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    Clinical Trial Results:
    Efficacy and Safety of Eltrombopag in Patients with Acquired Moderate Aplastic Anemia (EMAA) who are treated with Ciclosporin A Prospective Randomized Multicenter Study comparing Thrombopoetin-Receptor agonist Eltrombopagwith Placebo in Patients with Acquired Moderate Aplastic Anemia who are treated with Ciclosporin A

    Summary
    EudraCT number
    		 2014-000174-19
    Trial protocol
    		 DE   FR  
    Global end of trial date
    23 Dec 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Feb 2026
    First version publication date
    14 Feb 2026
    Other versions
    Summary report(s)
    		 CSR_EMAA-trial
    Patient characteristics EMAA-trial
    SAE_listing_EMAA-trial
    AE_listing_EMAAtrial

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EMAA study / 9345
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02773225
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Universitätsklinikum Ulm
    Sponsor organisation address
    Albert-Einstein-Allee 29, Ulm, Germany, 89081
    Public contact
    Britta Höchsmann, Universitätsklinikum Ulm, 0049 731150560, b.hoechsmann@blutspende.de
    Scientific contact
    Britta Höchsmann, Universitätsklinikum Ulm, 0049 731150560, b.hoechsmann@blutspende.de
    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
    08 Jan 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Dec 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Dec 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The aim of this trial is to improve treatment of Moderate Aplastic Anemia (MAA) by evaluating the safety and efficiency of Eltrombopag as a new treatment option in patients with MAA requiring therapy. The primary objective of this trial is the evaluation of the superiority of Eltrombopag on top of background treatment with Ciclosporin (CSA) regarding hematologic response (PR +CR) at 6 months in comparison with treatment with CSA alone in untreated MAA patient.
    Protection of trial subjects
    In general examinations (especially bone marrow punctures) was reduced to as few as possible to minimize pain and distress of the patients. For early detection of patient complaints patient diary and quality of life questionnaires was usedin a regular manner. Safety assessment before start and during therapy were: • collection of demographic data and medical history • complete physical examination • Full blood count with WBC differential and microscopic peripheral blood count • Reticulocyte count • blood samples for blood chemistry and coagulation profile: creatinine, urea, uric acid, glucose, LDH, AST, ALT, y-GT, AP, protein, bilirubin (direct and total), INR, PTT, CSA trough level - blood samples for GPI-deficiency • bone marrow histology and cytology, cytogenetics • Quality of Life instruments • ophtalmologic examination (cataract) • electrocardiogram, QT-time • in female patients of childbearing potential, a pregnancy test has to be performed with a negative result before inclusion in the study • pregnancy test may be repeated at each visit within the discretion of the investigator These investigations were conducted because they enable the early detection of possible adverse events caused by the study or background therapy or the disease itself. Suspected adverse events of Eltrombopag are hepatotoxicity, thrombotic/thromboembolic complications, cataract, bleeding after discontinuation of Eltrombopag, bone marrow reticulin formation, risk of bone marrow fibrosis, malignancies. Suspected adverse events due to aplastic anemia are cytopenias with clinical symptoms like bleedings, infections, anemia and clonal evolution. Suspected adverse events due to CSA are renal dysfunction, hypertension, hepatoxicity, neurotoxicity, skin abnormalities, hirsutism, gum hyperplasia, malignancies, infections, hypomagnesemia and hyperkalemia, increases in uric acid, dose related hyperbilirubinemia, modest increase of serum triglycerides or cholesterol.
    Background therapy
    		 Cyclosporin A
    Evidence for comparator
    		 Eltrombopag is an oral thrombopoietin mimetic that binds to c-MPL, promoting mega-karyopoiesis and release of platelets from mature megakaryocytes and has been approved for SAA refractory to immunosuppressive therapy by the Food and Drug Administration (FDA) in 2014 and the European Medicines Agency (EMA) in 2015. This decision was based on long-term data regarding to safety and efficacy of a phase II study in SAA patients. This data raises also the hope for thrombopoetin as an effective new therapeutic option in patients with MAA. We hypothesize that there might be a higher rate of patients responding to Eltrombopag in a group of therapy naïve AA patients, especially in MAA. Furthermore, we assume that the addition of Eltrombopag to the routinely used immunosuppression CSA might lead to a further increase of the remission rates. Thus, we see a strong need for more data regarding efficacy and tolerability of Eltrombopag in Aplastic Anemia in order to clarify the role of Eltrombopag within standard treatment of Aplastic Anemia, especially in Moderate Aplastic Anemia. Therefore, we considered a blinded comparison between immunosuppressive therapy (CSA + placebo) and the addition of eltrombopag to immunosuppressive therapy (CSA + eltrombopag) to be logical for improving the treatment of MAA patients. In the meantime data of a combination therapy with intensified immunosuppressive therapy (hATG + CSA) and eltrombopag in first line therapy of SAA and VSAA without the option of SCT show a significant benefit for the addition of Eltrombopag to the immunosuppressive therapy without an increase of adverse events. Based on this data Eltrombopag was approved in 2018 by the FDA for the first line treatment of SAA/VSAA in combination with intensified immunosuppressive therapy, which supported our approach
    Actual start date of recruitment
    01 May 2015
    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
    Switzerland: 6
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Germany: 78
    Worldwide total number of subjects
    85
    EEA total number of subjects
    79
    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)
    59
    From 65 to 84 years
    26
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Between 27 May 2015 (First patient first visit (FPFV)) and 09 May 2023 (Last patient first visit (LPFV)) ninety-three (93) patients were enrolled and screened at nine study centers in three countries (France, Germany, Switzerland). 85 patients successfully completed screening and were randomized to one of the two treatment arms.

