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    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled phase II multi-center study of intravenous MBG453 added to hypomethylating agents in adult subjects with intermediate, high or very high-risk myelodysplastic syndrome (MDS) as per IPSS-R criteria Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.

    Summary
    EudraCT number
    		 2018-004479-11
    Trial protocol
    		 ES   FR   GB   DE   CZ   AT   GR   HU   NO   BE   IT  
    Global end of trial date
    15 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jul 2025
    First version publication date
    30 Jul 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CMBG453B12201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03946670
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma, AG
    Sponsor organisation address
    Lichtstrasse 35, Basel, Switzerland, 4056
    Public contact
    Clinical Disclosure Office, Novartis Pharm, AG, 41 8613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharm, AG, 41 8613241111, novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Apr 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine if sabatolimab combined with standard HMA therapy improves PFS in subjects with intermediate, high or very high risk MDS. To determine if sabatolimab combined with standard HMA therapy improves complete remission in subjects with intermediate, high, or very high risk MDS
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Jun 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Belgium: 5
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    United Kingdom: 1
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Hong Kong: 5
    Country: Number of subjects enrolled
    Hungary: 4
    Country: Number of subjects enrolled
    Italy: 17
    Country: Number of subjects enrolled
    Japan: 22
    Country: Number of subjects enrolled
    Korea, Democratic People's Republic of: 3
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Taiwan: 11
    Country: Number of subjects enrolled
    Türkiye: 8
    Country: Number of subjects enrolled
    United States: 16
    Worldwide total number of subjects
    127
    EEA total number of subjects
    58
    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)
    16
    From 65 to 84 years
    108
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 47 centers across 17 countries enrolled subjects in this study.

    Pre-assignment
    Screening details
    		 Informed consent was obtained from each subject in writing at screening before any study specific procedure was performed.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 MBG453 + hypomethylating agents (HMA)
    Arm description
    		 Patients were taking MBG453 plus hypomethylating agents
    Arm type
    		 Experimental

    Investigational medicinal product name
    Hypomethylating agent (HMA): decitabine or azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection, Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Decitabine (IV) 20 mg/m^2 from Day 1 to Day 5, azacitidine (SC or IV) 75 mg/m^2 from Day 1 to Day 7 or Day 1 to Day 5 plus Day 8 to Day 9, per Investigator's choice based on system organ class (SOC)

    Investigational medicinal product name
    Sabatolimab (MBG453)
    Investigational medicinal product code
    MBG453
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use, Implantation
    Dosage and administration details
    Sabatolimab solution for injection was supplied to the Investigators at dose strength of 100 mg/1mL and 400 mg/ 4 mL

    Arm title
    		 Placebo + hypomethylating agents (HMA)
    Arm description
    		 Patients were taking placebo plus hypomethylating agents
    Arm type
    		 Placebo

    Investigational medicinal product name
    Hypomethylating agent (HMA): decitabine or azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for injection, Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    Decitabine (IV) 20 mg/m^2 from Day 1 to Day 5, azacitidine (SC or IV) 75 mg/m^2 from Day 1 to Day 7 or Day 1 to Day 5 plus Day 8 to Day 9, per Investigator's choice based on system organ class (SOC)

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravenous use, Implantation
    Dosage and administration details
    Placebo solution for injection was supplied to the Investigators at dose strength of 100 mg/1mL and 400 mg/ 4 mL

    Number of subjects in period 1
    		MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Started
    65
    62
    Treated
    64
    61
    Not treated
    1
    1
    Discontinued from treatment
    64
    61
    Completed
    0
    0
    Not completed
    65
    62
         Adverse event, serious fatal
    5
    8
         Physician decision
    6
    5
         Subject Decision
    4
    5
         Adverse event, non-fatal
    7
    10
         Study Terminated By Sponsor
    2
    -
         Not Treated
    1
    1
         Progressive Disease
    34
    27
         New Therapy For Study Indication
    1
    -
         HSCT Planned
    5
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    MBG453 + hypomethylating agents (HMA)
    Reporting group description
    		 Patients were taking MBG453 plus hypomethylating agents

    Reporting group title
    Placebo + hypomethylating agents (HMA)
    Reporting group description
    		 Patients were taking placebo plus hypomethylating agents

