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    Clinical Trial Results:
    A Randomized Multicenter, Open-label, Phase 2 Study Evaluating the Efficacy and Safety of Azacitidine Subcutaneous in Combination With Durvalumab (MEDI4736) in Previously Untreated Subjects with Higher-Risk Myelodysplastic Syndromes (MDS) or in Elderly (≥ 65 years) Acute Myeloid Leukemia (AML) Subjects Not Eligible for Hematopoietic Stem Cell Transplantation (HSCT).

    Summary
    EudraCT number
    		 2015-003596-30
    Trial protocol
    		 GB   NL   PT   ES   AT   DE   BE   PL   IT  
    Global end of trial date
    27 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    08 Jan 2023
    First version publication date
    08 Jan 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MEDI4736-MDS-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02775903
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Street Address: Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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
    25 Feb 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Evaluate the efficacy of subcutaneous (sc) azacitidine in combination with durvalumab as compared with subcutaneous azacitidine alone in the defined study population.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    03 Jun 2016
    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
    Austria: 11
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    Canada: 10
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    Germany: 21
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Poland: 18
    Country: Number of subjects enrolled
    Portugal: 3
    Country: Number of subjects enrolled
    Spain: 39
    Country: Number of subjects enrolled
    United Kingdom: 21
    Country: Number of subjects enrolled
    United States: 44
    Worldwide total number of subjects
    213
    EEA total number of subjects
    138
    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)
    12
    From 65 to 84 years
    173
    85 years and over
    28

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study consisted of 2 cohorts: • Adults with previously untreated intermediate, high or very high risk myelodysplastic syndromes (MDS) not eligible for hematopoietic stem cell transplantation (HSCT). • Adults with previously untreated acute myeloid leukemia (AML) ≥ 65 years and not eligible for HSCT with intermediate or poor cytogenetic risk.

    Pre-assignment
    Screening details
    		 Within each cohort participants were randomized in a 1:1 ratio to receive either azacitidine plus durvalumab or azacitidine alone. Randomization was stratified according to cytogenetic risk: • Very good, good and intermediate versus poor and very poor for MDS • Intermediate versus poor for AML .

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MDS: Azacitidine + Durvalumab
    Arm description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1500 mg on Day 1 Q4W

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    75 mg/m2 for 7 days every 4 weeks [Q4W])

    Arm title
    		 MDS: Azacitidine Alone
    Arm description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    75 mg/m2 for 7 days every 4 weeks [Q4W])

    Arm title
    		 AML: Azacitidine + Durvalumab
    Arm description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Durvalumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1500 mg on Day 1 Q4W

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    75 mg/m2 for 7 days every 4 weeks [Q4W])

    Arm title
    		 AML: Azacitidine Alone
    Arm description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    75 mg/m2 for 7 days every 4 weeks [Q4W])

    Number of subjects in period 1
    		MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Started
    42
    42
    64
    65
    Completed
    4
    1
    1
    5
    Not completed
    38
    41
    63
    60
         Adverse event, serious fatal
    7
    11
    12
    11
         Consent withdrawn by subject
    7
    5
    5
    8
         Adverse event, non-fatal
    -
    1
    12
    3
         Other reasons
    7
    8
    2
    12
         Progressive disease
    15
    14
    30
    20
         Lack of efficacy
    2
    2
    2
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MDS: Azacitidine + Durvalumab
    Reporting group description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    MDS: Azacitidine Alone
    Reporting group description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    AML: Azacitidine + Durvalumab
    Reporting group description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    AML: Azacitidine Alone
    Reporting group description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone Total
    Number of subjects
    		 42 42 64 65 213
    Age Categorical
    Units: participants
        < 65 years
    		 2 10 0 0 12
        ≥ 65 to < 75 years
    		 21 11 24 28 84
        ≥ 75 years
    		 19 21 40 37 117
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 72.5 ( 6.53 ) 73.2 ( 8.83 ) 76.2 ( 5.97 ) 75.3 ( 5.36 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 14 12 24 34 84
        Male
    		 28 30 40 31 129
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 5 2 6 3 16
        Not Hispanic or Latino
    		 30 33 39 41 143
        Unknown or Not Reported
    		 7 7 19 21 54
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0
        Asian
    		 2 1 0 0 3
        Black or African American
    		 1 0 0 1 2
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        White
    		 30 33 45 42 150
        Not Collected or Reported
    		 7 5 18 21 51
        Other
    		 2 3 1 1 7
    Eastern Cooperative Oncology Group (ECOG) Performance Status
    ECOG performance status is used to describe a patient’s level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: - 0 = Fully active, no restrictions; - 1 = Restricted activity but ambulatory, able to carry out work of a light nature; - 2 = Ambulatory and capable of all self-care but unable to carry out work activities; - 3 = Limited self-care, confined to bed or chair more than 50% of waking hours; - 4 = Completely disabled, no selfcare, confined to bed or chair; - 5 = Dead
    Units: Subjects
        0 - Fully active
    		 17 18 19 26 80
        1 - Restricted but ambulatory
    		 20 20 40 32 112
        2 - Ambulatory but unable to work
    		 3 4 5 7 19
        3 - Limited self-care
    		 0 0 0 0 0
        4 - Completely Disabled
    		 0 0 0 0 0
        Missing
    		 2 0 0 0 2

    End points

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    End points reporting groups
    Reporting group title
    MDS: Azacitidine + Durvalumab
    Reporting group description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    MDS: Azacitidine Alone
    Reporting group description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    AML: Azacitidine + Durvalumab
    Reporting group description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    AML: Azacitidine Alone
    Reporting group description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Primary: MDS Cohort: Overall Response Rate

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    End point title
    		 MDS Cohort: Overall Response Rate [1]
    End point description
    Overall response rate (ORR) is defined as the percentage of participants achieving a complete remission (CR), partial remission (PR), marrow complete remission (mCR), and/or hematological improvement (HI) based on International Working Group (IWG) 2006 response criteria for MDS and central review. CR: ≤ 5% myeloblasts in bone marrow (BM), and peripheral blood: hemoglobin ≥ 11 g/dL; platelets ≥ 100 × 10⁹/L; neutrophils ≥ 1.0 × 10⁹/L; blasts 0% PR: BM blasts decreased by ≥ 50% but still > 5%; peripheral blood as for CR mCR: BM ≤ 5% myeloblasts and decrease by ≥ 50% HI: Any of the following: •Hemoglobin increase by ≥ 1.5 g/dL or reduction of units of red blood cell (RBC) transfusions of at least 4 RBC transfusions/8 weeks compared with pretreatment •Absolute increase in platelets of ≥ 30 × 10⁹/L if pretreatment value > 20 × 10⁹/L or increase from < 20 × 10⁹/L to > 20 × 10⁹/L and by at least 100% •At least 100% increase in neutrophils and an absolute increase of > 0.5 × 10⁹/L
    End point type
    Primary
    End point timeframe
    Response was assessed following every 3 treatment cycles until treatment discontinuation; median duration of treatment was 239 days (AZA) and 215 days (DUR) in the AZA + DUR group and 210 days in the AZA alone group.
    Notes
    [1] - 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: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    42
    42
    Units: percentage of participants
        number (confidence interval 95%)
    61.9 (47.22 to 76.59)
    47.6 (32.51 to 62.72)
    Statistical analysis title
    		 Summary of Response
    Comparison groups
    MDS: Azacitidine Alone v MDS: Azacitidine + Durvalumab
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1838
    Method
    		 Wald asymptotic two-sided test
    Confidence interval

