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    Clinical Trial Results:
    A Multi-Center, Phase 2, Open-label, Parallel Cohort Study of Efficacy and Safety of Duvelisib in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)

    Summary
    EudraCT number
    		 2019-001123-13
    Trial protocol
    		 DE   GB   IT  
    Global end of trial date
    22 Dec 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    20 Apr 2025
    First version publication date
    04 Jan 2025
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    • Correction of full data set
    Updated to align with another database.

    Trial information

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    Trial identification
    Sponsor protocol code
    VS-0145-225
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03372057
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Secura Bio, Inc.
    Sponsor organisation address
    1995 Village Center Circle, Suite 128, Las Vegas, NV, United States, 89134
    Public contact
    Ohad Bentur, MD, MHA, MSc/Senior Medical Director, Secura Bio, Inc., 1 702-254-0011, obentur@securabio.com
    Scientific contact
    Ohad Bentur, MD, MHA, MSc/Senior Medical Director, Secura Bio, Inc., 1 702-254-0011, obentur@securabio.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
    22 Dec 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Dec 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Dose Optimization Phase: To determine the optimal duvelisib dose for utilization in the Expansion Phase by evaluating the ORR supported by safety, additional efficacy, and pharmacokinetics parameters as well as any other available data in the population of participants receiving the optimal dose of duvelisib for at least one cycle in participants with relapsed or refractory PTCL. Expansion Phase: To determine the efficacy of the optimal dose of duvelisib in participants with relapsed or refractory PTCL.
    Protection of trial subjects
    This study was conducted in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which the study was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 May 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    United States: 117
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Italy: 21
    Country: Number of subjects enrolled
    Japan: 10
    Worldwide total number of subjects
    156
    EEA total number of subjects
    23
    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)
    70
    From 65 to 84 years
    83
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Regardless of study phase, all participants underwent screening assessments up to 30 days before the first study drug dose.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Dose Optimization Phase: Cohort 1
    Arm description
    		 Duvelisib was administered orally (PO) twice daily (BID) at a starting dose of 25 milligrams (mg), with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant’s response to and tolerance of therapy, in 28-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Duvelisib
    Investigational medicinal product code
    Other name
    IPI-145
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Duvelisib PO 25 mg BID or 50 mg BID or 75 mg BID in 28-day cycles.

    Arm title
    		 Dose Optimization Phase: Cohort 2
    Arm description
    		 Duvelisib 75 mg PO BID was administered in 28-day cycles.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Duvelisib
    Investigational medicinal product code
    Other name
    IPI-145
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Duvelisib PO 75 mg BID in 28-day cycles.

    Arm title
    		 Expansion Phase
    Arm description
    		 Duvelisib PO BID at a starting dose of 75 mg was administered for the first 2 cycles (28-day cycles), followed by a mandatory reduction to 25 mg BID thereafter for those participants with complete response (CR), partial response (PR) or stable disease (SD), in 28-day cycles (dose determined in Optimization Phase).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Duvelisib
    Investigational medicinal product code
    Other name
    IPI-145
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Duvelisib PO BID in 28-day cycles (dose determined in Optimization Phase).

    Number of subjects in period 1
    		Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2 Expansion Phase
    Started
    20
    13
    123
    Received at Least 1 Dose of Study Drug
    20
    13
    123
    Completed
    0
    0
    0
    Not completed
    20
    13
    123
         Consent withdrawn by subject
    1
    1
    4
         Adverse event, non-fatal
    -
    -
    1
         Death
    16
    11
    78
         Progressive Disease
    -
    -
    1
         Closure Of The Study By The Sponsor
    3
    1
    39

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Dose Optimization Phase: Cohort 1
    Reporting group description
    		 Duvelisib was administered orally (PO) twice daily (BID) at a starting dose of 25 milligrams (mg), with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant’s response to and tolerance of therapy, in 28-day cycles.

    Reporting group title
    Dose Optimization Phase: Cohort 2
    Reporting group description
    		 Duvelisib 75 mg PO BID was administered in 28-day cycles.

    Reporting group title
    Expansion Phase
    Reporting group description
    		 Duvelisib PO BID at a starting dose of 75 mg was administered for the first 2 cycles (28-day cycles), followed by a mandatory reduction to 25 mg BID thereafter for those participants with complete response (CR), partial response (PR) or stable disease (SD), in 28-day cycles (dose determined in Optimization Phase).

