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    Clinical Trial Results:
    A Phase 2, Open-Label, 2-Cohort, Multicenter Study of INCB050465, a PI3Kδ Inhibitor, in Relapsed or Refractory Mantle Cell Lymphoma Previously Treated With or Without a BTK Inhibitor

    Summary
    EudraCT number
    		 2017-003148-19
    Trial protocol
    		 DK   GB   CZ   BE   ES   IT  
    Global end of trial date
    30 Apr 2024

    Results information
    Results version number
    		 v1
    This version publication date
    16 Feb 2025
    First version publication date
    16 Feb 2025
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    INCB 50465-205 (CITADEL-205)
    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
    30 Apr 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Apr 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study was conducted to assess the efficacy of INCB050465 in terms of objective response rate (ORR) in participants with mantle cell lymphoma (MCL) that was relapsed or refractory after at least 1 but no more than 3 prior systemic treatment regimens.
    Protection of trial subjects
    This study was performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, GoodClinical Practices as defined in Title 21 of the United States Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as International Council on Harmonisation GoodClinical Practice consolidated guidelines (E6) and applicable regulatory requirements.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Czechia: 12
    Country: Number of subjects enrolled
    Germany: 3
    Country: Number of subjects enrolled
    Denmark: 9
    Country: Number of subjects enrolled
    Spain: 27
    Country: Number of subjects enrolled
    France: 28
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 21
    Country: Number of subjects enrolled
    Poland: 19
    Country: Number of subjects enrolled
    United States: 25
    Worldwide total number of subjects
    161
    EEA total number of subjects
    124
    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)
    39
    From 65 to 84 years
    115
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in the study at 76 investigative sites in France, Spain, the United States, Italy, Poland, Czech Republic, Great Britain, Denmark, Belgium, Germany, and Israel.

    Pre-assignment
    Screening details
    		 A total of 161 participants with relapsed or refractory mantle cell lymphoma who received 1-3 prior systemic therapies were enrolled. An additional participant was enrolled but not treated; he/she was not assigned to any treatment/cohort and was not included in the “Full Analysis Set” or “Safety Population” for analysis.

    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
    		 Cohort 1: Treatment A (Exposed to Ibrutinib)
    Arm description
    		 Participants received parsaclisib 20 milligrams (mg), orally, once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to 52 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.
    Arm type
    		 Experimental

    Investigational medicinal product name
    parsaclisib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg, 2.5 mg, 5 mg, and 20 mg tablets taken orally

    Arm title
    		 Cohort 1: Treatment B (Exposed to Ibrutinib)
    Arm description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to 116 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.
    Arm type
    		 Experimental

    Investigational medicinal product name
    parsaclisib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg, 2.5 mg, 5 mg, and 20 mg tablets taken orally

    Arm title
    		 Cohort 2: Treatment A (BTK Inhibitor Naïve)
    Arm description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 20 mg QW for up to approximately 145 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.
    Arm type
    		 Experimental

    Investigational medicinal product name
    parsaclisib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg, 2.5 mg, 5 mg, and 20 mg tablets taken orally

    Arm title
    		 Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Arm description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to approximately 136 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.
    Arm type
    		 Experimental

    Investigational medicinal product name
    parsaclisib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1 mg, 2.5 mg, 5 mg, and 20 mg tablets taken orally

    Number of subjects in period 1
    		Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Started
    12
    41
    31
    77
    Completed
    1
    5
    8
    29
    Not completed
    11
    36
    23
    48
         Adverse event, serious fatal
    11
    31
    19
    34
         Consent withdrawn by subject
    -
    3
    1
    5
         Participant Transitioned to Rollover Protocol
    -
    -
    2
    5
         Discomfort, Pain, and Radiographic Advancement
    -
    -
    -
    1
         Lost to follow-up
    -
    1
    1
    1
         Disease Progression
    -
    1
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Treatment A (Exposed to Ibrutinib)
    Reporting group description
    		 Participants received parsaclisib 20 milligrams (mg), orally, once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to 52 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.

    Reporting group title
    Cohort 1: Treatment B (Exposed to Ibrutinib)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to 116 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.

    Reporting group title
    Cohort 2: Treatment A (BTK Inhibitor Naïve)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 20 mg QW for up to approximately 145 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.