    Primary: AML Cohort: Overall Response Rate

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    End point title
    		 AML Cohort: Overall Response Rate [2]
    End point description
    Overall response rate for AML is defined as the percentage of participants achieving an overall response of morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) based on modified IWG 2003 response criteria for AML and central review. CR: The following conditions must be met: •Absolute neutrophil count (ANC) ≥ 1.0 x10⁹/L •Platelet count ≥ 100 x10⁹/L •The bone marrow should contain less than 5% blast cells; •Auer rods should not be detectable; •No platelet, or whole blood transfusions for 7days prior to the date of the hematology assessment. CRi: Defined as a morphologic complete remission but the ANC count may be < 1.0 x10⁹/L and/or the platelet count may be < 100 x10⁹/L.
    End point type
    Primary
    End point timeframe
    Response was assessed following every 3 treatment cycles until treatment discontinuation; median duration of treatment was 198 days (AZA) and 171 days (DUR) in the AZA + DUR group and 203 days in the AZA alone group.
    Notes
    [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: Endpoints are pre-specified for specific study arms
    End point values
    		 AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    64
    65
    Units: percentage of participants
        number (confidence interval 95%)
    31.3 (19.89 to 42.61)
    35.4 (23.76 to 47.01)
    Statistical analysis title
    		 Summary of Response
    Comparison groups
    AML: Azacitidine + Durvalumab v AML: Azacitidine Alone
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.618
    Method
    		 Wald asymptotic two-sided test
    Confidence interval

    Secondary: MDS Cohort: Kaplan Meier Estimate of Time to First Response

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    End point title
    		 MDS Cohort: Kaplan Meier Estimate of Time to First Response [3]
    End point description
    Time to first response is defined as the time from randomization to the earliest date any response (complete remission (CR), partial remission (PR), marrow complete remission (mCR), and/or hematological improvement (HI)) based on International Working Group (IWG) 2006 response criteria for MDS and central review. Participants who did not achieve any defined response were censored at the date of last adequate response assessment, disease progression, or death, whichever occurred first. Response was assessed following every 3 treatment cycles until treatment discontinuation.
    End point type
    Secondary
    End point timeframe
    From randomization to the earliest date any response (up to approximately 34 months)
    Notes
    [3] - 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: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    42
    42
    Units: Weeks
        median (confidence interval 95%)
    14.3 (11.3 to 20.9)
    18.4 (8.1 to 26.1)
    Statistical analysis title
    		 Summary of Time to First Response
    Comparison groups
    MDS: Azacitidine + Durvalumab v MDS: Azacitidine Alone
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    P-value
    		 = 0.7016
    Method
    		 Logrank
    Confidence interval
    Notes
    [4] - P-values were not part of the formal testing.

    Secondary: MDS Cohort: Kaplan Meier Estimate of Relapse-free Survival

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    End point title
    		 MDS Cohort: Kaplan Meier Estimate of Relapse-free Survival [5]
    End point description
    The time from the date of first documented response (complete remission (CR), partial remission (PR)) to the date of disease relapse or death from any cause, whichever occurred first according to the International Working Group (IWG) 2006 response criteria for MDS and central review. Participants who were still alive and progression-free were censored at the date of their last response assessment. Participants who received a subsequent therapy before the date of disease relapse or death were censored at the time of subsequent therapy. Relapse after CR or PR is defined as at least one of the following: •Return to pretreatment bone marrow blast % •Decrement of ≥ 50% from maximum remission/response levels in granulocytes or platelets •Reduction in hemoglobin concentration by ≥ 1.5 g/dL or transfusion dependence. Response was assessed following every 3 treatment cycles until treatment discontinuation. NOTE: 99999 = NA; insufficient number of participants with events
    End point type
    Secondary
    End point timeframe
    From randomization to to the date of disease relapse or death from any cause, whichever occurred first (up to approximately 34 months)
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    3
    4
    Units: Months
        median (confidence interval 95%)
    3.7 (3.0 to 99999)
    99999 (0.0 to 99999)
    Statistical analysis title
    		 Summary of Relapse-free Survival
    Comparison groups
    MDS: Azacitidine + Durvalumab v MDS: Azacitidine Alone
    Number of subjects included in analysis
    7
    Analysis specification
    Pre-specified
    Analysis type
    		 [6]
    P-value
    		 = 0.6076
    Method
    		 Logrank
    Confidence interval
    Notes
    [6] - P-values were not part of the formal testing.

    Secondary: MDS Cohort: Percentage of Participants who Achieved a Cytogenetic Response

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    End point title
    		 MDS Cohort: Percentage of Participants who Achieved a Cytogenetic Response [7]
    End point description
    Cytogenetic response is defined as the percentage of participants who achieved a complete cytogenetic response or partial cytogenetic response according to the International Working Group (IWG) 2006 response criteria and central review. Complete cytogenetic response: Disappearance of the baseline chromosomal abnormality without appearance of new abnormalities. Partial cytogenetic response: At least 50% reduction of the chromosomal abnormality. Response was assessed following every 3 treatment cycles until treatment discontinuation.
    End point type
    Secondary
    End point timeframe
    From randomization up to approximately 34 months
    Notes
    [7] - 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: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    21
    23
    Units: percentage of participants
        number (confidence interval 95%)
    47.6 (26.26 to 68.98)
    34.8 (15.32 to 54.25)
    Statistical analysis title
    		 Summary of Cytogenetic Response
    Comparison groups
    MDS: Azacitidine + Durvalumab v MDS: Azacitidine Alone
    Number of subjects included in analysis
    44
    Analysis specification
    Pre-specified
    Analysis type
    		 [8]
    P-value
    		 = 0.384
    Method
    		 Wald asymptotic two-sided test
    Confidence interval
    Notes
    [8] - P-values were not part of the formal testing.

    Secondary: MDS Cohort: Kaplan-Meier Estimate of Progression-free Survival (PFS)

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    End point title
    		 MDS Cohort: Kaplan-Meier Estimate of Progression-free Survival (PFS) [9]
    End point description
    Progression-free survival is defined as the time from randomization to the first documented progressive disease (PD), relapse, or death due to any cause during or after the treatment period, whichever occurred first, according to the International Working Group (IWG) 2006 response criteria for MDS and central review. Participants who were still alive and progression-free were censored at the date of their last response assessment. Progressive disease is defined as follows: - an increase in BM blasts relative to nadir: •If nadir less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts •If nadir 5% - 10% blasts: ≥ 50% increase in blasts to > 10% blasts •If nadir 10% - 20% blasts: ≥ 50% increase in blasts to > 20% blasts •If nadir 20% - 30% blasts: ≥ 50% increase in blasts to > 30% blasts And any of the following: •At least 50% decrement from maximum remission/response levels in granulocytes or platelets •Reduction in Hgb concentration by ≥ 2 g/dL •Transfusion dependence
    End point type
    Secondary
    End point timeframe
    From randomization to the first documented progressive disease (PD), relapse, or death due to any cause (up to approximately 34 months)
    Notes
    [9] - 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: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    42
    42
    Units: Months
        median (confidence interval 95%)
    8.7 (5.6 to 10.2)
    8.6 (3.4 to 11.2)
    Statistical analysis title
    		 Summary of Progression-free Survival
    Comparison groups
    MDS: Azacitidine + Durvalumab v MDS: Azacitidine Alone
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 [10]
    P-value
    		 = 0.8961
    Method
    		 Logrank
    Confidence interval
    Notes
    [10] - P-values were not part of the formal testing.