    Reporting group values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA) Total
    Number of subjects
    		 65 62 127
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 6 10 16
        From 65-84 years
    		 57 51 108
        85 years and over
    		 2 1 3
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 71.9 ( 6.70 ) 71.3 ( 9.64 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 24 17 41
        Male
    		 41 45 86
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 44 33 77
        Asian
    		 17 25 42
        Black or African American
    		 0 1 1
        Unknown
    		 4 3 7

    End points

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    End points reporting groups
    Reporting group title
    MBG453 + hypomethylating agents (HMA)
    Reporting group description
    		 Patients were taking MBG453 plus hypomethylating agents

    Reporting group title
    Placebo + hypomethylating agents (HMA)
    Reporting group description
    		 Patients were taking placebo plus hypomethylating agents

    Primary: Complete Remission (CR) Rate

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    End point title
    		 Complete Remission (CR) Rate
    End point description
    CR: where the Bone marrow: ≤ 5% blasts with normal maturation of all cell lineages and Peripheral blood: where Hgb ≥ 10 g/dL AND Platelets ≥ 100*109/L AND Neutrophils ≥ 1.0*109/L AND Peripheral blasts 0%. Modified response criteria According to International Working Group (IWG) and as per World Health Organization (WHO) criteria for Myelodysplastic syndromes (MDS) as per investigator assessment.
    End point type
    Primary
    End point timeframe
    average of 7 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Percentage of participants
        number (confidence interval 95%)
    21.5 (12.3 to 33.5)
    17.7 (9.2 to 29.5)
    Statistical analysis title
    		 CR rate Analysis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.769
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Primary: Progression Free Survival (PFS)

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    End point title
    		 Progression Free Survival (PFS)
    End point description
    Defined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment.
    End point type
    Primary
    End point timeframe
    approx. 32 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: months
        median (confidence interval 95%)
    11.07 (7.62 to 17.61)
    8.48 (6.93 to 11.30)
    Statistical analysis title
    		 PFS Analysis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1022
    Method
    		 Logrank
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.749
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.479
         upper limit
    		 1.173

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Time from randomization to death due to any cause
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Months
        median (confidence interval 95%)
    19.12 (13.90 to 30.03)
    18.00 (13.11 to 25.43)
    Statistical analysis title
    		 OS Analysis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.808
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.542
         upper limit
    		 1.205

    Secondary: Progression Free Survival (PFS) - Final PFS

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    End point title
    		 Progression Free Survival (PFS) - Final PFS
    End point description
    Defined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause. This is an update of the Primary Outcome Measure PFS with data collected after assessment of the primary results.
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: months
        median (confidence interval 95%)
    11.07 (7.62 to 16.59)
    8.48 (6.93 to 11.30)
    Statistical analysis title
    		 Final PFS Analysis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.795
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.521
         upper limit
    		 1.212

    Secondary: Leukemia-free Survival (LFS)

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    End point title
    		 Leukemia-free Survival (LFS)
    End point description
    LFS is defined as the time from randomization to ≥ 20% blasts in bone marrow/peripheral blood (per World Health Organization (WHO) 2016 classification) or diagnosis of extramedullary acute leukemia or death due to any cause.
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Months
        median (confidence interval 95%)
    16.82 (8.80 to 28.58)
    13.63 (9.82 to 21.16)
    Statistical analysis title
    		 LFS Analysis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.906
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 1.44

    Secondary: Event-free Survival (EFS)

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    End point title
    		 Event-free Survival (EFS)
    End point description
    EFS is defined as the time from randomization to lack of reaching complete response (CR) within the first 6 months, relapse from CR or death due to any cause, whichever occurs first. CR and relapse from CR were defined according to International Working Group (IWG) for Myelodysplastic Syndromes (MDS) as per Investigator assessment. For participants not reaching CR within the first 6 months, an EFS event at day 1 was considered.
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Months
        median (confidence interval 95%)
    0.03 (0 to 999)
    0.03 (0 to 999)
    Statistical analysis title
    		 EFS Analysis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.589
         upper limit
    		 1.343

    Secondary: Duration of Complete Remission

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    End point title
    		 Duration of Complete Remission
    End point description
    Duration of complete response is the time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    15
    13
    Units: Months
        median (confidence interval 95%)
    17.97 (10.87 to 27.17)
    9.23 (5.09 to 17.97)
    Statistical analysis title
    		 Duration of CR Analysis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    28
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.664
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 1.838

    Secondary: Response Rate of Complete Remission (CR)/marrow Complete Remission (mCR)/Partial Remission (PR)/Hematopoietic Improvement (HI))

