29 (20.69%)
    17 / 103 (16.50%)
    0 / 36 (0.00%)
         occurrences all number
    0
    2
    7
    14
    10
    31
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    3 / 35 (8.57%)
    4 / 39 (10.26%)
    2 / 29 (6.90%)
    9 / 103 (8.74%)
    1 / 36 (2.78%)
         occurrences all number
    5
    0
    5
    6
    4
    15
    1
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    3
    1
    1
    1
    1
    3
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    2 / 39 (5.13%)
    1 / 29 (3.45%)
    4 / 103 (3.88%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    2
    1
    4
    1
    Blood cholesterol increased
         subjects affected / exposed
    3 / 11 (27.27%)
    2 / 10 (20.00%)
    3 / 35 (8.57%)
    4 / 39 (10.26%)
    4 / 29 (13.79%)
    11 / 103 (10.68%)
    1 / 36 (2.78%)
         occurrences all number
    3
    2
    3
    5
    4
    12
    2
    Blood creatinine increased
         subjects affected / exposed
    3 / 11 (27.27%)
    2 / 10 (20.00%)
    3 / 35 (8.57%)
    4 / 39 (10.26%)
    3 / 29 (10.34%)
    10 / 103 (9.71%)
    1 / 36 (2.78%)
         occurrences all number
    6
    2
    3
    7
    5
    15
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    1
    1
    3
    0
    Blood potassium decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    2 / 29 (6.90%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    0
    Blood potassium increased
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    1
    0
    0
    1
    0
    Blood sodium decreased
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    1
    0
    0
    1
    0
    Blood triglycerides increased
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    1 / 36 (2.78%)
         occurrences all number
    2
    1
    1
    0
    0
    1
    1
    Cytomegalovirus test positive
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    0
    Drug level increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    4 / 39 (10.26%)
    1 / 29 (3.45%)
    6 / 103 (5.83%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    6
    2
    9
    0
    Haemoglobin decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    3 / 35 (8.57%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    2
    3
    0
    0
    3
    0
    Haemoglobin increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Liver function test increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    4
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    4 / 39 (10.26%)
    0 / 29 (0.00%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    5
    0
    5
    0
    Platelet count decreased
         subjects affected / exposed
    5 / 11 (45.45%)
    3 / 10 (30.00%)
    6 / 35 (17.14%)
    7 / 39 (17.95%)
    9 / 29 (31.03%)
    22 / 103 (21.36%)
    2 / 36 (5.56%)
         occurrences all number
    5
    3
    6
    7
    11
    24
    2
    Weight increased
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    3
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    2
    1
    1
    4
    0
    Fall
         subjects affected / exposed
    3 / 11 (27.27%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    2 / 29 (6.90%)
    4 / 103 (3.88%)
    3 / 36 (8.33%)
         occurrences all number
    3
    1
    3
    2
    2
    7
    3
    Limb injury
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Tooth fracture
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Wound
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    2
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    3 / 35 (8.57%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    5 / 103 (4.85%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    3
    2
    0
    5
    0
    Bradycardia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Cardiac failure
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    4 / 35 (11.43%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    6 / 103 (5.83%)
    2 / 36 (5.56%)
         occurrences all number
    0
    0
    5
    1
    1
    7
    2
    Nervous system disorders
    Balance disorder
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    3 / 35 (8.57%)
    2 / 39 (5.13%)
    2 / 29 (6.90%)
    7 / 103 (6.80%)
    2 / 36 (5.56%)
         occurrences all number
    0
    1
    3
    2
    2
    7
    2
    Dysgeusia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    3 / 39 (7.69%)
    0 / 29 (0.00%)
    5 / 103 (4.85%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    2
    3
    0
    5
    1
    Headache
         subjects affected / exposed
    2 / 11 (18.18%)
    2 / 10 (20.00%)
    2 / 35 (5.71%)
    6 / 39 (15.38%)
    1 / 29 (3.45%)
    9 / 103 (8.74%)
    3 / 36 (8.33%)
         occurrences all number
    2
    2
    2
    6
    1
    9
    4
    Hypoaesthesia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    2
    0
    0
    2
    1
    Paraesthesia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    2
    0
    Sciatica
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    1
    Presyncope
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Polyneuropathy
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    2
    0
    0
    2