    Secondary: MDS Cohort: Kaplan-Meier Estimate of Duration of Response

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    End point title
    		 MDS Cohort: Kaplan-Meier Estimate of Duration of Response [11]
    End point description
    Duration of response is defined as the time from when the first overall response (complete remission (CR), partial remission (PR), marrow complete remission (mCR), and/or hematological improvement (HI)) was observed until relapse, progressive disease (PD), or death, as defined by the International Working Group (IWG) 2006 response criteria and central review. If no relapse, PD, or death was observed, the duration of response was censored at the last response assessment date that the participant was known to be progression-free. Response was assessed following every 3 treatment cycles until treatment discontinuation.
    End point type
    Secondary
    End point timeframe
    From randomization to the first overall response, or death (up to approximately 34 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: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    26
    20
    Units: Weeks
        median (confidence interval 95%)
    33.9 (22.1 to 47.4)
    39.7 (26.3 to 73.1)
    Statistical analysis title
    		 Summary of Duration of Response
    Comparison groups
    MDS: Azacitidine + Durvalumab v MDS: Azacitidine Alone
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 [12]
    P-value
    		 = 0.3591
    Method
    		 Logrank
    Confidence interval
    Notes
    [12] - P-values were not part of the formal testing.

    Secondary: MDS Cohort: Kaplan-Meier Estimate of Time to AML Transformation

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    End point title
    		 MDS Cohort: Kaplan-Meier Estimate of Time to AML Transformation [13]
    End point description
    Participants were monitored for transformation to acute myeloid leukemia (AML) until death, lost to follow-up, withdrawal of consent for further data collection, or the end of the trial. Time to transformation to AML is defined as the time from the date of randomization until the date the participant had documented transformation to AML (defined as at least 30% of myeloblasts in the bone marrow). Participants with no transformation to AML were censored at the date of their last disease assessment. NOTE: 99999 = NA; insufficient number of participants with events
    End point type
    Secondary
    End point timeframe
    From randomization to the date the participant had documented transformation to AML (up to approximately 34 months)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    42
    42
    Units: Months
        median (confidence interval 95%)
    20.8 (15.0 to 99999)
    27.7 (11.3 to 99999)
    Statistical analysis title
    		 Summary of AML Transformation
    Comparison groups
    MDS: Azacitidine + Durvalumab v MDS: Azacitidine Alone
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 [14]
    P-value
    		 = 0.9031
    Method
    		 Logrank
    Confidence interval
    Notes
    [14] - P-values were not part of the formal testing.

    Secondary: MDS Cohort: Percentage of Participants with Disease Transformation to AML

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    End point title
    		 MDS Cohort: Percentage of Participants with Disease Transformation to AML [15]
    End point description
    Disease transformation to acute myeloid leukemia (AML) is defined as at least 30% myeloblasts in the bone marrow. Participants were monitored for transformation to AML until death, lost to follow-up, withdrawal of consent for further data collection, or the end of the trial. Participants with no transformation to AML were censored at the date of their last disease assessment.
    End point type
    Secondary
    End point timeframe
    From randomization until death, lost to follow-up, withdrawal of consent for further data collection, or the end of the trial (up to approximately 34 months)
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone
    Number of subjects analysed
    42
    42
    Units: Percentage of participants
        number (not applicable)
    23.8
    19.0
    No statistical analyses for this end point

    Secondary: AML Cohort: Kaplan Meier Estimate of Time to First Response

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    End point title
    		 AML Cohort: Kaplan Meier Estimate of Time to First Response [16]
    End point description
    Time to first response is defined as the time between the date of randomization and the earliest date any response (CR or CRi) was observed based on the modified International Working Group (IWG) 2003 response criteria for AML and central review. Participants who did not achieve any defined response were censored at the date of last adequate response assessment, disease progression, or death, whichever occurred first. Response was assessed following every 3 treatment cycles until treatment discontinuation. NOTE: 99999 = NA; insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From randomization and the earliest date any response (up to approximately 34 months)
    Notes
    [16] - 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: Endpoints are pre-specified for specific study arms
    End point values
    		 AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    64
    65
    Units: Weeks
        median (confidence interval 95%)
    99999 (14.3 to 99999)
    25.3 (13.9 to 43.0)
    Statistical analysis title
    		 Summary of Time to Response
    Comparison groups
    AML: Azacitidine + Durvalumab v AML: Azacitidine Alone
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 [17]
    P-value
    		 = 0.2409
    Method
    		 Logrank
    Confidence interval
    Notes
    [17] - P-values were not part of the formal testing.

    Secondary: AML Cohort: Percentage of Participants who Achieved a Complete Cytogenetic Response

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    End point title
    		 AML Cohort: Percentage of Participants who Achieved a Complete Cytogenetic Response [18]
    End point description
    Complete cytogenetic response (CyCR) based on the modified International Working Group (IWG) 2003 response criteria is defined as morphologic complete remission with a reversion to a normal karyotype. The following conditions must be met: • Absolute neutrophil count (ANC) ≥ 1.0 x10⁹/L • Platelet count ≥ 100 x10⁹/L • The bone marrow should contain less than 5% blast cells; • Auer rods should not be detectable; • No platelet, or whole blood transfusions for 7days prior to the date of the hematology assessment. AND • Reversion to normal karyotype at time of CR (based on ≥ 10 metaphases). Response was assessed following every 3 treatment cycles until treatment discontinuation.
    End point type
    Secondary
    End point timeframe
    From randomization up to approximately 34 months)
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    53
    50
    Units: Percentage of participants
        number (confidence interval 95%)
    11.3 (2.79 to 19.85)
    16.0 (5.84 to 26.16)
    Statistical analysis title
    		 Summary of Complete Cytogenetic Response
    Comparison groups
    AML: Azacitidine + Durvalumab v AML: Azacitidine Alone
    Number of subjects included in analysis
    103
    Analysis specification
    Pre-specified
    Analysis type
    		 [19]
    P-value
    		 = 0.4894
    Method
    		 Wald asymptotic two-sided test
    Confidence interval
    Notes
    [19] - P-values were not part of the formal testing.

    Secondary: AML Cohort: Kaplan Meier Estimate of Relapse-free Survival

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    End point title
    		 AML Cohort: Kaplan Meier Estimate of Relapse-free Survival [20]
    End point description
    Relapse-free survival is defined as time from the date of first documented response (morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi)) to the date of disease relapse or death from any cause, whichever occurred first based on the modified International Working Group (IWG) 2003 response criteria for AML and central review. Participants who were still alive and progression-free were censored at the date of their last response assessment. Participants who received a subsequent therapy before the date of disease relapse or death were censored at the time of subsequent therapy.
    End point type
    Secondary
    End point timeframe
    From randomization to the date of disease relapse or death from any cause, whichever occurred first (up to approximately 34 months)
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    20
    23
    Units: Months
        median (confidence interval 95%)
    9.5 (5.0 to 15.0)
    12.2 (3.5 to 19.3)
    Statistical analysis title
    		 Summary of Relapse-Free Survival
    Comparison groups
    AML: Azacitidine + Durvalumab v AML: Azacitidine Alone
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 [21]
    P-value
    		 = 0.0688
    Method
    		 Logrank
    Confidence interval
    Notes
    [21] - P-values were not part of the formal testing.