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    End point title
    		 Response Rate of Complete Remission (CR)/marrow Complete Remission (mCR)/Partial Remission (PR)/Hematopoietic Improvement (HI))
    End point description
    Percentage of complete remission (CR)/marrow Complete Remission (mCR)/partial remission (PR) & Hematological improvement (HI) as per investigator assessment according to IWG-MDS. CR: where the Bone marrow: ≤ 5% blasts with normal maturation of all cell lineages and Peripheral blood: where Hgb ≥ 10 g/dL AND Platelets ≥ 100*109/L AND Neutrophils ≥ 1.0*109/L AND Peripheral blasts 0%. mCR: where the Bone marrow ≤5% blasts and blast count decrease by ≥50% compared to baseline with or without improved blood counts or with or without transfusions. PR: All CR criteria except bone marrow: ≥50% decrease from baseline in blasts in bone marrow AND blast count in bone marrow >5%. HI: restoration or enhancement of the function of the body's blood cell-producing system that must last as least 8 weeks. HI definition is based on modified Hematological Improvement per IWG-MDS criteria in MDS & is the combination of Erythroid response (HI-E), Platelet response (HI-P) & Neutrophil response (HI-N).
    End point type
    Secondary
    End point timeframe
    approx. 32 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Percentage of participants
        number (confidence interval 95%)
    67.7 (54.9 to 78.8)
    61.3 (48.1 to 73.4)
    No statistical analyses for this end point

    Secondary: Percent of Participants who are Red Blood Cells (RBC)/Platelets transfusion independent after randomization as per IWG-MDS

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    End point title
    		 Percent of Participants who are Red Blood Cells (RBC)/Platelets transfusion independent after randomization as per IWG-MDS
    End point description
    Improvement in RBC/platelets transfusion independence. RBC/Platelets transfusion independence rate is defined as the percentage of participants having received no RBC/Platelets transfusions during at least 8 consecutive weeks after randomization.
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Percentage of participants
    number (confidence interval 95%)
        Red blood cells (RBC)
    60.0 (47.1 to 72.0)
    64.5 (51.3 to 76.3)
        Platelets
    73.8 (61.5 to 84.0)
    74.2 (61.5 to 84.5)
    No statistical analyses for this end point

    Secondary: Time to Complete Remission

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    End point title
    		 Time to Complete Remission
    End point description
    Time from randomization to the first documented CR
    End point type
    Secondary
    End point timeframe
    Average of 7 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Months
        median (confidence interval 95%)
    999 (999 to 999)
    999 (999 to 999)
    Statistical analysis title
    		 Time to CR Analyis
    Comparison groups
    MBG453 + hypomethylating agents (HMA) v Placebo + hypomethylating agents (HMA)
    Number of subjects included in analysis
    127
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.237
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.588
         upper limit
    		 2.601

    Secondary: Red Blood Cells (RBC)/Platelets transfusion independence duration after randomization

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    End point title
    		 Red Blood Cells (RBC)/Platelets transfusion independence duration after randomization
    End point description
    The total duration of all transfusion independence periods is the sum of each period of the transfusion independence. RBC/Platelets transfusions independence period is defined as the period for which participants having received no RBC/Platelets transfusions during at least 8 consecutive weeks after randomization.
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    8
    10
    Units: Weeks
    median (inter-quartile range (Q1-Q3))
        RBC
    46.29 (22.86 to 113.00)
    36.71 (20.29 to 65.36)
        Platelets
    44.36 (22.29 to 107.43)
    45.29 (25.14 to 80.00)
    No statistical analyses for this end point