    Reporting group values
    		 Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2 Expansion Phase Total
    Number of subjects
    		 20 13 123 156
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.0 ( 14.81 ) 65.0 ( 7.22 ) 62.9 ( 13.59 ) -
    Gender categorical
    Units: Subjects
        Female
    		 6 4 56 66
        Male
    		 14 9 67 90
    Ethnicity (NIH/OMB)
    National Institutes of Health/Office of Management and Budget (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 2 0 12 14
        Not Hispanic or Latino
    		 18 12 111 141
        Unknown or Not Reported
    		 0 1 0 1
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 1 1 18 20
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        Black or African American
    		 2 0 9 11
        White
    		 16 12 92 120
        More than one race
    		 0 0 0 0
        Unknown or Not Reported
    		 1 0 4 5
    Eastern Cooperative Oncology Group (ECOG) Performance Status
    ECOG Performance Status is a scale that measures how cancer affects a participant’s’ daily living abilities. The scale ranges from 0 (fully active) to 5 (dead). 0 = fully active without restriction; 1 = Restricted in physically strenuous activity; 2 = Ambulatory, capable of all selfcare; 3 = Capable of limited selfcare; 4 = Completely disabled; 5 = Dead.
    Units: Subjects
        Status - 0
    		 8 5 49 62
        Status - 1
    		 8 7 64 79
        Status - 2
    		 3 1 10 14
        Status - 3
    		 0 0 0 0
        Status - 4
    		 0 0 0 0
        Status - 5
    		 0 0 0 0
        Missing
    		 1 0 0 1

    End points

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    End points reporting groups
    Reporting group title
    Dose Optimization Phase: Cohort 1
    Reporting group description
    		 Duvelisib was administered orally (PO) twice daily (BID) at a starting dose of 25 milligrams (mg), with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant’s response to and tolerance of therapy, in 28-day cycles.

    Reporting group title
    Dose Optimization Phase: Cohort 2
    Reporting group description
    		 Duvelisib 75 mg PO BID was administered in 28-day cycles.

    Reporting group title
    Expansion Phase
    Reporting group description
    		 Duvelisib PO BID at a starting dose of 75 mg was administered for the first 2 cycles (28-day cycles), followed by a mandatory reduction to 25 mg BID thereafter for those participants with complete response (CR), partial response (PR) or stable disease (SD), in 28-day cycles (dose determined in Optimization Phase).

    Subject analysis set title
    Dose Optimization Efficacy Set
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants who received at least one dose of study drug, completed at least one cycle of treatment, and have at least one scan to assess disease response after completion of one cycle of treatment.

    Subject analysis set title
    Modified Intent-to-treat (mITT)
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    All participants who receive at least one dose of study drug.

    Subject analysis set title
    All Participants
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Every study participant that received at least 1 dose of study drug and had evaluable data.

    Subject analysis set title
    Safety Analysis Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All participants who receive at least one dose of study drug.

    Primary: Overall Response Rate (ORR) as Assessed by the Investigator Using the Lugano Criteria

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    End point title
    		 Overall Response Rate (ORR) as Assessed by the Investigator Using the Lugano Criteria [1] [2]
    End point description
    ORR was defined as the percentage of participants with complete response (CR) + partial response (PR), as assessed by the investigator using the Lugano criteria, for participants receiving the optimal dose of duvelisib for at least one cycle of study therapy. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point.
    End point type
    Primary
    End point timeframe
    56 days (2 cycles; 28-day cycles)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics (percentage of participants plus confidence interval) are reported for this primary end point, as prespecified in the statistical analysis plan.
    [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: As pre-specified, efficacy analysis using investigator assessment reported for the Dose Optimization Phase only.
    End point values
    		 Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2
    Number of subjects analysed
    13 [3]
    13 [4]
    Units: percentage of participants
        number (confidence interval 95%)
    53.8 (26.7 to 80.9)
    53.8 (26.7 to 80.9)
    Notes
    [3] - Dose Optimization Efficacy Set
    [4] - Dose Optimization Efficacy Set
    No statistical analyses for this end point

    Primary: ORR as Assessed by the Independent Review Committee (IRC) Using the Lugano Criteria