    Secondary: AML Cohort: Percentage of Participants with Hematologic Improvement

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    End point title
    		 AML Cohort: Percentage of Participants with Hematologic Improvement [22]
    End point description
    Hematological improvement was defined as participants with a erythroid response (HI-E), platelet response (HI-P) or neutrophil response (HI-NE) for at least 8 weeks, according to the IWG 2006 response criteria: Hi-E (in participants with pretreatment hemoglobin < 11 g/dL or red blood cell (RBC)-transfusion dependent): Hemoglobin increase of ≥ 1.5 g/dL, or reduction in units of RBC transfusions of at least 4 RBC transfusions/8 weeks compared with the 8 weeks prior to pretreatment. HI-P (in participants with pretreatment platelet count < 100 × 10⁹/L): Absolute increase in platelets of ≥ 30 × 10⁹/L if pretreatment value > 20 × 10⁹/L or increase from < 20 × 10⁹/L to > 20 × 10⁹/L and by at least 100%. HI-N (in participants with pretreatment neutrophils < 1.0 × 10⁹/L): At least 100% increase in neutrophils and an absolute increase of > 0.5 × 10⁹/L. Response was assessed following every 3 treatment cycles until treatment discontinuation.
    End point type
    Secondary
    End point timeframe
    From randomization up to approximately 34 months
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    64
    65
    Units: Percentage of participants
        number (confidence interval 95%)
    42.2 (30.09 to 54.29)
    38.5 (26.63 to 50.29)
    No statistical analyses for this end point

    Secondary: AML Cohort: Kaplan-Meier Estimate of Duration of Response

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    End point title
    		 AML Cohort: Kaplan-Meier Estimate of Duration of Response [23]
    End point description
    Duration of response is defined as the time from the first response morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi)) was observed until relapse, PD, or death based on the IWG 2003 response criteria and central review. If no relapse, PD, or death was observed, the duration of response was censored at the last response assessment date that the participant was known to be progression-free. Response was assessed following every 3 treatment cycles until treatment discontinuation.
    End point type
    Secondary
    End point timeframe
    From randomization until relapse, PD, or death (up to approximately 34 months)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    20
    23
    Units: Weeks
        median (confidence interval 95%)
    24.6 (16.4 to 48.0)
    52.0 (15.1 to 84.0)
    Statistical analysis title
    		 Summary of Duration of Response
    Comparison groups
    AML: Azacitidine + Durvalumab v AML: Azacitidine Alone
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 [24]
    P-value
    		 = 0.0381
    Method
    		 Logrank
    Confidence interval
    Notes
    [24] - P-values were not part of the formal testing.

    Secondary: Number of Participants with Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants with Treatment-emergent Adverse Events (TEAEs)
    End point description
    TEAEs occurred or worsened on or after the first dose of study drug and within 90 days after last dose of durvalumab or 28 days after last dose of azacitidine. The intensity of AEs was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: Grade 1 (Mild): asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death due to AE. NOTE: 99999 = NA; Participants did not receive study drug associated with the category of TEAE.
    End point type
    Secondary
    End point timeframe
    From first dose to 90 days after last dose of durvalumab or 28 days after last dose of azacitidine proir to the extension study (up to approximately 34 months)
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    38
    41
    64
    62
    Units: Participants
        Any treatment-emergent adverse event (TEAE)
    38
    41
    64
    62
        TEAE related to DUR
    27
    99999
    50
    99999
        TEAE related to AZA
    31
    33
    56
    50
        TEAE related to DUR or AZA
    35
    33
    58
    50
        Grade 3 TEAE
    36
    30
    60
    50
        Grade 3 TEAE related to DUR
    18
    99999
    29
    99999
        Grade 3 TEAE related to AZA
    18
    16
    32
    27
        Grade 3 TEAE related to DUR or AZA
    22
    16
    38
    27
        Grade 4 TEAE
    33
    27
    43
    34
        Grade 4 TEAE related to DUR
    16
    99999
    18
    99999
        Grade 4 TEAE related to AZA
    19
    15
    27
    17
        Grade 4 TEAE related to DUR or AZA
    22
    15
    28
    17
        Grade 5 TEAE
    10
    9
    26
    11
        Grade 5 TEAE related to DUR
    2
    99999
    1
    99999
        Grade 5 TEAE related to AZA
    1
    1
    1
    1
        Grade 5 TEAE related to DUR or AZA
    2
    1
    1
    1
        Serious TEAE
    34
    29
    56
    45
        Serious TEAE related to DUR
    11
    99999
    33
    99999
        Serious TEAE related to AZA
    9
    10
    25
    16
        Serious TEAE related to DUR or AZA
    14
    10
    34
    16
        TEAE leading to discontinuation of DUR
    5
    99999
    21
    99999
        TEAE leading to discontinuation of AZA
    0
    1
    13
    3
        TEAE leading to discontinuation of DUR or AZA
    5
    1
    22
    3
        TEAE leading to dose reduction of AZA
    3
    6
    10
    2
        TEAE leading to dose interruption of DUR
    24
    99999
    34
    99999
        TEAE leading to dose interruption of AZA
    27
    19
    39
    32
        TEAE leading to dose interruption of DUR or AZA
    28
    19
    41
    32
        TEAE leading to ongoing DUR infusion interruption
    2
    99999
    2
    99999
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Overall Survival

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    End point title
    		 Kaplan-Meier Estimate of Overall Survival
    End point description
    Overall survival is defined as the time between randomization and death/censored date. Participants who were alive at the time of the clinical data cut-off were censored at the last known alive date. NOTE: 99999 = NA; insufficient number of participants with events.
    End point type
    Secondary
    End point timeframe
    From randomization to date of death or last known alive date (up to approximately 34 months)
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    42
    42
    64
    65
    Units: Months
        median (confidence interval 95%)
    11.6 (9.5 to 99999)
    16.3 (9.8 to 22.6)
    13.0 (10.3 to 17.3)
    14.4 (10.0 to 16.6)
    Statistical analysis title
    		 Summary of Overall Survival (AML)
    Comparison groups
    AML: Azacitidine + Durvalumab v AML: Azacitidine Alone
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    		 [25]
    P-value
    		 = 0.0691
    Method
    		 Logrank
    Confidence interval
    Notes
    [25] - P-values were not part of the formal testing.
    Statistical analysis title
    		 Summary of Overall Survival (MDS)
    Comparison groups
    MDS: Azacitidine + Durvalumab v MDS: Azacitidine Alone
    Number of subjects included in analysis
    84
    Analysis specification
    Pre-specified
    Analysis type
    		 [26]
    P-value
    		 = 0.8973
    Method
    		 Logrank
    Confidence interval
    Notes
    [26] - P-values were not part of the formal testing.