    Reporting group title
    Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to approximately 136 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.

    Reporting group values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve) Total
    Number of subjects
    		 12 41 31 77 161
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 4 12 6 17 39
        From 65-84 years
    		 8 28 22 57 115
        85 years and over
    		 0 1 3 3 7
    Age Continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 70.2 (53 to 82) 69.8 (48 to 89) 72.2 (43 to 89) 71.5 (51 to 90) -
    Sex: Female, Male
    Units: participants
        Female
    		 1 11 5 17 34
        Male
    		 11 30 26 60 127
    Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 3 2 4 5 14
        Not Hispanic or Latino
    		 6 28 21 57 112
        Not Reported
    		 1 5 6 8 20
        Unknown
    		 2 4 0 1 7
        Captured as "Other" in Database
    		 0 0 0 2 2
        Missing
    		 0 2 0 4 6
    Race, Customized
    Units: Subjects
        White
    		 11 37 24 64 136
        Black or African American
    		 0 0 0 2 2
        Asian
    		 0 0 0 1 1
        American-Indian/Alaska Native
    		 0 0 0 0 0
        Native Hawaiian/Pacific Islander
    		 0 0 0 0 0
        Captured as "Other" in Database
    		 1 1 5 3 10
        Missing
    		 0 3 2 7 12

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: Treatment A (Exposed to Ibrutinib)
    Reporting group description
    		 Participants received parsaclisib 20 milligrams (mg), orally, once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to 52 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.

    Reporting group title
    Cohort 1: Treatment B (Exposed to Ibrutinib)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to 116 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.

    Reporting group title
    Cohort 2: Treatment A (BTK Inhibitor Naïve)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 20 mg QW for up to approximately 145 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.

    Reporting group title
    Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to approximately 136 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.

    Primary: Objective Response Rate (ORR)

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    End point title
    		 Objective Response Rate (ORR) [1]
    End point description
    ORR=percentage of participants with complete response(CR) or partial response(PR) per revised response criteria for lymphomas,determined by independent review committee(IRC).Criteria for CR:1.Target nodes/nodal masses of lymph nodes,extralymphatic sites regressed to≤1.5cm in longest dimension transverse diameter of lesion(LDi);2.Absence of non-measured lesion;3.Organ enlargement regressed to normal;4.No new lesions;5.Normal bone marrow morphology;if indeterminate,immunohistochemistry negative.Criteria for PR:1.Lymph nodes,extralymphatic sites- ≥50%decrease in sum of product of perpendicular diameters for multiple lesions(SPD)of up to 6 target measurable nodes,extranodal sites;if lesion is too small to measure on computed tomography(CT),assign5mm×5mm as default;if no longer visible,0×0mm.Node>5mm×5mm but smaller than normal,use actual measurement.2.Absent/regressed non-measured lesions,no increase.3.Organ enlargement-Spleen regressed by>50%in length beyond normal.4.No new lesions.
    End point type
    Primary
    End point timeframe
    Up to 1016 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.
    End point values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Number of subjects analysed
    12 [2]
    41 [3]
    31 [4]
    77 [5]
    Units: percentage of participants
        number (confidence interval 95%)
    8.3 (0.2 to 38.5)
    39.0 (24.2 to 55.5)
    64.5 (45.4 to 80.8)
    71.4 (60.0 to 81.2)
    Notes
    [2] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [3] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [4] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [5] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR)

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    End point title
    		 Duration of Response (DOR)
    End point description
    DOR=time from first documented evidence of CR/PR until disease progression/death from any cause as determined by IRC. CR: 1.Target nodes/nodal masses of lymph nodes/extralymphatic sites regressed to ≤1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow normal by morphology; if indeterminate, immunohistochemistry negative. PR: 1.Lymph nodes/extralymphatic sites- a. ≥50% decrease in SPD of up to 6 target measurable nodes/extranodal sites; b. when a lesion is too small to measure on CT, assign 5 mm×5 mm as the default; c.when no longer visible, 0×0 mm. For a node >5 mm×5 mm but smaller than normal, use actual measurement. 2.Non-measured lesions- Absent/regressed, but no increase. 3. Organ enlargement-Spleen regressed by >50% in length beyond normal. 4.No new lesions. -999, 9999=The upper limit of the CI was not estimable due to the low number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to 1016 days
    End point values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Number of subjects analysed
    1 [6]
    16 [7]
    20 [8]
    55 [9]
    Units: months
        median (confidence interval 95%)
    9999 (-9999 to 9999)
    3.20 (1.87 to 7.95)
    17.45 (3.81 to 9999)
    13.01 (9.03 to 16.59)
    Notes
    [6] - Only participants with objective response were analyzed.
    [7] - Only participants with objective response were analyzed.
    [8] - Only participants with objective response were analyzed.
    [9] - Only participants with objective response were analyzed.
    No statistical analyses for this end point