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    End point title
    		 ORR as Assessed by the Independent Review Committee (IRC) Using the Lugano Criteria [5] [6]
    End point description
    ORR was defined as the percentage of participants with CR + PR, as assessed by the IRC using the Lugano criteria, for participants receiving the optimal dose of duvelisib for at least one cycle of study therapy. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point.
    End point type
    Primary
    End point timeframe
    56 days (2 cycles; 28-day cycles)
    Notes
    [5] - 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: As pre-specified, efficacy analysis using IRC assessment reported for the Expansion Phase only.
    [6] - 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: Only descriptive statistics (percentage of participants plus confidence interval) are reported for this primary end point, as prespecified in the statistical analysis plan.
    End point values
    		 Expansion Phase
    Number of subjects analysed
    123 [7]
    Units: percentage of participants
        number (confidence interval 95%)
    48.0 (39.1 to 56.8)
    Notes
    [7] - Modified Intent-to-treat (mITT)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) as Assessed by the Investigator Using the Lugano Criteria

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    End point title
    		 Duration of Response (DOR) as Assessed by the Investigator Using the Lugano Criteria [8]
    End point description
    DOR was defined for participants with CR or PR as the time from the date of the first documentation of response (CR or PR) to the date of the first documentation of progressive disease (PD) or death due to any cause. Participants who withdrew from the study for any reason prior to PD and participants who had ongoing response at the time of the data cut were censored at the date of their last response assessment. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point. '9999' = Insufficient number of participants with events to calculate upper confidence intervals.
    End point type
    Secondary
    End point timeframe
    Up to 70 months
    Notes
    [8] - 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: As pre-specified, efficacy analysis using investigator assessment reported for the Dose Optimization Phase only.
    End point values
    		 Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2
    Number of subjects analysed
    5 [9]
    5 [10]
    Units: month
        median (confidence interval 95%)
    4.22 (1.87 to 9999)
    3.32 (1.77 to 9999)
    Notes
    [9] - Dose Optimization Efficacy Set
    [10] - Dose Optimization Efficacy Set
    No statistical analyses for this end point

    Secondary: Progression-free Survival (PFS) as Assessed by the Investigator Using the Lugano Criteria

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    End point title
    		 Progression-free Survival (PFS) as Assessed by the Investigator Using the Lugano Criteria [11]
    End point description
    PFS was defined as the time from the date of first treatment to the date of the first radiographic disease progression or death due to any cause, whichever occurred first. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    Up to 70 months
    Notes
    [11] - 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: As pre-specified, efficacy analysis using investigator assessment reported for the Dose Optimization Phase only.
    End point values
    		 Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2
    Number of subjects analysed
    10 [12]
    11 [13]
    Units: month
        median (confidence interval 95%)
    3.55 (1.05 to 8.54)
    3.55 (1.81 to 13.14)
    Notes
    [12] - Dose Optimization Efficacy Set
    [13] - Dose Optimization Efficacy Set
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR) as Assessed by the Investigator Using the Lugano Criteria

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    End point title
    		 Disease Control Rate (DCR) as Assessed by the Investigator Using the Lugano Criteria [14]
    End point description
    DCR was defined as the percentage of participants with a best overall response of CR or PR or with a best overall response of stable disease (SD) sustained for at least 8 weeks. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    Up to 8 weeks
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified, efficacy analysis using investigator assessment reported for the Dose Optimization Phase only.
    End point values
    		 Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2
    Number of subjects analysed
    13 [15]
    13 [16]
    Units: percentage of participants
        median (confidence interval 95%)
    61.5 (35.1 to 88.0)
    61.5 (35.1 to 88.0)
    Notes
    [15] - Dose Optimization Efficacy Set
    [16] - Dose Optimization Efficacy Set
    No statistical analyses for this end point

    Secondary: DOR as Assessed by the IRC Using the Lugano Criteria

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    End point title
    		 DOR as Assessed by the IRC Using the Lugano Criteria [17]
    End point description
    DOR was defined for participants with CR or PR as the time from the date of the first documentation of response (CR or PR) to the date of the first documentation of progressive disease or death due to any cause. Participants who withdrew from the study for any reason prior to PD and participants who had ongoing response at the time of the data cut were censored at the date of their last response assessment. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    Up to 70 months
    Notes
    [17] - 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: As pre-specified, efficacy analysis using IRC assessment reported for the Expansion Phase only.
    End point values
    		 Expansion Phase
    Number of subjects analysed
    25 [18]
    Units: month
        median (confidence interval 95%)
    7.9 (6.4 to 21.00)
    Notes
    [18] - Modified Intent-to-treat (mITT)
    No statistical analyses for this end point