    Secondary: One-year Survival

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    End point title
    		 One-year Survival
    End point description
    One-year survival is defined as the probability of survival at 1 year from randomization and is represented by the Kaplan-Meier estimate of the percentage of participants alive after 1 year.
    End point type
    Secondary
    End point timeframe
    At 12 months after randomization
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    42
    42
    64
    65
    Units: Percentage of participants
    49
    58
    52
    55
    No statistical analyses for this end point

    Secondary: Durvalumab Serum Concentration

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    End point title
    		 Durvalumab Serum Concentration [27]
    End point description
    NOTE: The number of participants analyzed for each timepoint may vary depending on the number of participants with available serum concentration measurements.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 end of infusion (EOI), Cycle 2 Day 1 pre-infusion, Cycle 4 Day 1 pre-infusion and EOI, and Cycle 6 Day 1 pre-infusion
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoints are pre-specified for specific study arms
    End point values
    		 MDS: Azacitidine + Durvalumab AML: Azacitidine + Durvalumab
    Number of subjects analysed
    38
    62
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cycle 1 Day 1 end of infusion
    375548.511 ( 140777.0558 )
    378598.369 ( 201902.4363 )
        Cycle 2 Day 1 pre-infusion
    84380.032 ( 92174.3455 )
    54216.956 ( 28336.3692 )
        Cycle 4 Day 1 pre-infusion
    132266.794 ( 126971.6223 )
    78622.429 ( 41708.9956 )
        Cycle 4 Day 1 end of infusion
    433942.600 ( 233241.0329 )
    391523.395 ( 147928.1261 )
        Cycle 6 Day 1 pre-infusion
    114448.977 ( 64608.9007 )
    142517.871 ( 248212.8037 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Selected Hematology Parameters I

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    End point title
    		 Change from Baseline in Selected Hematology Parameters I
    End point description
    Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose. NOTE: The number of participants analyzed for each laboratory parameter may vary depending on the number of participants with available laboratory test measurements.
    End point type
    Secondary
    End point timeframe
    Cycle 2 - Days 1, 8, 15 and 22
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    37
    33
    56
    57
    Units: 10^9/L
    arithmetic mean (standard deviation)
        Hemoglobin (g/L)
    2.1 ( 15.66 )
    5.7 ( 18.94 )
    2.2 ( 13.67 )
    -3.0 ( 13.91 )
        Leukocytes (10^9/L)
    -1.330 ( 2.8158 )
    -0.497 ( 1.1452 )
    -2.050 ( 9.0236 )
    -0.941 ( 2.7708 )
        Lymphocytes (10^9/L)
    -0.242 ( 0.5314 )
    -0.085 ( 0.3904 )
    -0.394 ( 1.6995 )
    -0.262 ( 0.9024 )
        Neutrophils, Segmented (10^9/L)
    -0.665 ( 1.6364 )
    -0.266 ( 0.7576 )
    0.646 ( 0.7870 )
    -0.102 ( 0.7346 )
        Platelets (10^9/L)
    26.7 ( 112.92 )
    -2.6 ( 82.05 )
    25.9 ( 92.86 )
    -0.9 ( 167.88 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Selected Hematology Parameters II

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    End point title
    		 Change from Baseline in Selected Hematology Parameters II
    End point description
    Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.
    End point type
    Secondary
    End point timeframe
    Cycle 2 - Days 1, 8, 15 and 22
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    37
    33
    56
    57
    Units: g/L
        arithmetic mean (standard deviation)
    2.1 ( 15.66 )
    5.7 ( 18.94 )
    2.2 ( 13.67 )
    -3.0 ( 13.91 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Selected Chemistry Parameters I

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    End point title
    		 Change from Baseline in Selected Chemistry Parameters I
    End point description
    Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose.
    End point type
    Secondary
    End point timeframe
    Cycle 2 - Days 1, 8, 15 and 22
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    37
    33
    56
    57
    Units: g/L
        arithmetic mean (standard deviation)
    -1.8 ( 4.01 )
    -1.1 ( 2.93 )
    -1.8 ( 5.00 )
    -3.8 ( 4.78 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Selected Chemistry Parameters II

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    End point title
    		 Change from Baseline in Selected Chemistry Parameters II
    End point description
    Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose. NOTE: The number of participants analyzed for each laboratory parameter may vary depending on the number of participants with available laboratory test measurements.
    End point type
    Secondary
    End point timeframe
    Cycle 2 - Days 1, 8, 15 and 22
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    37
    33
    56
    57
    Units: U/L
    arithmetic mean (standard deviation)
        Alkaline Phosphatase (U/L)
    8.7 ( 15.71 )
    4.5 ( 13.90 )
    12.3 ( 55.70 )
    15.5 ( 68.53 )
        Alanine Aminotransferase (U/L)
    3.6 ( 16.96 )
    0.4 ( 9.40 )
    0.3 ( 21.05 )
    4.0 ( 19.41 )
        Aspartate Aminotransferase (U/L)
    0.9 ( 10.52 )
    -0.8 ( 5.73 )
    -0.9 ( 16.83 )
    0.5 ( 14.22 )
        Lipase (U/L)
    -5.4 ( 18.23 )
    -10.2 ( 25.80 )
    -2.0 ( 10.28 )
    3.1 ( 42.85 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Selected Chemistry Parameters III

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    End point title
    		 Change from Baseline in Selected Chemistry Parameters III
    End point description
    Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose. NOTE: The number of participants analyzed for each laboratory parameter may vary depending on the number of participants with available laboratory test measurements.
    End point type
    Secondary
    End point timeframe
    Cycle 2 - Days 1, 8, 15 and 22
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    37
    33
    56
    57
    Units: mmol/L
    arithmetic mean (standard deviation)
        Calcium (mmol/L)
    0.004 ( 0.1013 )
    0.016 ( 0.1008 )
    -0.003 ( 0.1523 )
    -0.039 ( 0.1189 )
        Glucose (mmol/L)
    -0.40 ( 2.210 )
    -0.19 ( 1.265 )
    -0.38 ( 2.513 )
    -0.02 ( 2.365 )
        Potassium (mmol/L)
    0.15 ( 0.416 )
    -0.01 ( 0.451 )
    0.02 ( 0.411 )
    0.04 ( 0.622 )
        Sodium (mmol/L)
    -0.2 ( 2.93 )
    0.3 ( 3.26 )
    -0.6 ( 4.49 )
    -1.6 ( 3.73 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Selected Chemistry Parameters IV

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    End point title
    		 Change from Baseline in Selected Chemistry Parameters IV
    End point description
    Baseline values are defined as the last assessment of a particular parameter prior to administration of the participants first dose. NOTE: The number of participants analyzed for each laboratory parameter may vary depending on the number of participants with available laboratory test measurements.
    End point type
    Secondary
    End point timeframe
    Cycle 2 - Days 1, 8, 15 and 22
    End point values
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Number of subjects analysed
    37
    33
    56
    57
    Units: umol/L
    arithmetic mean (standard deviation)
        Bilirubin (umol/L)
    2.2 ( 5.13 )
    1.2 ( 4.21 )
    2.4 ( 6.23 )
    -0.0 ( 5.31 )
        Creatinine (umol/L)
    -4.0 ( 14.77 )
    -2.9 ( 10.19 )
    2.3 ( 16.39 )
    -0.6 ( 15.93 )
        Urate (umol/L)
    6.8 ( 65.85 )
    -3.2 ( 67.06 )
    -15.1 ( 75.69 )
    -29.1 ( 80.85 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality was assessed from first dose to study completion. SAEs and NSAEs were assessed from first dose to 90 days after last dose of durvalumab or 28 days after last dose of azacitidine (up to approximately 66 months)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    MDS: Azacitidine + Durvalumab
    Reporting group description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    MDS: Azacitidine Alone
    Reporting group description
    		 Participants with MDS received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    AML: Azacitidine + Durvalumab
    Reporting group description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks (Q4W) in combination with 1500 mg intravenous durvalumab on Day 1 of every 4 week cycle for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Reporting group title
    AML: Azacitidine Alone
    Reporting group description
    		 Participants with AML received 75 mg/m² subcutaneous azacitidine for 7 days every 4 weeks for at least 6 cycles. Participants who benefited from treatment may have continued treatment until loss of that benefit, disease progression or other treatment discontinuation criterion were met.