    1
    Tremor
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    2 / 29 (6.90%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    0
    2
    4
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 11 (27.27%)
    2 / 10 (20.00%)
    14 / 35 (40.00%)
    9 / 39 (23.08%)
    10 / 29 (34.48%)
    33 / 103 (32.04%)
    1 / 36 (2.78%)
         occurrences all number
    4
    2
    18
    13
    12
    43
    1
    Febrile neutropenia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    Haemolysis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Leukopenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    3 / 35 (8.57%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    3
    0
    Lymphopenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    4
    1
    0
    5
    0
    Neutropenia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    5 / 35 (14.29%)
    3 / 39 (7.69%)
    3 / 29 (10.34%)
    11 / 103 (10.68%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    8
    11
    6
    25
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 10 (20.00%)
    8 / 35 (22.86%)
    7 / 39 (17.95%)
    5 / 29 (17.24%)
    20 / 103 (19.42%)
    1 / 36 (2.78%)
         occurrences all number
    2
    2
    9
    8
    5
    22
    1
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    2 / 29 (6.90%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    0
    Cataract
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    Cataract nuclear
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Dry eye
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    3 / 39 (7.69%)
    2 / 29 (6.90%)
    6 / 103 (5.83%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    4
    2
    7
    0
    Lacrimation increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    2 / 39 (5.13%)
    2 / 29 (6.90%)
    6 / 103 (5.83%)
    2 / 36 (5.56%)
         occurrences all number
    0
    1
    2
    2
    2
    6
    2
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    2 / 29 (6.90%)
    5 / 103 (4.85%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    2
    1
    2
    5
    1
    Abdominal pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    3 / 35 (8.57%)
    3 / 39 (7.69%)
    1 / 29 (3.45%)
    7 / 103 (6.80%)
    2 / 36 (5.56%)
         occurrences all number
    1
    0
    3
    3
    2
    8
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    6 / 35 (17.14%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    7 / 103 (6.80%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    6
    0
    1
    7
    0
    Anal fissure
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    4 / 35 (11.43%)
    7 / 39 (17.95%)
    2 / 29 (6.90%)
    13 / 103 (12.62%)
    2 / 36 (5.56%)
         occurrences all number
    0
    1
    4
    7
    2
    13
    2
    Dry mouth
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    3 / 35 (8.57%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    3
    4
    1
    0
    5
    0
    Diarrhoea
         subjects affected / exposed
    1 / 11 (9.09%)
    4 / 10 (40.00%)
    6 / 35 (17.14%)
    4 / 39 (10.26%)
    6 / 29 (20.69%)
    16 / 103 (15.53%)
    5 / 36 (13.89%)
         occurrences all number
    1
    5
    6
    6
    9
    21
    5
    Dyspepsia
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    3 / 35 (8.57%)
    1 / 39 (2.56%)
    2 / 29 (6.90%)
    6 / 103 (5.83%)
    1 / 36 (2.78%)
         occurrences all number
    0
    2
    3
    2
    2
    7
    1
    Dysphagia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    3
    0
    Flatulence
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    3
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    Nausea
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    8 / 35 (22.86%)
    5 / 39 (12.82%)
    2 / 29 (6.90%)
    15 / 103 (14.56%)
    3 / 36 (8.33%)
         occurrences all number
    1
    1
    10
    6
    2
    18
    3
    Paraesthesia oral
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    4 / 35 (11.43%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    5 / 103 (4.85%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    6
    2
    0
    8
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    2
    0
    Dermatitis atopic
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dermatitis contact
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 10 (30.00%)
    3 / 35 (8.57%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    5 / 103 (4.85%)
    0 / 36 (0.00%)
         occurrences all number
    0
    3
    3
    2
    0
    5
    0
    Nail ridging
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    1
    1
    3
    0
    Rash
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    3 / 39 (7.69%)
    0 / 29 (0.00%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    4
    0
    5
    0
    Skin exfoliation
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    3 / 35 (8.57%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    2
    3
    0
    1
    4
    0
    Haematuria
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    3 / 39 (7.69%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    0
    4
    0