    Secondary: PFS as Assessed by the IRC Using the Lugano Criteria

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    End point title
    		 PFS as Assessed by the IRC Using the Lugano Criteria [19]
    End point description
    PFS was defined as the time from the date of first treatment to the date of the first radiographic disease progression or death due to any cause, whichever occurred first. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    Up to 70 months
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified, efficacy analysis using IRC assessment reported for the Expansion Phase only.
    End point values
    		 Expansion Phase
    Number of subjects analysed
    74 [20]
    Units: month
        median (confidence interval 95%)
    3.4 (1.8 to 3.9)
    Notes
    [20] - Modified Intent-to-treat (mITT)
    No statistical analyses for this end point

    Secondary: DCR as Assessed by the IRC Using the Lugano Criteria

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    End point title
    		 DCR as Assessed by the IRC Using the Lugano Criteria [21]
    End point description
    DCR was defined as the participants with a best overall response of CR or PR or with a best overall response of SD sustained for at least 8 weeks. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point.
    End point type
    Secondary
    End point timeframe
    Up to 8 weeks
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As pre-specified, efficacy analysis using IRC assessment reported for the Expansion Phase only.
    End point values
    		 Expansion Phase
    Number of subjects analysed
    123 [22]
    Units: percentage of participants
        number (confidence interval 95%)
    49.6 (40.8 to 58.4)
    Notes
    [22] - Modified Intent-to-treat (mITT)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS was defined as the time from the date of first treatment to the date of death due to any cause. Participants without documented death were censored at last alive date. Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point. '9999' = Insufficient number of participants with events to calculate the upper confidence interval.
    End point type
    Secondary
    End point timeframe
    Up to 70 months
    End point values
    		 Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2 Expansion Phase
    Number of subjects analysed
    9 [23]
    11 [24]
    78 [25]
    Units: month
        median (confidence interval 95%)
    6.70 (5.22 to 9999)
    10.58 (6.67 to 44.62)
    12.4 (8.4 to 22.7)
    Notes
    [23] - Dose Optimization Efficacy Set
    [24] - Dose Optimization Efficacy Set
    [25] - Modified Intent-to-treat (mITT)
    No statistical analyses for this end point

    Secondary: Plasma Concentration of IPI-145 (Duvelisib) and IPI-656 (Metabolite)

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    End point title
    		 Plasma Concentration of IPI-145 (Duvelisib) and IPI-656 (Metabolite)
    End point description
    Blood samples were taken for the analyses of duvelisib and IPI-656 in plasma at the designated time points. Results are reported as nanograms/millilitre (ng/mL). Here, ‘Number of subjects analysed’ signifies those participants who were evaluable for this end point. ‘9999’ = data not available due to no participants evaluable at the specified timepoint.
    End point type
    Secondary
    End point timeframe
    Day 15 of Cycles 1 and 2 (28-day cycles)
    End point values
    		 Dose Optimization Phase: Cohort 1 Dose Optimization Phase: Cohort 2 Expansion Phase
    Number of subjects analysed
    14 [26]
    12 [27]
    100 [28]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Duvelisib: Cycle 1, Day 15
    1238.1 ( 787.53 )
    2070.0 ( 889.39 )
    2873.7 ( 1709.15 )
        Duvelisib: Cycle 2, Day 15
    1492.5 ( 1019.10 )
    9999 ( 9999 )
    2648.2 ( 1336.94 )
        Metabolite (IPI-156): Cycle 1, Day 15
    1310.4 ( 1408.99 )
    1580.9 ( 772.13 )
    2387.5 ( 1919.33 )
        Metabolite (IPI-156): Cycle 2, Day 15
    894.8 ( 441.55 )
    9999 ( 9999 )
    2427.0 ( 1655.89 )
    Notes
    [26] - Safety Analysis Set; Cycle 1, Day 15: N=14; Cycle 2, Day 15: N=4
    [27] - Safety Analysis Set; Cycle 1, Day 15: N=12; Cycle 2, Day 15: N=0
    [28] - Safety Analysis Set; Cycle 1, Day 15: N=100; Cycle 2, Day 15: N=68
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From start of treatment (Day 1) to end of study (70 months).
    Adverse event reporting additional description
    All reported safety data based upon Safety Analysis Set: all participants who received at least one dose of study drug. All-cause mortality reported as occurrence of death due to any cause during the study and after study discontinuation.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24
    Reporting groups
    Reporting group title
    Dose Optimization Phase: Cohort 1
    Reporting group description
    		 Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-participant basis to 50 mg and then 75 mg, based on the participant’s response to and tolerance of therapy, in 28-day cycles.