    Secondary: Complete Response Rate (CRR)

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    End point title
    		 Complete Response Rate (CRR)
    End point description
    CRR is defined as the percentage of participants with a CR as defined by response criteria for lymphomas, as determined by an IRC. The criteria for CR included: 1.Target nodes/nodal masses of lymph nodes and extralymphatic sites must regress to ≤ 1.5 cm in LDi; 2. Absence of non-measured lesion; 3.Organ enlargement regressed to normal; 4.No new lesions; 5.Bone marrow must be normal by morphology; if indeterminate, immunohistochemistry negative.
    End point type
    Secondary
    End point timeframe
    Up to 1016 days
    End point values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Number of subjects analysed
    12 [10]
    41 [11]
    31 [12]
    77 [13]
    Units: percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 26.5)
    2.4 (0.1 to 12.9)
    22.6 (9.6 to 41.1)
    15.6 (8.3 to 25.6)
    Notes
    [10] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [11] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [12] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [13] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS)

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    End point title
    		 Progression-Free Survival (PFS)
    End point description
    PFS is defined as the time from the date of the first dose of study treatment until the earliest date of disease progression as determined by radiographic disease assessment provided by an IRC, or death from any cause. 9999=The upper limit of the 95% CI was not estimable due to the low number of participants with events.
    End point type
    Secondary
    End point timeframe
    Up to 1016 days
    End point values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Number of subjects analysed
    12 [14]
    41 [15]
    31 [16]
    77 [17]
    Units: months
        median (confidence interval 95%)
    3.94 (1.35 to 9999)
    3.68 (1.87 to 5.49)
    8.11 (5.29 to 21.62)
    13.83 (10.02 to 16.89)
    Notes
    [14] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [15] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [16] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [17] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    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 is defined as the time from the date of the first dose of study treatment until death from any cause. 9999=The upper limit of the confidence interval was not estimable because too few participants died.
    End point type
    Secondary
    End point timeframe
    Up to 1016 days
    End point values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Number of subjects analysed
    12 [18]
    41 [19]
    31 [20]
    77 [21]
    Units: months
        median (confidence interval 95%)
    10.91 (1.35 to 17.64)
    11.01 (7.23 to 17.12)
    33.48 (21.62 to 54.67)
    45.86 (34.20 to 9999)
    Notes
    [18] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [19] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [20] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    [21] - Full Analysis Set: all participants enrolled in the study who received ≥1 dose of parsaclisib
    No statistical analyses for this end point