    4
    1
    Renal failure
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    0
    1
    2
    3
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    1
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    3
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    3 / 35 (8.57%)
    3 / 39 (7.69%)
    3 / 29 (10.34%)
    9 / 103 (8.74%)
    0 / 36 (0.00%)
         occurrences all number
    2
    1
    3
    4
    4
    11
    0
    Back pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    3 / 39 (7.69%)
    2 / 29 (6.90%)
    7 / 103 (6.80%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    2
    3
    2
    7
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    3 / 39 (7.69%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    3
    0
    3
    0
    Muscle spasms
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    4 / 29 (13.79%)
    6 / 103 (5.83%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    2
    4
    6
    1
    Muscular weakness
         subjects affected / exposed
    3 / 11 (27.27%)
    4 / 10 (40.00%)
    5 / 35 (14.29%)
    4 / 39 (10.26%)
    0 / 29 (0.00%)
    9 / 103 (8.74%)
    1 / 36 (2.78%)
         occurrences all number
    3
    4
    5
    4
    0
    9
    1
    Neck pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    2
    0
    Osteonecrosis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    1
    1
    0
    Osteoporosis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    2
    0
    Pain in extremity
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    2 / 29 (6.90%)
    3 / 103 (2.91%)
    2 / 36 (5.56%)
         occurrences all number
    2
    0
    0
    2
    2
    4
    2
    Tendon pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    1
    Infections and infestations
    Bronchiolitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Bronchitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    3 / 35 (8.57%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    2 / 36 (5.56%)
         occurrences all number
    0
    1
    3
    0
    0
    3
    2
    COVID-19
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    4 / 35 (11.43%)
    6 / 39 (15.38%)
    4 / 29 (13.79%)
    14 / 103 (13.59%)
    5 / 36 (13.89%)
         occurrences all number
    0
    0
    4
    6
    4
    14
    5
    Conjunctivitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    3 / 36 (8.33%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    3
    Cytomegalovirus viraemia
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    5 / 39 (12.82%)
    3 / 29 (10.34%)
    9 / 103 (8.74%)
    0 / 36 (0.00%)
         occurrences all number
    2
    0
    1
    5
    4
    10
    0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    3
    0
    1
    4
    0
    Cytomegalovirus infection reactivation
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 10 (10.00%)
    3 / 35 (8.57%)
    8 / 39 (20.51%)
    4 / 29 (13.79%)
    15 / 103 (14.56%)
    3 / 36 (8.33%)
         occurrences all number
    2
    1
    6
    14
    5
    25
    6
    Device related infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    2
    0
    Epstein-Barr virus infection reactivation
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    3 / 35 (8.57%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    4 / 103 (3.88%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    3
    3
    0
    6
    1
    Hordeolum
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Herpes zoster
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    2
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    3
    1
    4
    0
    Pneumonia viral
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    3 / 39 (7.69%)
    1 / 29 (3.45%)
    5 / 103 (4.85%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    1
    3
    1
    5
    0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    1
    Paronychia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 10 (20.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    0
    2
    0
    2
    0
    2
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    3 / 35 (8.57%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    4 / 103 (3.88%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    3
    0
    2
    5
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    3 / 39 (7.69%)
    1 / 29 (3.45%)
    5 / 103 (4.85%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    3
    3
    1
    7
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    2 / 29 (6.90%)
    2 / 103 (1.94%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    0
    0
    2
    2
    1
    Skin infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    1 / 29 (3.45%)
    4 / 103 (3.88%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    2
    1
    1
    4
    1
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    1 / 103 (0.97%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    1
    0
    Urinary tract infection enterococcal
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    0 / 35 (0.00%)
    2 / 39 (5.13%)
    1 / 29 (3.45%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    0
    2