    Reporting group title
    Expansion Phase
    Reporting group description
    		 Duvelisib PO BID at a starting dose of 75 mg for the first 2 cycles, followed by a mandatory reduction to 25 mg BID thereafter for those participants with CR, PR or SD, in 28-day cycles (dose determined in Optimization Phase).

    Reporting group title
    Dose Optimization Phase: Cohort 2
    Reporting group description
    		 Duvelisib 75 mg PO BID, administered in 28-day cycles.

    Serious adverse events
    		 Dose Optimization Phase: Cohort 1 Expansion Phase Dose Optimization Phase: Cohort 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 20 (70.00%)
    60 / 123 (48.78%)
    9 / 13 (69.23%)
         number of deaths (all causes)
    16
    78
    11
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Epstein-Barr virus associated lymphoproliferative disorder
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Post transplant lymphoproliferative disorder
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Allogenic stem cell transplantation
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    3 / 20 (15.00%)
    10 / 123 (8.13%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 10
    0 / 0
         deaths causally related to treatment / all
    0 / 3
    0 / 10
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 20 (5.00%)
    6 / 123 (4.88%)
    3 / 13 (23.08%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 6
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 20 (10.00%)
    3 / 123 (2.44%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 123 (2.44%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular dementia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 20 (5.00%)
    9 / 123 (7.32%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    1 / 1
    9 / 11
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Psoriasis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash morbilliform
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erythema
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eczema
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Synovial cyst
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bacteraemia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 20 (15.00%)
    3 / 123 (2.44%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 20 (20.00%)
    4 / 123 (3.25%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    4 / 6
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex viraemia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia cytomegaloviral
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective spondylitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cryptococcosis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Coronavirus infection
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic candida
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Dose Optimization Phase: Cohort 1 Expansion Phase Dose Optimization Phase: Cohort 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    19 / 20 (95.00%)
    120 / 123 (97.56%)
    13 / 13 (100.00%)
    Vascular disorders
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Hypertension
         subjects affected / exposed
    1 / 20 (5.00%)
    16 / 123 (13.01%)
    1 / 13 (7.69%)
         occurrences all number
    2
    27
    1
    Hypotension
         subjects affected / exposed
    3 / 20 (15.00%)
    12 / 123 (9.76%)
    2 / 13 (15.38%)
         occurrences all number
    4
    13
    2
    General disorders and administration site conditions
    Malaise
         subjects affected / exposed
    2 / 20 (10.00%)
    3 / 123 (2.44%)
    0 / 13 (0.00%)
         occurrences all number
    2
    4
    0
    Generalised oedema
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    Fatigue
         subjects affected / exposed
    7 / 20 (35.00%)
    38 / 123 (30.89%)
    6 / 13 (46.15%)
         occurrences all number
    12
    40
    6
    Face oedema
         subjects affected / exposed
    4 / 20 (20.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    4
    1
    1
    Chills
         subjects affected / exposed
    2 / 20 (10.00%)
    8 / 123 (6.50%)
    1 / 13 (7.69%)
         occurrences all number
    2
    11
    1
    Swelling face
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    6 / 20 (30.00%)
    28 / 123 (22.76%)
    6 / 13 (46.15%)
         occurrences all number
    9
    49
    6
    Oedema peripheral
         subjects affected / exposed
    6 / 20 (30.00%)
    19 / 123 (15.45%)
    3 / 13 (23.08%)
         occurrences all number
    6
    23
    8
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Drug hypersensitivity
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Nasal congestion
         subjects affected / exposed
    2 / 20 (10.00%)
    6 / 123 (4.88%)
    1 / 13 (7.69%)
         occurrences all number
    4
    6
    2
    Productive cough
         subjects affected / exposed
    1 / 20 (5.00%)
    5 / 123 (4.07%)
    2 / 13 (15.38%)
         occurrences all number
    1
    5
    3
    Pulmonary oedema