    Pre-assignment
    Screening details
    		 93 patients were screened , 8 were not eligible, 7 because of violation of the inclusion exclusion criteria, in one case the cause is missing

    Pre-assignment period milestones
    Number of subjects started
    		 85
    Number of subjects completed
    		 85

    Period 1
    Period 1 title
    Blinded Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer
    Blinding implementation details
    On receipt of the patient registration and randomization form, the patient data were entered in the Electronic Trial Data Base (eCRF). The assignment to either the standard (placebo) or the investigational treatment (eltrombopag) was done by an independent data manager to guarantee that the randomization was separated from the clinical investigators. The ratio of patients included in each arm for placebo versus eltrombopag treatment was 1:1.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Verum
    Arm description
    		 Eltrombopag (150 mg) treatment + background therapy with CSA
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eltrombopag 75 mg Tabletten
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg (2 x 75 mg) once daily

    Arm title
    		 Placebo
    Arm description
    		 placebo treatment
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo Tablet
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2 tablets once daily

    Number of subjects in period 1
    		Verum Placebo
    Started
    41
    44
    Primary endpoint reached, unblinding
    35
    40
    Completed
    35
    40
    Not completed
    6
    4
         Consent withdrawn by subject
    1
    -
         Adverse event, non-fatal
    1
    -
         reason unknonw
    2
    -
         completion per protocol
    1
    -
         Unknown reason
    -
    1
         Progressive disease
    -
    3
         disease progression
    1
    -
    Period 2
    Period 2 title
    Unblinded period
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 A: Placebo, no CR
    Arm description
    		 Patient received background therapy with CSA and Placebo in the blinded period and had no CR (complete remission) at the primary endpoint.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Eltrombopag 75 mg Tabletten
    Investigational medicinal product code
    Verum, Eltrombopag
    Other name
    EU/1/10/612/013 Revolade® 75 mg
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg (2 x 75 mg) once daily

    Arm title
    		 Arm B: Placebo and CR
    Arm description
    		 Arm B: Placebo + Background Therapy (CSA) during blinded period with CR at primary endpoint. No further study treatment after unblinding.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Arm C: Eltrombopag and PR/CR
    Arm description
    		 Arm C Patients with Eltrombopag and background therapy in the blinded period and responde with complete or partial remission (PR/CR) at the primary endpoint. Further eltrombopag treatment according the protocoll.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Eltrombopag 75 mg Tabletten
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg (2 x 75 mg) once daily