    Secondary: Serum Concentrations for MBG453

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    End point title
    		 Serum Concentrations for MBG453 [1]
    End point description
    Pharmacokinetics (PK) of MBG453 when given in combination with hypomethylating agents (HMA). Cycle - C, Day = D
    End point type
    Secondary
    End point timeframe
    0hr pre-dose on Day 8 of each cycle until cycle 6 and on Day 8 of cycles 9, 12, 18 and 24, 2hr post-dose on Day 8 of C1 and C3, EOT (approx. 48 months) and up to 150 day of the safety follow up period; 1 cycle = 28 days
    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: No statistical analysis was planned for this endpoint
    End point values
    		 MBG453 + hypomethylating agents (HMA)
    Number of subjects analysed
    49
    Units: micro gram/mL
    arithmetic mean (standard deviation)
        C1 D8 at 0 hour (hr) (pre-dose) (n = 47)
    0 ( 0 )
        C1 D8 at 2 hr (n =37)
    103 ( 72.4 )
        C2 D8 at 0 hr (pre-dose) (n = 43)
    38.8 ( 20.5 )
        C3 D8 at 0 hr (pre-dose) (n = 49)
    57.5 ( 32.1 )
        C3 D8 at 2 hr (n = 44)
    149 ( 49.6 )
        C4 D8 at 0 hr (pre-dose) (n = 42)
    70.7 ( 37.6 )
        C5 D8 at 0 hr (pre-dose) (n = 42)
    76.7 ( 38.4 )
        C6 D8 at 0 hr (pre-dose) (n = 39)
    85.0 ( 37.7 )
        C9 D8 at 0 hr (pre-dose) (n = 30)
    97.3 ( 49.3 )
        C12 D8 at 0 hr (pre-dose) (n = 22)
    103 ( 43.0 )
        C18 D8 at 0 hr (pre-dose) (n = 11)
    97.7 ( 42.4 )
        C24 D8 at 0 hr (pre-dose) (n = 4)
    134 ( 39.3 )
        End of treatment (EOT) (n = 40)
    50.0 ( 43.8 )
        30 D Safety follow-up (f/u) (n = 11)
    44.4 ( 46.6 )
        150 D Safety f/u (n = 5)
    0 ( 0 )
    No statistical analyses for this end point

    Secondary: Immunogenicity of MBG453 when given in combination of hypomethylating agents: ADA Incidence

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    End point title
    		 Immunogenicity of MBG453 when given in combination of hypomethylating agents: ADA Incidence [2]
    End point description
    Anti-drug Antibody (ADA) incidence on-treatment. ADA incidence (i.e. ADA-positive subjects) was calculated as the number of subjects with at least 1 on-treatment ADA-positive sample divided by the number of participants with a determinant baseline IG sample and at least one determinant post-baseline IG sample.
    End point type
    Secondary
    End point timeframe
    approx. 48 months
    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: No statistical analysis was planned for this endpoint
    End point values
    		 MBG453 + hypomethylating agents (HMA)
    Number of subjects analysed
    60
    Units: Participants
    6
    No statistical analyses for this end point

    Secondary: Immunogenicity (IG) of MBG453 when given in combination of hypomethylating agents: ADA prevalence

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    End point title
    		 Immunogenicity (IG) of MBG453 when given in combination of hypomethylating agents: ADA prevalence [3]
    End point description
    Number of subjects with at least one sample meeting the criteria either at baseline or post-baseline. Anti-drug Antibody (ADA) prevalence equals ADA-positive at baseline or post-baseline.
    End point type
    Secondary
    End point timeframe
    at baseline
    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: No statistical analysis was planned for this endpoint
    End point values
    		 MBG453 + hypomethylating agents (HMA)
    Number of subjects analysed
    61
    Units: Participants
    11
    No statistical analyses for this end point

    Post-hoc: All Collected Deaths

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    End point title
    		 All Collected Deaths
    End point description
    Deaths were collected from randomization until end of trial, approx. 48 months.
    End point type
    Post-hoc
    End point timeframe
    from randomization until end of trial, approx. 48 months
    End point values
    		 MBG453 + hypomethylating agents (HMA) Placebo + hypomethylating agents (HMA)
    Number of subjects analysed
    65
    62
    Units: Participants
        Pre-treatment deaths
    0
    1
        On-treatment deaths
    5
    13
        Post-treatment deaths
    40
    39
        Total deaths
    45
    53
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were collected from the date of 1st administration of study treatment to 30 days after the date of the last administration of study treatment, up to approx. 48 months. Deaths were collected from randomization until end of trial, approx. 48 months
    Adverse event reporting additional description
    Adverse Event: Any sign or symptom that occurs during the study treatment + 30 days post treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    Placebo + hypomethylating agents (HMA)
    Reporting group description
    		 Patients are taking placebo plus hypomethylating agents

    Reporting group title
    MBG453 + hypomethylating agents (HMA)
    Reporting group description
    		 Patients are taking MBG453 plus hypomethylating agents