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    1
    2
    1
    Hypoxia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    2
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    1
    2
    1
    Wheezing
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    2
    2
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 20 (0.00%)
    11 / 123 (8.94%)
    0 / 13 (0.00%)
         occurrences all number
    0
    15
    0
    Cough
         subjects affected / exposed
    5 / 20 (25.00%)
    15 / 123 (12.20%)
    4 / 13 (30.77%)
         occurrences all number
    7
    17
    4
    Dyspnoea
         subjects affected / exposed
    3 / 20 (15.00%)
    17 / 123 (13.82%)
    1 / 13 (7.69%)
         occurrences all number
    4
    19
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 123 (2.44%)
    1 / 13 (7.69%)
         occurrences all number
    0
    3
    1
    Respiratory failure
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    4 / 20 (20.00%)
    10 / 123 (8.13%)
    0 / 13 (0.00%)
         occurrences all number
    4
    11
    0
    Confusional state
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 123 (0.81%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    Anxiety
         subjects affected / exposed
    1 / 20 (5.00%)
    5 / 123 (4.07%)
    2 / 13 (15.38%)
         occurrences all number
    1
    6
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 20 (20.00%)
    47 / 123 (38.21%)
    7 / 13 (53.85%)
         occurrences all number
    8
    98
    18
    Amylase increased
         subjects affected / exposed
    2 / 20 (10.00%)
    9 / 123 (7.32%)
    0 / 13 (0.00%)
         occurrences all number
    4
    18
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 20 (20.00%)
    12 / 123 (9.76%)
    1 / 13 (7.69%)
         occurrences all number
    7
    15
    1
    Lymphocyte count decreased
         subjects affected / exposed
    4 / 20 (20.00%)
    17 / 123 (13.82%)
    2 / 13 (15.38%)
         occurrences all number
    9
    43
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 20 (20.00%)
    45 / 123 (36.59%)
    5 / 13 (38.46%)
         occurrences all number
    5
    99
    7
    Blood bilirubin increased
         subjects affected / exposed
    1 / 20 (5.00%)
    10 / 123 (8.13%)
    1 / 13 (7.69%)
         occurrences all number
    1
    14
    2
    Blood culture positive
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Blood immunoglobulin G decreased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Blood lactate dehydrogenase
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 20 (10.00%)
    20 / 123 (16.26%)
    1 / 13 (7.69%)
         occurrences all number
    2
    23
    1
    Immunoglobulins decreased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Lipase increased
         subjects affected / exposed
    3 / 20 (15.00%)
    13 / 123 (10.57%)
    0 / 13 (0.00%)
         occurrences all number
    5
    15
    0
    Neutrophil count decreased
         subjects affected / exposed
    8 / 20 (40.00%)
    41 / 123 (33.33%)
    3 / 13 (23.08%)
         occurrences all number
    17
    101
    9
    Platelet count decreased
         subjects affected / exposed
    11 / 20 (55.00%)
    34 / 123 (27.64%)
    6 / 13 (46.15%)
         occurrences all number
    14
    67
    10
    Urine output decreased
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 123 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Weight decreased
         subjects affected / exposed
    3 / 20 (15.00%)
    8 / 123 (6.50%)
    3 / 13 (23.08%)
         occurrences all number
    3
    11
    5
    Weight increased
         subjects affected / exposed
    2 / 20 (10.00%)
    4 / 123 (3.25%)
    0 / 13 (0.00%)
         occurrences all number
    2
    5
    0
    Blood creatinine increased
         subjects affected / exposed
    3 / 20 (15.00%)
    16 / 123 (13.01%)
    0 / 13 (0.00%)
         occurrences all number
    3
    23
    0
    White blood cell count decreased
         subjects affected / exposed
    7 / 20 (35.00%)
    25 / 123 (20.33%)
    3 / 13 (23.08%)
         occurrences all number
    13
    41
    6
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    1 / 20 (5.00%)
    7 / 123 (5.69%)
    2 / 13 (15.38%)
         occurrences all number
    1
    9
    2
    Tachycardia
         subjects affected / exposed
    1 / 20 (5.00%)
    4 / 123 (3.25%)
    2 / 13 (15.38%)
         occurrences all number
    1
    4
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 20 (0.00%)
    8 / 123 (6.50%)
    3 / 13 (23.08%)
         occurrences all number
    0
    9
    3
    Presyncope
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Dizziness
         subjects affected / exposed
    3 / 20 (15.00%)
    9 / 123 (7.32%)
    2 / 13 (15.38%)
         occurrences all number
    3
    12
    2
    Sciatica
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Hypoaesthesia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    1
    3
    1
    Dysgeusia
         subjects affected / exposed
    2 / 20 (10.00%)