    1
    3
    0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    0 / 36 (0.00%)
         occurrences all number
    1
    1
    2
    2
    0
    4
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    4 / 35 (11.43%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    5 / 103 (4.85%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    4
    1
    0
    5
    0
    Dehydration
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    1 / 29 (3.45%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    2
    0
    Fluid retention
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    0 / 35 (0.00%)
    0 / 39 (0.00%)
    0 / 29 (0.00%)
    0 / 103 (0.00%)
    0 / 36 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    3 / 39 (7.69%)
    1 / 29 (3.45%)
    5 / 103 (4.85%)
    1 / 36 (2.78%)
         occurrences all number
    1
    0
    1
    3
    1
    5
    1
    Hyperglycaemia
         subjects affected / exposed
    3 / 11 (27.27%)
    0 / 10 (0.00%)
    4 / 35 (11.43%)
    5 / 39 (12.82%)
    4 / 29 (13.79%)
    13 / 103 (12.62%)
    2 / 36 (5.56%)
         occurrences all number
    3
    0
    4
    5
    5
    14
    2
    Hyperkalaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    3 / 103 (2.91%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    3
    2
    0
    5
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    8 / 39 (20.51%)
    3 / 29 (10.34%)
    13 / 103 (12.62%)
    3 / 36 (8.33%)
         occurrences all number
    1
    1
    2
    9
    3
    14
    3
    Hypocalcaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    4 / 35 (11.43%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    5 / 103 (4.85%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    4
    3
    0
    7
    1
    Hypomagnesaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    5 / 35 (14.29%)
    2 / 39 (5.13%)
    1 / 29 (3.45%)
    8 / 103 (7.77%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    9
    6
    3
    18
    1
    Hyponatraemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    5 / 35 (14.29%)
    3 / 39 (7.69%)
    3 / 29 (10.34%)
    11 / 103 (10.68%)
    1 / 36 (2.78%)
         occurrences all number
    0
    1
    8
    5
    4
    17
    1
    Hypophosphataemia
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    2 / 35 (5.71%)
    1 / 39 (2.56%)
    2 / 29 (6.90%)
    5 / 103 (4.85%)
    0 / 36 (0.00%)
         occurrences all number
    0
    0
    2
    3
    2
    7
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 10 (10.00%)
    2 / 35 (5.71%)
    4 / 39 (10.26%)
    6 / 29 (20.69%)
    12 / 103 (11.65%)
    2 / 36 (5.56%)
         occurrences all number
    0
    1
    2
    6
    8
    16
    2
    Steroid diabetes
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    0 / 39 (0.00%)
    2 / 29 (6.90%)
    3 / 103 (2.91%)
    1 / 36 (2.78%)
         occurrences all number
    0
    0
    1
    0
    2
    3
    1
    Vitamin D deficiency
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 10 (0.00%)
    1 / 35 (2.86%)
    1 / 39 (2.56%)
    0 / 29 (0.00%)
    2 / 103 (1.94%)
    0 / 36 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Aug 2018
    The primary purpose of this amendment was to respond to Regulatory Authority feedback.
    02 Nov 2018
    The primary purpose of this amendment was to respond to Voluntary Harmonisation Procedure (VHP).
    30 Nov 2018
    The primary purpose of this amendment was to respond to VHP.
    07 Jun 2019
    The primary purpose of this amendment was to update and clarify exclusion criteria, the definition for treatment failure, dose-limiting toxicity (DLT) criteria, treatment of overdose, and maximum duration of study treatment, as well as to respond to health authorities.
    30 Aug 2019
    The primary purpose of this amendment was to ensure consistency between sections of the Protocol describing the reasons for discontinuation in response to VHP request.
    16 Dec 2019
    The primary purpose of this amendment was to specify the dose for Part 2 based on the analysis of data from Part 1 of the study, to update the dose modification and interruption guidelines, and to provide clarification in several areas of the Protocol.
    03 Apr 2020
    The primary purpose of this amendment was for the addition of a Part 1 Expansion part of the study and to update inclusion criteria, dose reduction scheme for concomitant medications, and itacitinib taper.
    30 Sep 2021
    The primary purpose of this amendment was for the discontinuation of Treatment Group C in the Part 1 Expansion part of the study and to update risk/benefit information, the dose reduction scheme for concomitant medications, and the frequency of pulmonary function tests in graft-versus-host disease (GVHD) follow-up.

    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.
    Based on Part 1 expansion preliminary efficacy data, Part 2 did not enroll participants. Part 1 Expansion participants who were tolerating and continuing to receive benefit from itacitinib could continue itacitinib treatment in study INCB 39110-801.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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