    Serious adverse events
    		 Placebo + hypomethylating agents (HMA) MBG453 + hypomethylating agents (HMA)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 63 (68.25%)
    38 / 62 (61.29%)
         number of deaths (all causes)
    53
    45
         number of deaths resulting from adverse events
    2
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to bone
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip squamous cell carcinoma
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the hypopharynx
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Death
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Condition aggravated
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chills
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    9 / 63 (14.29%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    1 / 11
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Immune reconstitution inflammatory syndrome
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary hypertension
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Pleural effusion
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Organising pneumonia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    General physical condition abnormal
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Haemoglobin decreased
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    White blood cell count decreased
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile nonhaemolytic transfusion reaction
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dysarthria
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    3 / 63 (4.76%)
    3 / 62 (4.84%)
         occurrences causally related to treatment / all
    2 / 3
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperleukocytosis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    14 / 63 (22.22%)
    16 / 62 (25.81%)
         occurrences causally related to treatment / all
    10 / 22
    11 / 19
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    2 / 63 (3.17%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal disorders
    Gastric haemorrhage
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophilic dermatosis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Epiglottitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    3 / 63 (4.76%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 63 (1.59%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 63 (3.17%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Encephalitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dermo-hypodermitis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingival abscess
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella bacteraemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    11 / 63 (17.46%)
    9 / 62 (14.52%)
         occurrences causally related to treatment / all
    5 / 15
    5 / 14
         deaths causally related to treatment / all
    1 / 4
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonal bacteraemia
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary tuberculosis
         subjects affected / exposed
    2 / 63 (3.17%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 63 (1.59%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    8 / 63 (12.70%)
    4 / 62 (6.45%)
         occurrences causally related to treatment / all
    1 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Septic shock
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 62 (3.23%)
         occurrences causally related to treatment / all
    1 / 4
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 63 (1.59%)
    3 / 62 (4.84%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    2 / 63 (3.17%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal bacterial infection
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 63 (0.00%)
    1 / 62 (1.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 63 (1.59%)
    0 / 62 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo + hypomethylating agents (HMA) MBG453 + hypomethylating agents (HMA)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    63 / 63 (100.00%)
    61 / 62 (98.39%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    7 / 63 (11.11%)
    7 / 62 (11.29%)
         occurrences all number
    13
    7
    Haematoma
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 62 (6.45%)
         occurrences all number
    4
    4
    Hypotension
         subjects affected / exposed
    6 / 63 (9.52%)
    3 / 62 (4.84%)
         occurrences all number
    9
    3
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    7 / 63 (11.11%)
    11 / 62 (17.74%)
         occurrences all number
    8
    21
    Chest pain
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 62 (3.23%)
         occurrences all number
    5
    2
    Fatigue
         subjects affected / exposed
    8 / 63 (12.70%)
    14 / 62 (22.58%)
         occurrences all number
    8
    18
    Injection site erythema
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 62 (3.23%)
         occurrences all number
    4
    2
    Injection site reaction