    Arm title
    		 Arm D: Eltrombopag and non response (NR)
    Arm description
    		 Arm D: patients received Eltrombopag and background therapy during the blinded period. At primary endpoint no response. Stop of study treatment and further therapy according to the decision of the treating phycisian
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 2
    		A: Placebo, no CR Arm B: Placebo and CR Arm C: Eltrombopag and PR/CR Arm D: Eltrombopag and non response (NR)
    Started
    38
    2
    26
    9
    Completed
    20
    1
    20
    5
    Not completed
    18
    1
    6
    4
         Adverse event, serious fatal
    -
    -
    -
    1
         Consent withdrawn by subject
    2
    -
    -
    1
         Physician decision
    3
    -
    1
    -
         per protocol
    -
    -
    -
    1
         completion per protocol
    7
    -
    3
    -
         Unknown reason
    4
    -
    1
    1
         Lost to follow-up
    2
    1
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Verum
    Reporting group description
    		 Eltrombopag (150 mg) treatment + background therapy with CSA

    Reporting group title
    Placebo
    Reporting group description
    		 placebo treatment

    Reporting group values
    		 Verum Placebo Total
    Number of subjects
    		 41 44 85
    Age categorical
    The median age of patients was 53 years (range 19-84 years) with 37.6% of them being older than 60 years. Since age plays an important role in the response to therapy for aplastic anemia, it was important for us to ensure a balanced age distribution between the verum and placebo groups during randomization.
    Units: Subjects
        Adults (18-64 years)
    		 29 30 59
        From 65-84 years
    		 12 14 26
        85 years and over
    		 0 0 0
    Gender categorical
    40 patients were female
    Units: Subjects
        Female
    		 18 22 40
        Male
    		 23 22 45

    End points

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    End points reporting groups
    Reporting group title
    Verum
    Reporting group description
    		 Eltrombopag (150 mg) treatment + background therapy with CSA

    Reporting group title
    Placebo
    Reporting group description
    		 placebo treatment
    Reporting group title
    A: Placebo, no CR
    Reporting group description
    		 Patient received background therapy with CSA and Placebo in the blinded period and had no CR (complete remission) at the primary endpoint.

    Reporting group title
    Arm B: Placebo and CR
    Reporting group description
    		 Arm B: Placebo + Background Therapy (CSA) during blinded period with CR at primary endpoint. No further study treatment after unblinding.

    Reporting group title
    Arm C: Eltrombopag and PR/CR
    Reporting group description
    		 Arm C Patients with Eltrombopag and background therapy in the blinded period and responde with complete or partial remission (PR/CR) at the primary endpoint. Further eltrombopag treatment according the protocoll.

    Reporting group title
    Arm D: Eltrombopag and non response (NR)
    Reporting group description
    		 Arm D: patients received Eltrombopag and background therapy during the blinded period. At primary endpoint no response. Stop of study treatment and further therapy according to the decision of the treating phycisian

    Primary: change in measure response between time point Baseline and time point 6 months'