    10 / 123 (8.13%)
    1 / 13 (7.69%)
         occurrences all number
    2
    11
    2
    Paraesthesia
         subjects affected / exposed
    0 / 20 (0.00%)
    9 / 123 (7.32%)
    0 / 13 (0.00%)
         occurrences all number
    0
    9
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 20 (5.00%)
    8 / 123 (6.50%)
    0 / 13 (0.00%)
         occurrences all number
    1
    9
    0
    Blood and lymphatic system disorders
    Normocytic anaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Eosinophilia
         subjects affected / exposed
    0 / 20 (0.00%)
    7 / 123 (5.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    8
    0
    Anaemia
         subjects affected / exposed
    7 / 20 (35.00%)
    34 / 123 (27.64%)
    5 / 13 (38.46%)
         occurrences all number
    7
    56
    13
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    5
    Cataract
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Dry eye
         subjects affected / exposed
    0 / 20 (0.00%)
    5 / 123 (4.07%)
    1 / 13 (7.69%)
         occurrences all number
    0
    5
    1
    Eye irritation
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Vitreous floaters
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    6 / 20 (30.00%)
    16 / 123 (13.01%)
    2 / 13 (15.38%)
         occurrences all number
    7
    18
    2
    Oral pain
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 123 (2.44%)
    2 / 13 (15.38%)
         occurrences all number
    0
    3
    2
    Colitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Constipation
         subjects affected / exposed
    5 / 20 (25.00%)
    22 / 123 (17.89%)
    2 / 13 (15.38%)
         occurrences all number
    5
    24
    3
    Stomatitis
         subjects affected / exposed
    1 / 20 (5.00%)
    15 / 123 (12.20%)
    3 / 13 (23.08%)
         occurrences all number
    1
    21
    5
    Diarrhoea
         subjects affected / exposed
    9 / 20 (45.00%)
    41 / 123 (33.33%)
    9 / 13 (69.23%)
         occurrences all number
    13
    63
    18
    Haemorrhoids
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    2 / 13 (15.38%)
         occurrences all number
    0
    1
    2
    Nausea
         subjects affected / exposed
    9 / 20 (45.00%)
    31 / 123 (25.20%)
    6 / 13 (46.15%)
         occurrences all number
    12
    37
    6
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Gastritis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Dysphagia
         subjects affected / exposed
    1 / 20 (5.00%)
    5 / 123 (4.07%)
    1 / 13 (7.69%)
         occurrences all number
    1
    5
    1
    Dyspepsia
         subjects affected / exposed
    1 / 20 (5.00%)
    9 / 123 (7.32%)
    2 / 13 (15.38%)
         occurrences all number
    1
    9
    3
    Dry mouth
         subjects affected / exposed
    1 / 20 (5.00%)
    8 / 123 (6.50%)
    0 / 13 (0.00%)
         occurrences all number
    1
    8
    0
    Abdominal pain
         subjects affected / exposed
    2 / 20 (10.00%)
    13 / 123 (10.57%)
    4 / 13 (30.77%)
         occurrences all number
    2
    17
    4
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Rash erythematous
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 123 (2.44%)
    4 / 13 (30.77%)
         occurrences all number
    0
    3
    6
    Dermatitis acneiform
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Dry skin
         subjects affected / exposed
    2 / 20 (10.00%)
    13 / 123 (10.57%)
    3 / 13 (23.08%)
         occurrences all number
    2
    18
    6
    Eczema
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    3
    1
    Erythema
         subjects affected / exposed
    3 / 20 (15.00%)
    6 / 123 (4.88%)
    2 / 13 (15.38%)
         occurrences all number
    3
    12
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 123 (3.25%)
    1 / 13 (7.69%)
         occurrences all number
    0
    4
    1
    Night sweats
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 123 (3.25%)
    2 / 13 (15.38%)
         occurrences all number
    0
    4
    3
    Pain of skin
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    Rash pruritic
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    2 / 13 (15.38%)
         occurrences all number
    1
    3
    2
    Rash maculo-papular
         subjects affected / exposed
    7 / 20 (35.00%)
    21 / 123 (17.07%)
    2 / 13 (15.38%)
         occurrences all number
    7
    37
    7
    Rash macular
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    2
    Photosensitivity reaction
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Pruritus
         subjects affected / exposed
    3 / 20 (15.00%)
    20 / 123 (16.26%)
    3 / 13 (23.08%)
         occurrences all number
    4
    29
    4
    Rash
         subjects affected / exposed
    3 / 20 (15.00%)
    14 / 123 (11.38%)
    3 / 13 (23.08%)
         occurrences all number
    3
    31
    3
    Psoriasis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Acute kidney injury
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    3
    2