         subjects affected / exposed
    10 / 63 (15.87%)
    4 / 62 (6.45%)
         occurrences all number
    12
    7
    Oedema
         subjects affected / exposed
    5 / 63 (7.94%)
    3 / 62 (4.84%)
         occurrences all number
    5
    3
    Oedema peripheral
         subjects affected / exposed
    7 / 63 (11.11%)
    8 / 62 (12.90%)
         occurrences all number
    7
    10
    Pain
         subjects affected / exposed
    4 / 63 (6.35%)
    3 / 62 (4.84%)
         occurrences all number
    4
    3
    Pyrexia
         subjects affected / exposed
    13 / 63 (20.63%)
    17 / 62 (27.42%)
         occurrences all number
    17
    27
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    3 / 63 (4.76%)
    5 / 62 (8.06%)
         occurrences all number
    5
    7
    Cough
         subjects affected / exposed
    11 / 63 (17.46%)
    8 / 62 (12.90%)
         occurrences all number
    14
    9
    Dyspnoea
         subjects affected / exposed
    12 / 63 (19.05%)
    11 / 62 (17.74%)
         occurrences all number
    12
    13
    Epistaxis
         subjects affected / exposed
    6 / 63 (9.52%)
    8 / 62 (12.90%)
         occurrences all number
    10
    9
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    9 / 63 (14.29%)
    9 / 62 (14.52%)
         occurrences all number
    10
    9
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    12 / 63 (19.05%)
    4 / 62 (6.45%)
         occurrences all number
    18
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    9 / 63 (14.29%)
    6 / 62 (9.68%)
         occurrences all number
    14
    7
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 62 (6.45%)
         occurrences all number
    4
    4
    Blood bilirubin increased
         subjects affected / exposed
    5 / 63 (7.94%)
    1 / 62 (1.61%)
         occurrences all number
    8
    1
    Blood creatinine increased
         subjects affected / exposed
    5 / 63 (7.94%)
    2 / 62 (3.23%)
         occurrences all number
    10
    2
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    5 / 63 (7.94%)
    3 / 62 (4.84%)
         occurrences all number
    7
    3
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    7 / 63 (11.11%)
    2 / 62 (3.23%)
         occurrences all number
    8
    2
    Lymphocyte count decreased
         subjects affected / exposed
    5 / 63 (7.94%)
    3 / 62 (4.84%)
         occurrences all number
    27
    13
    Neutrophil count decreased
         subjects affected / exposed
    23 / 63 (36.51%)
    14 / 62 (22.58%)
         occurrences all number
    89
    55
    Platelet count decreased
         subjects affected / exposed
    19 / 63 (30.16%)
    12 / 62 (19.35%)
         occurrences all number
    70
    17
    SARS-CoV-2 test negative
         subjects affected / exposed
    7 / 63 (11.11%)
    5 / 62 (8.06%)
         occurrences all number
    9
    13
    Weight decreased
         subjects affected / exposed
    8 / 63 (12.70%)
    10 / 62 (16.13%)
         occurrences all number
    12
    10
    White blood cell count decreased
         subjects affected / exposed
    17 / 63 (26.98%)
    13 / 62 (20.97%)
         occurrences all number
    54
    34
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 63 (0.00%)
    6 / 62 (9.68%)
         occurrences all number
    0
    6
    Procedural pain
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 62 (6.45%)
         occurrences all number
    0
    4
    Transfusion reaction
         subjects affected / exposed
    5 / 63 (7.94%)
    2 / 62 (3.23%)
         occurrences all number
    9
    2
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    4 / 63 (6.35%)
    0 / 62 (0.00%)
         occurrences all number
    4
    0
    Atrial fibrillation
         subjects affected / exposed
    2 / 63 (3.17%)
    5 / 62 (8.06%)
         occurrences all number
    2
    5
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    5 / 63 (7.94%)
    8 / 62 (12.90%)
         occurrences all number
    7
    13
    Headache
         subjects affected / exposed
    7 / 63 (11.11%)
    8 / 62 (12.90%)
         occurrences all number
    7
    12
    Paraesthesia
         subjects affected / exposed
    0 / 63 (0.00%)
    4 / 62 (6.45%)
         occurrences all number
    0
    5
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    32 / 63 (50.79%)
    22 / 62 (35.48%)
         occurrences all number
    70
    36
    Thrombocytopenia
         subjects affected / exposed
    13 / 63 (20.63%)
    20 / 62 (32.26%)
         occurrences all number
    24
    44
    Neutropenia
         subjects affected / exposed
    20 / 63 (31.75%)
    25 / 62 (40.32%)
         occurrences all number
    105
    104
    Febrile neutropenia
         subjects affected / exposed
    9 / 63 (14.29%)
    11 / 62 (17.74%)
         occurrences all number
    12
    21
    Eye disorders
    Conjunctival haemorrhage
         subjects affected / exposed
    5 / 63 (7.94%)
    1 / 62 (1.61%)
         occurrences all number
    5
    1
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    2 / 63 (3.17%)
    4 / 62 (6.45%)