    Secondary: Best Percent Change from Baseline in Target Lesion Size

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    End point title
    		 Best Percent Change from Baseline in Target Lesion Size
    End point description
    Target lesion size is measured by the sum of the product of diameters of all target lesion sizes and is determined by the IRC. The best percent change from Baseline is defined as the largest decrease, or smallest increase if no decrease available, from Baseline in target lesion sizes on/before new (next-line) anti-lymphoma therapy during the study. Baseline is the last nonmissing measurement obtained before the first administration of study drug. A negative percent change from Baseline indicates improvement.
    End point type
    Secondary
    End point timeframe
    Up to 1016 days
    End point values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Number of subjects analysed
    6 [22]
    32 [23]
    25 [24]
    68 [25]
    Units: percent change in lesion size
        arithmetic mean (standard deviation)
    -19.82 ( 35.926 )
    -9.51 ( 133.438 )
    -64.65 ( 53.360 )
    -67.54 ( 32.918 )
    Notes
    [22] - Full Analysis Set. Only participants with available data were analyzed.
    [23] - Full Analysis Set. Only participants with available data were analyzed.
    [24] - Full Analysis Set. Only participants with available data were analyzed.
    [25] - Full Analysis Set. Only participants with available data were analyzed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    End point description
    An adverse event (AE) is any untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug regardless of starting new anti-lymphoma therapy. A SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect or is considered to be an important medical event that may not result in death, be immediately life-threatening, or require hospitalization but may be considered serious when, based on appropriate medical judgment, the event may jeopardize the participant or require medical or surgical intervention.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to 2045 days
    End point values
    		 Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 2: Treatment A (BTK Inhibitor Naïve) Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Number of subjects analysed
    12 [26]
    41 [27]
    31 [28]
    77 [29]
    Units: percentage of participants
    number (not applicable)
        TEAEs
    83.3
    90.2
    93.5
    92.2
        SAEs
    41.7
    48.8
    38.7
    58.4
    Notes
    [26] - Safety Population: all enrolled participants who received ≥1 dose of parsaclisib
    [27] - Safety Population: all enrolled participants who received ≥1 dose of parsaclisib
    [28] - Safety Population: all enrolled participants who received ≥1 dose of parsaclisib
    [29] - Safety Population: all enrolled participants who received ≥1 dose of parsaclisib
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug up to 2045 days
    Adverse event reporting additional description
    Adverse events have been reported for members of the Safety Population, comprised of all enrolled participants who received at least 1 dose of parsaclisib.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    Cohort 1: Treatment B (Exposed to Ibrutinib)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to 116 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.

    Reporting group title
    Cohort 1: Treatment A (Exposed to Ibrutinib)
    Reporting group description
    		 Participants received parsaclisib 20 milligrams (mg), orally, once daily (QD) for 8 weeks followed by 20 mg once weekly (QW) for up to 52 weeks. Participants who were exposed to ibrutinib before enrollment were included in this group.

    Reporting group title
    Cohort 2: Treatment B (BTK Inhibitor Naïve)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 2.5 mg QD for up to approximately 136 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.

    Reporting group title
    Total
    Reporting group description
    		 Total

    Reporting group title
    Cohort 2: Treatment A (BTK Inhibitor Naïve)
    Reporting group description
    		 Participants received parsaclisib 20 mg, orally, QD for 8 weeks followed by 20 mg QW for up to approximately 145 weeks. Participants who were not exposed to BTK inhibitor before enrollment were included in this group.