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    End point title
    		 change in measure response between time point Baseline and time point 6 months'
    End point description
    Assessment of hematologic response after 6 months prior to unblinding. The primary objective of this trial is the evaluation of the superiority of Eltrombopag on top of background treatment with Ciclosporin (CSA) regarding hematologic response (PR + CR) at 6 months in comparison with treatment with CSA alone in untreated MAA patient. The primary endpoint of the study is the hematologic response rate (CR + PR) at 6 months.
    End point type
    Primary
    End point timeframe
    Response-rate after 6 months after start of study treatment
    End point values
    		 Verum Placebo
    Number of subjects analysed
    35
    40
    Units: percent
        arithmetic mean (confidence interval 95%)
    71.4 (54.8 to 83.8)
    42.5 (28.5 to 57.8)
    Attachments
    		 Response Rate 6 months
    Statistical analysis title
    		 Response rate at 6 months
    Statistical analysis description
    Chi-square test was used to compare categorical variables and the Mann-Whitney U test (nonparametric) or student t-test (parametric) to compare continuous variables. The probability of survival was analyzed using the method of Kaplan and Meier and log rank test. Cumulative incidences were estimated by the multi-stage method by Aalen-Johansen and compared between treatment arms by cox regression. A logistic regression of binary outcomes provided results with respect to the relevant covariate
    Comparison groups
    Verum v Placebo
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.05 [2]
    Method
    		 Fisher exact
    Parameter type
    		 Cox regression
    Point estimate
    95
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 95
         upper limit
    		 -
    Variability estimate
    Standard deviation
    Dispersion value
    5
    Notes
    [1] - analysis of primary endpoint based on PPS. Absolute and relative frequency of patients with response (CR or PR) will be derived by treatment arm. Let the counts in the true population denote (Treatment Response: Yes - No; Eltrombopag: n11 - n12; Placebo: n21-n22. If the hematological response is independent of the treatment arm the odds ratio (OR=n11*n22/(n12*n21).) will be 1. Thus, Fisher’s exact test may be interpreted as a test of the OR and is suitable for comparing the frequenc
    [2] - P-values ≥ 0.001 reported to 3 decimal places; p-values < 0.001 reported as “< 0.001”. Mean, standard deviation and any quantiles other than minimum and maximum, reported to one decimal place greater than the original data.

    Secondary: change in measure response between time point Baseline and time point 3 months'

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    End point title
    		 change in measure response between time point Baseline and time point 3 months'
    End point description
    The secondary objective of this trial is to investigate the impact of Eltrombopag added to background therapy with CSA. Secondary endpoints are: • Response rate at 3 months
    End point type
    Secondary
    End point timeframe
    Change in response rate between start of study treatment and 3 months
    End point values
    		 Verum Placebo
    Number of subjects analysed
    41
    44
    Units: percent
        arithmetic mean (confidence interval 95%)
    48.8 (34.3 to 63.5)
    25.0 (14.4 to 39.6)
    Attachments
    		 Response 3 months
    Statistical analysis title
    		 Response rate
    Comparison groups
    Verum v Placebo
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.05
    Method
    		 Chi-squared
    Parameter type
    		 Cox proportional hazard
    Point estimate
    95
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 95
         upper limit
    		 -
    Variability estimate
    Standard deviation
    Dispersion value
    5

    Secondary: change in measure response between time point Baseline and time point 12 months'

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    End point title
    		 change in measure response between time point Baseline and time point 12 months'
    End point description
    change in measure response between time point Baseline and time point 12 months
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 A: Placebo, no CR Arm B: Placebo and CR Arm C: Eltrombopag and PR/CR Arm D: Eltrombopag and non response (NR)
    Number of subjects analysed
    38
    2
    26
    9
    Units: percent
        number (not applicable)
    65.8
    50.0
    88.5
    22.2
    Attachments
    		 Response rate after 12 months
    Statistical analysis title
    		 Response Rate at 12 months
    Statistical analysis description
    change in measure response between time point Baseline and time point 12 months'
    Comparison groups
    A: Placebo, no CR v Arm B: Placebo and CR v Arm C: Eltrombopag and PR/CR v Arm D: Eltrombopag and non response (NR)
    Number of subjects included in analysis
    75
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Cox regression
    Point estimate
    95
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 95
         upper limit
    		 -
    Variability estimate
    Standard deviation
    Dispersion value
    5

    Secondary: change in measure response between time point Baseline and time point 18 months'