         occurrences all number
    2
    6
    Vomiting
         subjects affected / exposed
    6 / 63 (9.52%)
    7 / 62 (11.29%)
         occurrences all number
    7
    10
    Toothache
         subjects affected / exposed
    2 / 63 (3.17%)
    4 / 62 (6.45%)
         occurrences all number
    2
    5
    Stomatitis
         subjects affected / exposed
    9 / 63 (14.29%)
    4 / 62 (6.45%)
         occurrences all number
    11
    9
    Haemorrhoids
         subjects affected / exposed
    6 / 63 (9.52%)
    6 / 62 (9.68%)
         occurrences all number
    6
    9
    Diarrhoea
         subjects affected / exposed
    15 / 63 (23.81%)
    27 / 62 (43.55%)
         occurrences all number
    22
    42
    Constipation
         subjects affected / exposed
    26 / 63 (41.27%)
    29 / 62 (46.77%)
         occurrences all number
    41
    61
    Abdominal pain
         subjects affected / exposed
    5 / 63 (7.94%)
    5 / 62 (8.06%)
         occurrences all number
    5
    6
    Nausea
         subjects affected / exposed
    19 / 63 (30.16%)
    15 / 62 (24.19%)
         occurrences all number
    39
    26
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    7 / 63 (11.11%)
    11 / 62 (17.74%)
         occurrences all number
    7
    23
    Night sweats
         subjects affected / exposed
    2 / 63 (3.17%)
    6 / 62 (9.68%)
         occurrences all number
    4
    6
    Erythema
         subjects affected / exposed
    2 / 63 (3.17%)
    6 / 62 (9.68%)
         occurrences all number
    3
    20
    Rash
         subjects affected / exposed
    8 / 63 (12.70%)
    12 / 62 (19.35%)
         occurrences all number
    11
    15
    Purpura
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 62 (3.23%)
         occurrences all number
    5
    2
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    3 / 63 (4.76%)
    5 / 62 (8.06%)
         occurrences all number
    3
    5
    Dysuria
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 62 (6.45%)
         occurrences all number
    3
    7
    Haematuria
         subjects affected / exposed
    3 / 63 (4.76%)
    4 / 62 (6.45%)
         occurrences all number
    6
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    8 / 63 (12.70%)
    8 / 62 (12.90%)
         occurrences all number
    10
    11
    Back pain
         subjects affected / exposed
    7 / 63 (11.11%)
    12 / 62 (19.35%)
         occurrences all number
    7
    14
    Myalgia
         subjects affected / exposed
    1 / 63 (1.59%)
    6 / 62 (9.68%)
         occurrences all number
    1
    10
    Pain in extremity
         subjects affected / exposed
    6 / 63 (9.52%)
    11 / 62 (17.74%)
         occurrences all number
    8
    12
    Infections and infestations
    COVID-19
         subjects affected / exposed
    4 / 63 (6.35%)
    9 / 62 (14.52%)
         occurrences all number
    4
    10
    Cellulitis
         subjects affected / exposed
    4 / 63 (6.35%)
    3 / 62 (4.84%)
         occurrences all number
    5
    3
    Nasopharyngitis
         subjects affected / exposed
    5 / 63 (7.94%)
    0 / 62 (0.00%)
         occurrences all number
    5
    0
    Oral herpes
         subjects affected / exposed
    6 / 63 (9.52%)
    3 / 62 (4.84%)
         occurrences all number
    6
    3
    Pneumonia
         subjects affected / exposed
    7 / 63 (11.11%)
    2 / 62 (3.23%)
         occurrences all number
    8
    3
    Respiratory tract infection
         subjects affected / exposed
    0 / 63 (0.00%)
    5 / 62 (8.06%)
         occurrences all number
    0
    6
    Urinary tract infection
         subjects affected / exposed
    3 / 63 (4.76%)
    9 / 62 (14.52%)
         occurrences all number
    5
    27
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    6 / 63 (9.52%)
    13 / 62 (20.97%)
         occurrences all number
    6
    14
    Hyperglycaemia
         subjects affected / exposed
    9 / 63 (14.29%)
    4 / 62 (6.45%)
         occurrences all number
    23
    7
    Hyperkalaemia
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 62 (3.23%)
         occurrences all number
    9
    2
    Hypernatraemia
         subjects affected / exposed
    4 / 63 (6.35%)
    2 / 62 (3.23%)
         occurrences all number
    9
    2
    Hyperuricaemia
         subjects affected / exposed
    2 / 63 (3.17%)
    4 / 62 (6.45%)
         occurrences all number
    2
    5
    Hypoalbuminaemia
         subjects affected / exposed
    5 / 63 (7.94%)
    6 / 62 (9.68%)
         occurrences all number
    8
    6
    Hypocalcaemia
         subjects affected / exposed
    4 / 63 (6.35%)
    1 / 62 (1.61%)
         occurrences all number
    9
    1
    Hypokalaemia
         subjects affected / exposed
    13 / 63 (20.63%)
    12 / 62 (19.35%)
         occurrences all number
    16
    17
    Hypomagnesaemia
         subjects affected / exposed
    4 / 63 (6.35%)
    1 / 62 (1.61%)
         occurrences all number
    4
    1
    Hyponatraemia
         subjects affected / exposed
    8 / 63 (12.70%)
    4 / 62 (6.45%)
         occurrences all number
    12
    4