    Serious adverse events
    		 Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 2: Treatment B (BTK Inhibitor Naïve) Total Cohort 2: Treatment A (BTK Inhibitor Naïve)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 41 (48.78%)
    5 / 12 (41.67%)
    45 / 77 (58.44%)
    82 / 161 (50.93%)
    12 / 31 (38.71%)
         number of deaths (all causes)
    31
    11
    34
    95
    19
         number of deaths resulting from adverse events
    3
    1
    8
    12
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myelomonocytic leukaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Basal cell carcinoma
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mantle cell lymphoma
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Oedema peripheral
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Nodule
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Peripheral swelling
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    4 / 161 (2.48%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    1 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Swelling
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Dyspnoea
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Eastern Cooperative Oncology Group performance status worsened
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Spinal fracture
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Arrhythmia supraventricular
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Transient ischaemic attack
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Leukocytosis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Autoimmune colitis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Ascites
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    6 / 77 (7.79%)
    8 / 161 (4.97%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    6 / 6
    8 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 12 (8.33%)
    11 / 77 (14.29%)
    15 / 161 (9.32%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    2 / 6
    1 / 1
    10 / 11
    13 / 18
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Intestinal perforation
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Incarcerated inguinal hernia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Oesophagitis ulcerative
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Nausea
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Vomiting
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Hepatobiliary disorders
    Hepatic cytolysis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Dermatitis psoriasiform
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Dermatitis exfoliative
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Eczema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    4 / 161 (2.48%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oligoarthritis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Spondylitis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Atypical pneumonia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    COVID-19
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Cytomegalovirus infection reactivation
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Cytomegalovirus colitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Endocarditis staphylococcal
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    Parainfluenzae virus infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Pneumonia
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    3 / 161 (1.86%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 1
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Respiratory tract infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    1 / 2
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Urinary tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetic metabolic decompensation
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    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
    Dehydration
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    4 / 161 (2.48%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 2
    3 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    1 / 31 (3.23%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Cohort 1: Treatment B (Exposed to Ibrutinib) Cohort 1: Treatment A (Exposed to Ibrutinib) Cohort 2: Treatment B (BTK Inhibitor Naïve) Total Cohort 2: Treatment A (BTK Inhibitor Naïve)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 41 (68.29%)
    9 / 12 (75.00%)
    66 / 77 (85.71%)
    130 / 161 (80.75%)
    27 / 31 (87.10%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 12 (8.33%)
    4 / 77 (5.19%)
    7 / 161 (4.35%)
    1 / 31 (3.23%)
         occurrences all number
    1
    1
    4
    7
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    7 / 41 (17.07%)
    0 / 12 (0.00%)
    11 / 77 (14.29%)
    21 / 161 (13.04%)
    3 / 31 (9.68%)
         occurrences all number
    7
    0
    14
    24
    3
    Fatigue
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 12 (16.67%)
    8 / 77 (10.39%)
    14 / 161 (8.70%)
    2 / 31 (6.45%)
         occurrences all number
    2
    2
    8
    14
    2
    Oedema peripheral
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 12 (16.67%)
    5 / 77 (6.49%)
    12 / 161 (7.45%)
    2 / 31 (6.45%)
         occurrences all number
    4
    3
    5
    14
    2
    Pyrexia
         subjects affected / exposed
    6 / 41 (14.63%)
    1 / 12 (8.33%)
    12 / 77 (15.58%)
    24 / 161 (14.91%)
    5 / 31 (16.13%)