    Serious adverse events
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    34 / 38 (89.47%)
    29 / 41 (70.73%)
    56 / 64 (87.50%)
    45 / 62 (72.58%)
         number of deaths (all causes)
    22
    27
    48
    42
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transformation to acute myeloid leukaemia
         subjects affected / exposed
    3 / 38 (7.89%)
    4 / 41 (9.76%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    4 / 64 (6.25%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    2 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Raynaud's phenomenon
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Cellulitis
    Additional description: Cellulitis of the right axillary region and respiratory distress
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    9 / 64 (14.06%)
    4 / 62 (6.45%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 9
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 9
    0 / 3
    Generalised oedema
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Granuloma
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injection site haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injection site reaction
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injection site vesicles
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 38 (13.16%)
    3 / 41 (7.32%)
    8 / 64 (12.50%)
    5 / 62 (8.06%)
         occurrences causally related to treatment / all
    1 / 5
    1 / 3
    3 / 9
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Reproductive system and breast disorders
    Female genital tract fistula
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostatitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    5 / 64 (7.81%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    5 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Platelet count decreased
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Synovial rupture
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transfusion reaction
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic fracture
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiogenic shock
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    Cerebral infarction
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cerebrovascular accident
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Intraventricular haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 38 (7.89%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cytopenia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    14 / 38 (36.84%)
    9 / 41 (21.95%)
    23 / 64 (35.94%)
    14 / 62 (22.58%)
         occurrences causally related to treatment / all
    5 / 21
    4 / 18
    12 / 41
    5 / 17
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    1 / 5
    2 / 2
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    2 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute abdomen
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune colitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 38 (7.89%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 1
    1 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    2 / 64 (3.13%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mouth haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Panniculitis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pemphigoid
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin lesion
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Toxic skin eruption
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    2 / 64 (3.13%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Calculus bladder
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle haemorrhage
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspergillus infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast abscess
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Corona virus infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterococcal infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gingivitis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injection site infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection fungal
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metapneumovirus infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Micrococcus infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 1
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Oesophageal infection
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Perineal cellulitis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    6 / 38 (15.79%)
    3 / 41 (7.32%)
    16 / 64 (25.00%)
    8 / 62 (12.90%)
         occurrences causally related to treatment / all
    2 / 9
    0 / 3
    11 / 25
    1 / 9
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    0 / 3
    0 / 1
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Progressive multifocal leukoencephalopathy
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 38 (2.63%)
    3 / 41 (7.32%)
    4 / 64 (6.25%)
    4 / 62 (6.45%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    0 / 2
    0 / 1
    Septic shock
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    1 / 1
    0 / 0
    Serratia sepsis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 38 (0.00%)
    2 / 41 (4.88%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal abscess
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Superinfection bacterial
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Fluid retention
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophagia
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 MDS: Azacitidine + Durvalumab MDS: Azacitidine Alone AML: Azacitidine + Durvalumab AML: Azacitidine Alone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    38 / 38 (100.00%)
    40 / 41 (97.56%)
    63 / 64 (98.44%)
    60 / 62 (96.77%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    4 / 64 (6.25%)
    4 / 62 (6.45%)
         occurrences all number
    5
    2
    8
    9
    Hypotension
         subjects affected / exposed
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    7 / 64 (10.94%)
    8 / 62 (12.90%)
         occurrences all number
    4
    2
    7
    8
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    9 / 38 (23.68%)
    14 / 41 (34.15%)
    19 / 64 (29.69%)
    12 / 62 (19.35%)
         occurrences all number
    12
    32
    30
    21
    General physical health deterioration
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences all number
    0
    3
    1
    1
    Fatigue
         subjects affected / exposed
    9 / 38 (23.68%)
    6 / 41 (14.63%)
    17 / 64 (26.56%)
    11 / 62 (17.74%)
         occurrences all number
    12
    6
    19
    12
    Influenza like illness
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    2
    1
    0
    1
    Injection site bruising
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Injection site erythema
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    6 / 64 (9.38%)
    5 / 62 (8.06%)
         occurrences all number
    2
    2
    8
    6
    Injection site pain
         subjects affected / exposed
    3 / 38 (7.89%)
    4 / 41 (9.76%)
    4 / 64 (6.25%)
    2 / 62 (3.23%)
         occurrences all number
    3
    4
    4
    2
    Injection site rash
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences all number
    3
    0
    1
    0
    Injection site reaction
         subjects affected / exposed
    3 / 38 (7.89%)
    4 / 41 (9.76%)
    10 / 64 (15.63%)
    7 / 62 (11.29%)
         occurrences all number
    4
    5
    13
    8
    Mucosal inflammation
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    4 / 64 (6.25%)
    2 / 62 (3.23%)
         occurrences all number
    0
    3
    5
    2
    Oedema
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    7 / 64 (10.94%)
    1 / 62 (1.61%)
         occurrences all number
    3
    1
    10
    1
    Oedema peripheral
         subjects affected / exposed
    14 / 38 (36.84%)
    7 / 41 (17.07%)
    18 / 64 (28.13%)
    9 / 62 (14.52%)
         occurrences all number
    16
    9
    29
    13
    Pain
         subjects affected / exposed
    3 / 38 (7.89%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    2 / 62 (3.23%)
         occurrences all number
    3
    1
    1
    2
    Pyrexia
         subjects affected / exposed
    12 / 38 (31.58%)
    13 / 41 (31.71%)
    23 / 64 (35.94%)
    21 / 62 (33.87%)
         occurrences all number
    18
    16
    43
    38