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Apr 2019
    To add a general guideline for dosing modifications of the investigational drug (sabatolimab/placebo) in relation to nonhematologic non-immune-related toxicities that were clinically significant according to the Investigator and possibly attributable to the investigational drug. This guideline did not apply to nonhematologic non-immune-related toxicities that were attributable to decitabine/azacitidine or the MDS and its complications.
    13 Jan 2020
    The primary purpose of this amendment was to address Health Authorities’ requests and SSC recommendations. Based on FDA feedback, EFS was added as a secondary endpoint, defined similarly to the EFS definition used for AML. Events included failure to achieve complete remission within the first 6 months, relapse from complete remission, or death from any cause, whichever occurred first. PK and IG sample collection were extended, with updated time points. The SSC recommended prohibiting the use of erythropoietin-stimulating agents and thrombopoietic agents during the study, as they could mask cytopenias. However, GCSF was not prohibited because it was part of the standard care in cases of infection or septicemia. The table for CR was updated accordingly; Confirmation of CR by peripheral blood at 4 weeks was removed. CR was considered confirmed if progression or relapse from CR was not observed within 4 weeks. Assessment of hematological improvements based on IWG 2006 criteria were added, and definitions of transfusion independence/dependence status were adapted to reflect the IWG 2018 criteria. Reference values to determine significant increases in blasts or decreases in blood values were added. The inclusion criterion for adequate renal function was updated to use the MDRD formula instead of the Cockcroft-Gault formula, as MDRD is more accurate below an eGFR of 60 mm/min/1.73 m² and better suited for identifying renal impairment in the older MDS population (median age around 70 years). The exclusion criterion related to previous cancer was clarified to specify that low-risk MDS subjects who adequately treated with lenalidomide and failed were eligible. Lenalidomide was not to be administered for intermediate, high, or very high-risk MDS. The safety information was updated to align with the Investigator Brochure Edition 5.1. Clarifications and corrections were made throughout the protocol, along with editorial changes to improve flow and consistency.
    06 May 2020
    The purpose of this amendment was to update the definitions of the RBC or platelet transfusion dependence and transfusion independence in Section 8.3, Table 8-2 based on FDA feedback. The same pre-specified period of observation (i.e. 8 weeks) was used to determine the transfusion status throughout the study. The interval of 8 weeks was selected, as it was in line with the assessment of transfusions for hematologic improvement and was acceptable to evaluate the transfusion status of high-risk MDS subjects at baseline. Transfusion independence was defined as absence of any transfusion during a given period of observation.
    02 Sep 2021
    The main purpose of this amendment was to clarify that long-term safety and efficacy data is collected until 4 years after last subject was randomized, which is the time of the end of study and the data cut-off date for the final OS analysis. Further, based on the observed pooled PFS events, the pooled rate of discontinuations without PFS event, the limited number of subjects that are still at risk to have a PFS event and the predictions of future PFS events, the target number of PFS events for the final PFS analysis might not be reached at all or within a reasonable time frame. Thus, the final PFS analysis data cut-off date is now planned to be approximately 4 months after the interim PFS (iPFS) analysis data cut-off date (or after approximately 108 PFS events are observed if this is earlier) if PFS is not already significant at iPFS analysis. The final PFS analysis if applicable, and the interim OS analysis will be performed approximately 4 months after the iPFS analysis data cut-off date. Based on FDA’s recommendation, the alpha spending function for PFS and OS analyses were modified to use O’Brien and Fleming boundaries. Post Trial Access (PTA) language was included to clarify the provision of study treatment to trial subjects who complete participation in this trial and continue to derive clinical benefit from the treatment based on the Investigator’s evaluation. Furthermore, new Novartis standard language, referred to as disruption proofing language, has been added to specify trial conduct during public health emergencies. The added language addresses study subject safety and trial integrity. Additional guidance for COVID-19 vaccinations was added to avoid overlapping adverse events with study treatment including update on risk and benefits session. Lastly, the definition of withdrawal of consent and management of biological samples was updated as per latest protocol template.

    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.
    127 subjects were randomized. However, only 125 were treated. 2 subjs in S+HMA arm received only HMA & were reported in P+HMA arm in the safety dataset. Therefore, the safety dataset included 62 subjs in the S+HMA arm & 63 subjects in the P+HMA arm.
    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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