         occurrences all number
    6
    1
    15
    27
    5
    Reproductive system and breast disorders
    Testicular oedema
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 12 (8.33%)
    4 / 77 (5.19%)
    11 / 161 (6.83%)
    3 / 31 (9.68%)
         occurrences all number
    3
    1
    4
    11
    3
    Cough
         subjects affected / exposed
    5 / 41 (12.20%)
    1 / 12 (8.33%)
    12 / 77 (15.58%)
    20 / 161 (12.42%)
    2 / 31 (6.45%)
         occurrences all number
    5
    1
    13
    21
    2
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    3 / 161 (1.86%)
    0 / 31 (0.00%)
         occurrences all number
    2
    1
    0
    3
    0
    Insomnia
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 12 (16.67%)
    3 / 77 (3.90%)
    5 / 161 (3.11%)
    0 / 31 (0.00%)
         occurrences all number
    0
    2
    3
    5
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    4 / 77 (5.19%)
    6 / 161 (3.73%)
    1 / 31 (3.23%)
         occurrences all number
    1
    0
    4
    6
    1
    Blood creatinine increased
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    5 / 77 (6.49%)
    9 / 161 (5.59%)
    2 / 31 (6.45%)
         occurrences all number
    3
    0
    7
    13
    3
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    5 / 77 (6.49%)
    6 / 161 (3.73%)
    0 / 31 (0.00%)
         occurrences all number
    1
    0
    6
    7
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    4 / 161 (2.48%)
    2 / 31 (6.45%)
         occurrences all number
    0
    0
    9
    11
    2
    Platelet count decreased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    2 / 77 (2.60%)
    5 / 161 (3.11%)
    2 / 31 (6.45%)
         occurrences all number
    0
    1
    2
    5
    2
    Respiratory rate increased
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Pseudomonas test positive
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    3 / 41 (7.32%)
    2 / 12 (16.67%)
    10 / 77 (12.99%)
    15 / 161 (9.32%)
    0 / 31 (0.00%)
         occurrences all number
    3
    2
    12
    17
    0
    Cardiac disorders
    Atrial flutter
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 12 (8.33%)
    1 / 77 (1.30%)
    4 / 161 (2.48%)
    0 / 31 (0.00%)
         occurrences all number
    2
    1
    1
    4
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 12 (16.67%)
    1 / 77 (1.30%)
    8 / 161 (4.97%)
    3 / 31 (9.68%)
         occurrences all number
    2
    2
    1
    9
    4
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    8 / 41 (19.51%)
    3 / 12 (25.00%)
    6 / 77 (7.79%)
    21 / 161 (13.04%)
    4 / 31 (12.90%)
         occurrences all number
    10
    4
    9
    27
    4
    Eosinophilia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    3 / 77 (3.90%)
    5 / 161 (3.11%)
    2 / 31 (6.45%)
         occurrences all number
    0
    0
    3
    5
    2
    Neutropenia
         subjects affected / exposed
    6 / 41 (14.63%)
    2 / 12 (16.67%)
    10 / 77 (12.99%)
    21 / 161 (13.04%)
    3 / 31 (9.68%)
         occurrences all number
    9
    2
    12
    27
    4
    Thrombocytopenia
         subjects affected / exposed
    3 / 41 (7.32%)
    1 / 12 (8.33%)
    5 / 77 (6.49%)
    11 / 161 (6.83%)
    2 / 31 (6.45%)
         occurrences all number
    5
    1
    6
    14
    2
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Vertigo
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 12 (8.33%)
    1 / 77 (1.30%)
    3 / 161 (1.86%)
    0 / 31 (0.00%)
         occurrences all number
    1
    1
    1
    3
    0
    Abdominal pain
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 12 (0.00%)
    4 / 77 (5.19%)
    8 / 161 (4.97%)
    1 / 31 (3.23%)
         occurrences all number
    3
    0
    4
    8
    1
    Eructation
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Dysphagia
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    1 / 77 (1.30%)
    5 / 161 (3.11%)
    2 / 31 (6.45%)
         occurrences all number
    2
    0
    1
    5
    2
    Dyspepsia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    3 / 77 (3.90%)
    5 / 161 (3.11%)
    2 / 31 (6.45%)
         occurrences all number
    0
    0
    3
    5
    2
    Diarrhoea
         subjects affected / exposed
    9 / 41 (21.95%)
    2 / 12 (16.67%)
    26 / 77 (33.77%)
    45 / 161 (27.95%)
    8 / 31 (25.81%)
         occurrences all number
    18
    3
    40
    72
    11
    Constipation
         subjects affected / exposed
    4 / 41 (9.76%)
    0 / 12 (0.00%)
    12 / 77 (15.58%)
    19 / 161 (11.80%)
    3 / 31 (9.68%)
         occurrences all number
    5
    0
    13
    21
    3
    Colitis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    3 / 77 (3.90%)
    4 / 161 (2.48%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    3
    4
    0
    Nausea
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 12 (16.67%)
    8 / 77 (10.39%)
    16 / 161 (9.94%)
    4 / 31 (12.90%)
         occurrences all number
    3
    2
    8
    17
    4
    Stomatitis
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 12 (8.33%)
    2 / 77 (2.60%)
    5 / 161 (3.11%)
    1 / 31 (3.23%)
         occurrences all number
    1
    1
    2
    5
    1
    Vomiting
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 12 (8.33%)
    4 / 77 (5.19%)
    9 / 161 (5.59%)
    2 / 31 (6.45%)
         occurrences all number
    2
    1
    4
    9
    2
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    5 / 77 (6.49%)
    6 / 161 (3.73%)
    0 / 31 (0.00%)