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    13 / 38 (34.21%)
    11 / 41 (26.83%)
    18 / 64 (28.13%)
    15 / 62 (24.19%)
         occurrences all number
    15
    12
    20
    20
    Dyspnoea
         subjects affected / exposed
    9 / 38 (23.68%)
    4 / 41 (9.76%)
    15 / 64 (23.44%)
    12 / 62 (19.35%)
         occurrences all number
    10
    4
    20
    14
    Dyspnoea exertional
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    0 / 62 (0.00%)
         occurrences all number
    3
    0
    3
    0
    Epistaxis
         subjects affected / exposed
    6 / 38 (15.79%)
    4 / 41 (9.76%)
    13 / 64 (20.31%)
    5 / 62 (8.06%)
         occurrences all number
    7
    5
    16
    7
    Oropharyngeal pain
         subjects affected / exposed
    2 / 38 (5.26%)
    4 / 41 (9.76%)
    4 / 64 (6.25%)
    3 / 62 (4.84%)
         occurrences all number
    5
    4
    5
    3
    Productive cough
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    1 / 64 (1.56%)
    0 / 62 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences all number
    0
    3
    2
    3
    Pharyngeal erythema
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    1 / 64 (1.56%)
    3 / 62 (4.84%)
         occurrences all number
    5
    2
    1
    3
    Confusional state
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    4 / 62 (6.45%)
         occurrences all number
    1
    0
    2
    4
    Insomnia
         subjects affected / exposed
    9 / 38 (23.68%)
    4 / 41 (9.76%)
    11 / 64 (17.19%)
    8 / 62 (12.90%)
         occurrences all number
    11
    7
    11
    9
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    3 / 62 (4.84%)
         occurrences all number
    2
    0
    0
    4
    Alanine aminotransferase increased
         subjects affected / exposed
    8 / 38 (21.05%)
    2 / 41 (4.88%)
    2 / 64 (3.13%)
    3 / 62 (4.84%)
         occurrences all number
    8
    3
    4
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    4 / 38 (10.53%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    2 / 62 (3.23%)
         occurrences all number
    5
    0
    3
    6
    Blood creatinine increased
         subjects affected / exposed
    6 / 38 (15.79%)
    2 / 41 (4.88%)
    6 / 64 (9.38%)
    3 / 62 (4.84%)
         occurrences all number
    8
    2
    8
    3
    Blood bilirubin increased
         subjects affected / exposed
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    4 / 64 (6.25%)
    2 / 62 (3.23%)
         occurrences all number
    8
    1
    4
    2
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    0 / 62 (0.00%)
         occurrences all number
    2
    3
    4
    0
    Weight decreased
         subjects affected / exposed
    2 / 38 (5.26%)
    5 / 41 (12.20%)
    9 / 64 (14.06%)
    5 / 62 (8.06%)
         occurrences all number
    2
    5
    10
    5
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    2 / 38 (5.26%)
    4 / 41 (9.76%)
    1 / 64 (1.56%)
    6 / 62 (9.68%)
         occurrences all number
    2
    4
    1
    7
    Fall
         subjects affected / exposed
    4 / 38 (10.53%)
    4 / 41 (9.76%)
    6 / 64 (9.38%)
    6 / 62 (9.68%)
         occurrences all number
    6
    5
    12
    6
    Skin laceration
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Infusion related reaction
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    3
    0
    0
    Transfusion reaction
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    4 / 62 (6.45%)
         occurrences all number
    3
    0
    2
    4
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    3 / 62 (4.84%)
         occurrences all number
    2
    0
    3
    3
    Tachycardia
         subjects affected / exposed
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    4 / 64 (6.25%)
    1 / 62 (1.61%)
         occurrences all number
    4
    2
    4
    1
    Atrial fibrillation
         subjects affected / exposed
    4 / 38 (10.53%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    2 / 62 (3.23%)
         occurrences all number
    6
    0
    3
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    8 / 38 (21.05%)
    3 / 41 (7.32%)
    6 / 64 (9.38%)
    7 / 62 (11.29%)
         occurrences all number
    10
    3
    8
    7
    Dizziness
         subjects affected / exposed
    6 / 38 (15.79%)
    8 / 41 (19.51%)
    6 / 64 (9.38%)
    4 / 62 (6.45%)
         occurrences all number
    8
    9
    7
    6
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 38 (0.00%)
    1 / 41 (2.44%)
    4 / 64 (6.25%)
    3 / 62 (4.84%)
         occurrences all number
    0
    1
    5
    3
    Syncope
         subjects affected / exposed
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences all number
    4
    2
    2
    0
    Sciatica
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    2 / 62 (3.23%)
         occurrences all number
    2
    1
    0
    2
    Blood and lymphatic system disorders
    Bone marrow failure
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    0
    4
    0
    0
    Anaemia
         subjects affected / exposed
    14 / 38 (36.84%)
    15 / 41 (36.59%)
    19 / 64 (29.69%)
    19 / 62 (30.65%)
         occurrences all number
    27
    23
    52
    42
    Febrile neutropenia
         subjects affected / exposed
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    5 / 64 (7.81%)
    9 / 62 (14.52%)
         occurrences all number
    4
    2
    9
    10
    Leukopenia
         subjects affected / exposed
    8 / 38 (21.05%)
    3 / 41 (7.32%)
    6 / 64 (9.38%)
    6 / 62 (9.68%)
         occurrences all number
    18
    3
    19
    9
    Neutropenia
         subjects affected / exposed
    23 / 38 (60.53%)
    21 / 41 (51.22%)
    20 / 64 (31.25%)
    21 / 62 (33.87%)
         occurrences all number
    68
    42
    63
    72
    Thrombocytopenia
         subjects affected / exposed
    19 / 38 (50.00%)
    18 / 41 (43.90%)
    24 / 64 (37.50%)
    27 / 62 (43.55%)
         occurrences all number
    39
    37
    43
    66
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 38 (0.00%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    4 / 62 (6.45%)
         occurrences all number
    0
    0
    0
    4
    Abdominal pain
         subjects affected / exposed
    3 / 38 (7.89%)
    1 / 41 (2.44%)
    7 / 64 (10.94%)
    6 / 62 (9.68%)
         occurrences all number
    4
    1
    8
    6
    Constipation
         subjects affected / exposed
    22 / 38 (57.89%)
    20 / 41 (48.78%)
    36 / 64 (56.25%)
    33 / 62 (53.23%)
         occurrences all number
    31
    30
    54
    56
    Diarrhoea
         subjects affected / exposed
    16 / 38 (42.11%)
    14 / 41 (34.15%)
    27 / 64 (42.19%)
    16 / 62 (25.81%)
         occurrences all number
    20
    21
    47
    22
    Dry mouth
         subjects affected / exposed
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences all number
    4
    1
    3
    1
    Dyspepsia
         subjects affected / exposed
    4 / 38 (10.53%)
    2 / 41 (4.88%)
    3 / 64 (4.69%)
    2 / 62 (3.23%)
         occurrences all number
    4
    3
    4
    2
    Gingival bleeding
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    6 / 64 (9.38%)
    2 / 62 (3.23%)
         occurrences all number
    2
    0
    14
    5
    Haemorrhoids
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    5 / 64 (7.81%)
    5 / 62 (8.06%)
         occurrences all number
    2
    2
    5
    5
    Mouth haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    4 / 62 (6.45%)
         occurrences all number
    1
    0
    2
    4
    Odynophagia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    2 / 62 (3.23%)
         occurrences all number
    2
    0
    0
    2
    Nausea
         subjects affected / exposed
    16 / 38 (42.11%)
    11 / 41 (26.83%)
    26 / 64 (40.63%)
    22 / 62 (35.48%)
         occurrences all number
    25
    17
    50
    37
    Stomatitis
         subjects affected / exposed
    2 / 38 (5.26%)
    3 / 41 (7.32%)
    6 / 64 (9.38%)
    4 / 62 (6.45%)
         occurrences all number
    3
    3
    8
    5
    Rectal haemorrhage
         subjects affected / exposed
    1 / 38 (2.63%)
    2 / 41 (4.88%)
    4 / 64 (6.25%)
    0 / 62 (0.00%)
         occurrences all number
    1
    2
    4
    0
    Vomiting
         subjects affected / exposed
    10 / 38 (26.32%)
    10 / 41 (24.39%)
    20 / 64 (31.25%)
    15 / 62 (24.19%)
         occurrences all number
    15
    15
    25
    23