    1
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    2 / 20 (10.00%)
    4 / 123 (3.25%)
    0 / 13 (0.00%)
         occurrences all number
    3
    4
    0
    Pain in extremity
         subjects affected / exposed
    3 / 20 (15.00%)
    5 / 123 (4.07%)
    1 / 13 (7.69%)
         occurrences all number
    3
    5
    1
    Arthralgia
         subjects affected / exposed
    1 / 20 (5.00%)
    17 / 123 (13.82%)
    2 / 13 (15.38%)
         occurrences all number
    1
    24
    2
    Muscular weakness
         subjects affected / exposed
    1 / 20 (5.00%)
    3 / 123 (2.44%)
    2 / 13 (15.38%)
         occurrences all number
    2
    4
    2
    Bursitis
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Back pain
         subjects affected / exposed
    4 / 20 (20.00%)
    9 / 123 (7.32%)
    1 / 13 (7.69%)
         occurrences all number
    4
    9
    1
    Myalgia
         subjects affected / exposed
    1 / 20 (5.00%)
    7 / 123 (5.69%)
    1 / 13 (7.69%)
         occurrences all number
    1
    7
    1
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 20 (0.00%)
    7 / 123 (5.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    7
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 20 (5.00%)
    5 / 123 (4.07%)
    1 / 13 (7.69%)
         occurrences all number
    1
    5
    1
    Oral candidiasis
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    2 / 13 (15.38%)
         occurrences all number
    1
    2
    3
    Mucosal infection
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    1
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Pneumonia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 20 (5.00%)
    5 / 123 (4.07%)
    1 / 13 (7.69%)
         occurrences all number
    1
    5
    1
    Adenovirus infection
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Oesophageal candidiasis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 123 (0.81%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Influenza
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    2
    Eye infection
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    0
    2
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 20 (5.00%)
    4 / 123 (3.25%)
    4 / 13 (30.77%)
         occurrences all number
    1
    4
    5
    Decreased appetite
         subjects affected / exposed
    1 / 20 (5.00%)
    11 / 123 (8.94%)
    2 / 13 (15.38%)
         occurrences all number
    1
    12
    2
    Glucose tolerance impaired
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 123 (1.63%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    Hypophosphataemia
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 123 (0.81%)
    2 / 13 (15.38%)
         occurrences all number
    4
    1
    2
    Hyponatraemia
         subjects affected / exposed
    3 / 20 (15.00%)
    15 / 123 (12.20%)
    2 / 13 (15.38%)
         occurrences all number
    3
    20
    3
    Hypomagnesaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    6 / 123 (4.88%)
    1 / 13 (7.69%)
         occurrences all number
    1
    10
    1
    Hypokalaemia
         subjects affected / exposed
    6 / 20 (30.00%)
    13 / 123 (10.57%)
    4 / 13 (30.77%)
         occurrences all number
    7
    20
    4
    Hypocalcaemia
         subjects affected / exposed
    3 / 20 (15.00%)
    5 / 123 (4.07%)
    1 / 13 (7.69%)
         occurrences all number
    3
    5
    2
    Hyperglycaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    12 / 123 (9.76%)
    0 / 13 (0.00%)
         occurrences all number
    3
    18
    0
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 20 (10.00%)
    10 / 123 (8.13%)
    3 / 13 (23.08%)
         occurrences all number
    2
    12
    4
    Hypercalcaemia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 123 (1.63%)
    1 / 13 (7.69%)
         occurrences all number
    2
    2
    1
    Lactic acidosis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 123 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Hyperuricaemia
         subjects affected / exposed
    2 / 20 (10.00%)
    7 / 123 (5.69%)
    1 / 13 (7.69%)
         occurrences all number
    2
    7
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Mar 2019
    - Objective/endpoint alignment - Population clarification - Expansion Phase dose determination
    09 Aug 2019
    - Revised vital sign collection to occur at every visit, including C1D8, C1D15 and C2D15 visits - Added new sections with details related to participant data protection and quality assurance
    16 Sep 2019
    - Modified text to indicate the optimal dose for the Expansion Phase has been selected and that the optimal dose was selected based on the interim results of the Dose Optimization Phase - Added new section: “End of Study Definition" - Modified text to indicate that live vaccines are prohibited for 3 months after last dose of study drug

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    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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