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    End point title
    		 change in measure response between time point Baseline and time point 18 months'
    End point description
    The response assessment will be calculated as defined by the response criteria according to the protocol. Additionally, the investigator will classify hematologic response. Both assessments will be evaluated descriptively, but the calculated assessment will be prevailing for hypothesis testing. Proportions of hematological response (CR +PR) will be estimated 18 months after therapy start for each group and study arm. Withdrawals and dropouts in the preceding period since last response assessment will be listed in the descriptive table as “missing response”. A comparison between treatment arms (Placebo and Eltrombopag) will be performed after 3, 12 and 18 months after therapy start.
    End point type
    Secondary
    End point timeframe
    18 months
    End point values
    		 A: Placebo, no CR Arm B: Placebo and CR Arm C: Eltrombopag and PR/CR Arm D: Eltrombopag and non response (NR)
    Number of subjects analysed
    27
    2
    22
    5
    Units: percent
        number (not applicable)
    62.1
    50.0
    65.4
    11.1
    Attachments
    		 Response Rate 18 months
    Statistical analysis title
    		 Response rate after 18 months
    Comparison groups
    A: Placebo, no CR v Arm B: Placebo and CR v Arm C: Eltrombopag and PR/CR v Arm D: Eltrombopag and non response (NR)
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.05
    Method
    		 Fisher exact
    Parameter type
    		 Cox regression
    Point estimate
    95
    Confidence interval
         level
    		 95%
         sides
    1-sided
         lower limit
    		 95
         upper limit
    		 -
    Variability estimate
    Standard deviation
    Dispersion value
    5

    Secondary: change in measure relapse between time point Baseline and time point 6 months

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    End point title
    		 change in measure relapse between time point Baseline and time point 6 months
    End point description
    Clinical relapse is considered as the occurrence of any of the following events in a patient who had shown a hematological response (CR or PR or single lineage response): • meeting again the criteria for MAA •renewed transfusion requirement •decrease in any of the responded peripheral blood counts to the pre-study baseline Patients who withdrew consent or dropped out after hematological response before the respective visit will be counted as “missing” in descriptive tables. Proportions of relapse will be estimated at 6, 12 and 18 months per treatment arm / group. 95% confidence limits according to Agresti and Coull for the proportions of relapse will be computed. Only after 6 months from therapy start, the null hypothesis that the OR is 1 will be assessed by Fisher’s exact test. The hypothesis will be tested against two-sided alternative at the 5% level of significance
    End point type
    Secondary
    End point timeframe
    from baseline to 6 months evaluation
    End point values
    		 Verum Placebo
    Number of subjects analysed
    35
    40
    Units: percent
        arithmetic mean (confidence interval 95%)
    16.7 (6.9 to 34.0)
    0 (0 to 0)
    Attachments
    		 Relapse Rate 6 months
    No statistical analyses for this end point

    Secondary: change in measure relapse between time point Baseline and time point 12 months

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    End point title
    		 change in measure relapse between time point Baseline and time point 12 months
    End point description
    Clinical relapse is considered as the occurrence of any of the following events in a patient who had shown a hematological response (CR or PR or single lineage response): • meeting again the criteria for MAA •renewed transfusion requirement •decrease in any of the responded peripheral blood counts to the pre-study baseline. Proportions of relapse will be estimated at 6, 12 and 18 months per treatment arm / group. 95% confidence limits according to Agresti and Coull for the proportions of relapse will be computed. Only after 6 months from therapy start, the null hypothesis that the OR is 1 will be assessed by Fisher’s exact test. The hypothesis will be tested against two-sided alternative at the 5% level of significance. A 95% confidence interval for the OR will be provided. A cox regression will be performed to quantify the relationship between relapse and total dose of Eltrombopag administered. “Age” and “disease severity” will be included in the regression model.
    End point type
    Secondary
    End point timeframe
    12 months
    End point values
    		 A: Placebo, no CR Arm B: Placebo and CR Arm C: Eltrombopag and PR/CR
    Number of subjects analysed
    38
    2
    26
    Units: percent
        arithmetic mean (confidence interval 95%)
    10.7 (2.9 to 28.0)
    50.0 (9.5 to 90.5)
    38.5 (22.4 to 57.5)
    Attachments
    		 Relapse Rate
    No statistical analyses for this end point

    Secondary: change in measure relapse between time point Baseline and time point 18 months