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences all number
    3
    1
    3
    7
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    5 / 38 (13.16%)
    2 / 41 (4.88%)
    2 / 64 (3.13%)
    1 / 62 (1.61%)
         occurrences all number
    5
    2
    2
    3
    Ecchymosis
         subjects affected / exposed
    1 / 38 (2.63%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    4 / 62 (6.45%)
         occurrences all number
    1
    1
    1
    4
    Erythema
         subjects affected / exposed
    2 / 38 (5.26%)
    3 / 41 (7.32%)
    5 / 64 (7.81%)
    5 / 62 (8.06%)
         occurrences all number
    2
    4
    5
    5
    Night sweats
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Petechiae
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    2 / 62 (3.23%)
         occurrences all number
    3
    0
    4
    2
    Pruritus
         subjects affected / exposed
    5 / 38 (13.16%)
    5 / 41 (12.20%)
    8 / 64 (12.50%)
    6 / 62 (9.68%)
         occurrences all number
    8
    7
    11
    8
    Rash
         subjects affected / exposed
    7 / 38 (18.42%)
    3 / 41 (7.32%)
    10 / 64 (15.63%)
    4 / 62 (6.45%)
         occurrences all number
    8
    3
    11
    4
    Rash erythematous
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences all number
    3
    0
    2
    0
    Rash maculo-papular
         subjects affected / exposed
    3 / 38 (7.89%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    0 / 62 (0.00%)
         occurrences all number
    5
    0
    2
    0
    Skin lesion
         subjects affected / exposed
    3 / 38 (7.89%)
    2 / 41 (4.88%)
    3 / 64 (4.69%)
    2 / 62 (3.23%)
         occurrences all number
    4
    2
    4
    2
    Urticaria
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences all number
    2
    2
    1
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    4 / 38 (10.53%)
    0 / 41 (0.00%)
    5 / 64 (7.81%)
    1 / 62 (1.61%)
         occurrences all number
    4
    0
    6
    1
    Dysuria
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    3 / 62 (4.84%)
         occurrences all number
    2
    1
    0
    3
    Urinary incontinence
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences all number
    2
    1
    1
    2
    Urinary retention
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences all number
    2
    0
    5
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 38 (13.16%)
    3 / 41 (7.32%)
    11 / 64 (17.19%)
    7 / 62 (11.29%)
         occurrences all number
    5
    3
    12
    7
    Arthritis
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    2 / 64 (3.13%)
    2 / 62 (3.23%)
         occurrences all number
    2
    1
    3
    2
    Back pain
         subjects affected / exposed
    4 / 38 (10.53%)
    6 / 41 (14.63%)
    15 / 64 (23.44%)
    6 / 62 (9.68%)
         occurrences all number
    4
    6
    17
    6
    Muscle tightness
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Muscular weakness
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    1 / 62 (1.61%)
         occurrences all number
    2
    0
    3
    1
    Musculoskeletal pain
         subjects affected / exposed
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    8 / 64 (12.50%)
    3 / 62 (4.84%)
         occurrences all number
    4
    1
    10
    3
    Neck pain
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences all number
    2
    1
    1
    1
    Myalgia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences all number
    2
    1
    1
    1
    Pain in extremity
         subjects affected / exposed
    1 / 38 (2.63%)
    2 / 41 (4.88%)
    12 / 64 (18.75%)
    3 / 62 (4.84%)
         occurrences all number
    1
    2
    14
    3
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    3 / 38 (7.89%)
    5 / 41 (12.20%)
    7 / 64 (10.94%)
    5 / 62 (8.06%)
         occurrences all number
    3
    5
    10
    5
    Fungal infection
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    2
    1
    0
    1
    Gingivitis
         subjects affected / exposed
    0 / 38 (0.00%)
    3 / 41 (7.32%)
    1 / 64 (1.56%)
    2 / 62 (3.23%)
         occurrences all number
    0
    3
    1
    2
    Influenza
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    3 / 64 (4.69%)
    3 / 62 (4.84%)
         occurrences all number
    2
    1
    3
    3
    Laryngitis
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    2
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    4 / 38 (10.53%)
    5 / 41 (12.20%)
    3 / 64 (4.69%)
    7 / 62 (11.29%)
         occurrences all number
    4
    5
    4
    8
    Oral candidiasis
         subjects affected / exposed
    6 / 38 (15.79%)
    0 / 41 (0.00%)
    2 / 64 (3.13%)
    3 / 62 (4.84%)
         occurrences all number
    7
    0
    2
    3
    Oral herpes
         subjects affected / exposed
    2 / 38 (5.26%)
    2 / 41 (4.88%)
    4 / 64 (6.25%)
    2 / 62 (3.23%)
         occurrences all number
    2
    2
    4
    3
    Pharyngitis
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Paronychia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    4 / 64 (6.25%)
    7 / 62 (11.29%)
         occurrences all number
    2
    1
    4
    7
    Tooth infection
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    2 / 64 (3.13%)
    2 / 62 (3.23%)
         occurrences all number
    2
    1
    2
    2
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 38 (5.26%)
    4 / 41 (9.76%)
    3 / 64 (4.69%)
    4 / 62 (6.45%)
         occurrences all number
    2
    6
    3
    4
    Urinary tract infection
         subjects affected / exposed
    6 / 38 (15.79%)
    1 / 41 (2.44%)
    8 / 64 (12.50%)
    5 / 62 (8.06%)
         occurrences all number
    6
    1
    11
    5
    Vascular device infection
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    0 / 62 (0.00%)
         occurrences all number
    3
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    8 / 38 (21.05%)
    7 / 41 (17.07%)
    18 / 64 (28.13%)
    10 / 62 (16.13%)
         occurrences all number
    12
    13
    24
    10
    Gout
         subjects affected / exposed
    2 / 38 (5.26%)
    1 / 41 (2.44%)
    1 / 64 (1.56%)
    1 / 62 (1.61%)
         occurrences all number
    2
    1
    1
    1
    Hyperglycaemia
         subjects affected / exposed
    5 / 38 (13.16%)
    3 / 41 (7.32%)
    2 / 64 (3.13%)
    1 / 62 (1.61%)
         occurrences all number
    5
    3
    2
    3
    Hypoalbuminaemia
         subjects affected / exposed
    3 / 38 (7.89%)
    3 / 41 (7.32%)
    2 / 64 (3.13%)
    4 / 62 (6.45%)
         occurrences all number
    4
    4
    2
    5
    Hypocalcaemia
         subjects affected / exposed
    7 / 38 (18.42%)
    0 / 41 (0.00%)
    3 / 64 (4.69%)
    4 / 62 (6.45%)
         occurrences all number
    7
    0
    4
    7
    Hypokalaemia
         subjects affected / exposed
    5 / 38 (13.16%)
    2 / 41 (4.88%)
    13 / 64 (20.31%)
    12 / 62 (19.35%)
         occurrences all number
    7
    3
    16
    21
    Hypomagnesaemia
         subjects affected / exposed
    4 / 38 (10.53%)
    4 / 41 (9.76%)
    5 / 64 (7.81%)
    4 / 62 (6.45%)
         occurrences all number
    5
    7
    6
    5
    Hypophosphataemia
         subjects affected / exposed
    4 / 38 (10.53%)
    1 / 41 (2.44%)
    5 / 64 (7.81%)
    4 / 62 (6.45%)
         occurrences all number
    4
    1
    7
    7
    Hyponatraemia
         subjects affected / exposed
    7 / 38 (18.42%)
    3 / 41 (7.32%)
    2 / 64 (3.13%)
    3 / 62 (4.84%)
         occurrences all number
    9
    3
    2
    6
    Hypoproteinaemia
         subjects affected / exposed
    2 / 38 (5.26%)
    0 / 41 (0.00%)
    0 / 64 (0.00%)
    1 / 62 (1.61%)
         occurrences all number
    2
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Mar 2017
    Addition of an extra exclusion criteria, based on Investigator feedback. Table of events has been updated.
    05 Mar 2019
    Addition of Appendix O that provides an extension to the study to allow patients who were benefiting from treatment to continue treatment with either azacitidine alone or azacitidine and durvalumab

    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.
    Participants started the extension phase at the time of their next regularly scheduled dosing cycle for study drug azacitidine or azacitidine and durvalumab after Protocol Amendment 03.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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