         occurrences all number
    1
    0
    5
    6
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    1 / 31 (3.23%)
         occurrences all number
    0
    1
    0
    2
    1
    Pruritus
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 12 (8.33%)
    6 / 77 (7.79%)
    9 / 161 (5.59%)
    1 / 31 (3.23%)
         occurrences all number
    2
    1
    6
    10
    1
    Rash
         subjects affected / exposed
    4 / 41 (9.76%)
    1 / 12 (8.33%)
    16 / 77 (20.78%)
    23 / 161 (14.29%)
    2 / 31 (6.45%)
         occurrences all number
    4
    1
    19
    26
    2
    Rash maculo-papular
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    3 / 77 (3.90%)
    7 / 161 (4.35%)
    2 / 31 (6.45%)
         occurrences all number
    2
    0
    3
    7
    2
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 12 (16.67%)
    3 / 77 (3.90%)
    6 / 161 (3.73%)
    0 / 31 (0.00%)
         occurrences all number
    2
    2
    5
    9
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 41 (9.76%)
    0 / 12 (0.00%)
    5 / 77 (6.49%)
    11 / 161 (6.83%)
    2 / 31 (6.45%)
         occurrences all number
    4
    0
    6
    12
    2
    Back pain
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    6 / 77 (7.79%)
    12 / 161 (7.45%)
    4 / 31 (12.90%)
         occurrences all number
    2
    0
    6
    12
    4
    Pain in extremity
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    6 / 161 (3.73%)
    2 / 31 (6.45%)
         occurrences all number
    2
    0
    3
    7
    2
    Myalgia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    4 / 77 (5.19%)
    5 / 161 (3.11%)
    1 / 31 (3.23%)
         occurrences all number
    0
    0
    4
    6
    2
    Muscle spasms
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    6 / 161 (3.73%)
    2 / 31 (6.45%)
         occurrences all number
    2
    0
    2
    6
    2
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    5 / 161 (3.11%)
    2 / 31 (6.45%)
         occurrences all number
    1
    0
    2
    5
    2
    COVID-19
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 12 (0.00%)
    4 / 77 (5.19%)
    6 / 161 (3.73%)
    2 / 31 (6.45%)
         occurrences all number
    0
    0
    4
    6
    2
    Nasopharyngitis
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 12 (16.67%)
    3 / 77 (3.90%)
    8 / 161 (4.97%)
    2 / 31 (6.45%)
         occurrences all number
    2
    3
    4
    11
    2
    Rhinitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    0 / 77 (0.00%)
    3 / 161 (1.86%)
    2 / 31 (6.45%)
         occurrences all number
    1
    0
    0
    3
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 12 (8.33%)
    2 / 77 (2.60%)
    7 / 161 (4.35%)
    3 / 31 (9.68%)
         occurrences all number
    2
    1
    3
    10
    4
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    3 / 77 (3.90%)
    6 / 161 (3.73%)
    2 / 31 (6.45%)
         occurrences all number
    1
    0
    3
    6
    2
    Viral infection
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    1 / 77 (1.30%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    4 / 41 (9.76%)
    2 / 12 (16.67%)
    7 / 77 (9.09%)
    14 / 161 (8.70%)
    1 / 31 (3.23%)
         occurrences all number
    4
    2
    7
    14
    1
    Hypernatraemia
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    2 / 161 (1.24%)
    0 / 31 (0.00%)
         occurrences all number
    1
    1
    0
    2
    0
    Hyperuricaemia
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 12 (8.33%)
    3 / 77 (3.90%)
    8 / 161 (4.97%)
    2 / 31 (6.45%)
         occurrences all number
    4
    1
    6
    13
    2
    Malnutrition
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 12 (8.33%)
    0 / 77 (0.00%)
    1 / 161 (0.62%)
    0 / 31 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    2 / 77 (2.60%)
    5 / 161 (3.11%)
    2 / 31 (6.45%)
         occurrences all number
    1
    0
    2
    5
    2
    Hypokalaemia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 12 (0.00%)
    12 / 77 (15.58%)
    13 / 161 (8.07%)
    0 / 31 (0.00%)
         occurrences all number
    1
    0
    16
    17
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Nov 2017
    The primary purpose of this amendment was to address changes requested by the European Regulatory Agency.
    31 Jan 2018
    The primary purpose of this amendment was to institute hematology testing every 2 weeks for the first 8 weeks of dosing.
    16 Jul 2018
    The primary purpose of this amendment was to modify the dose reduction schedules.
    07 Dec 2018
    The primary purpose of the amendment was to increase the number of participants in each cohort to better understand the safety and efficacy of INCB050465 administered at one of the two treatment regimens.
    29 Aug 2019
    The primary purpose of this amendment was to add 10 more participants to Cohort 2.
    23 Dec 2019
    The primary purpose of this amendment was to provide additional guidance on dose modification in the event of diarrhea and colitis and to define the end of the study, including the option to receive continued treatment with INCB050465 in a rollover protocol.
    30 Jan 2020
    The primary purpose of this amendment was to close enrollment for Cohort 1 before reaching the target enrollment (n = 90).
    07 Sep 2022
    The primary purpose of this amendment was to describe risks associated with COVID-19.

    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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