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    End point title
    		 change in measure relapse between time point Baseline and time point 18 months
    End point description
    Clinical relapse is considered as the occurrence of any of the following events in a patient who had shown a hematological response (CR or PR or single lineage response): • meeting again the criteria for MAA •renewed transfusion requirement •decrease in any of the responded peripheral blood counts to the pre-study baseline Patients who withdrew consent or dropped out after hematological response before the respective visit will be counted as “missing” in descriptive tables. Proportions of relapse will be estimated at 6, 12 and 18 months per treatment arm / group. 95% confidence limits according to Agresti and Coull for the proportions of relapse will be computed. Only after 6 months from therapy start, the null hypothesis that the OR is 1 will be assessed by Fisher’s exact test. The hypothesis will be tested against two-sided alternative at the 5% level of significance
    End point type
    Secondary
    End point timeframe
    18 months
    End point values
    		 A: Placebo, no CR Arm B: Placebo and CR Arm C: Eltrombopag and PR/CR
    Number of subjects analysed
    27
    2
    22
    Units: percent
        arithmetic mean (confidence interval 95%)
    34.6 (19.3 to 53.9)
    50.0 (9.5 to 90.5)
    38.5 (22.4 to 57.5)
    Attachments
    		 Relapse
    No statistical analyses for this end point

    Secondary: Time to best Single lineage response neutrophils

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    End point title
    		 Time to best Single lineage response neutrophils
    End point description
    The median time to best trilineage response for patients with response in the FAS population was 8.31 months. The median time to reach single lineage response was 7.08 months (erythroid), 5.52 months (platelet) and 2.91 months (neutrophil). A significant difference between the Placebo and Eltrombopag Arm was observed only for neutrophil response (p=0.025),
    End point type
    Secondary
    End point timeframe
    not special time point, will be measured in this analysis
    End point values
    		 Verum Placebo
    Number of subjects analysed
    32
    34
    Units: months
        arithmetic mean (standard deviation)
    4.13 ( 3.62 )
    6.51 ( 4.74 )
    Attachments
    		 Secondary endpoint Time to best neutrophil respons
    No statistical analyses for this end point

    Secondary: Time to best hematological response

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    End point title
    		 Time to best hematological response
    End point description
    The median time to best trilineage response for patients with response in the FAS population was 8.31 months. The median time to reach single lineage response was 7.08 months (erythroid), 5.52 months (platelet) and 2.91 months (neutrophil). A significant difference between the Placebo and Eltrombopag Arm was observed only for neutrophil response (p=0.025), see Table
    End point type
    Secondary
    End point timeframe
    depends on results, time of best response
    End point values
    		 Verum Placebo
    Number of subjects analysed
    30
    31
    Units: month
        arithmetic mean (standard deviation)
    9.35 ( 8.21 )
    10.26 ( 6.88 )
    Attachments
    		 Secondary endpoint Time to best response
    No statistical analyses for this end point

    Secondary: Time to best Single lineage response erythrocytes

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    End point title
    		 Time to best Single lineage response erythrocytes
    End point description
    The median time to best trilineage response for patients with response in the FAS population was 8.31 months. The median time to reach single lineage response was 7.08 months (erythroid), 5.52 months (platelet) and 2.91 months (neutrophil). A significant difference between the Placebo and Eltrombopag Arm was observed only for neutrophil response (p=0.025),
    End point type
    Secondary
    End point timeframe
    depending on result
    End point values
    		 Verum Placebo
    Number of subjects analysed
    26
    32
    Units: months
        arithmetic mean (standard deviation)
    8.47 ( 7.99 )
    8.58 ( 7.39 )
    Attachments
    		 Untitled (Filename: Secondary endpoint Time to best response.pdf)
    No statistical analyses for this end point

    Secondary: Time to best Single lineage response platelets

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    End point title
    		 Time to best Single lineage response platelets
    End point description
    Time to best Single lineage response platelets. The median time to best trilineage response for patients with response in the FAS population was 8.31 months. The median time to reach single lineage response was 7.08 months (erythroid), 5.52 months (platelet) and 2.91 months (neutrophil). A significant difference between the Placebo and Eltrombopag Arm was observed only for neutrophil response (p=0.025),
    End point type
    Secondary
    End point timeframe
    depend on results
    End point values
    		 Verum Placebo
    Number of subjects analysed
    28
    33
    Units: month
        arithmetic mean (standard deviation)
    5.32 ( 4.29 )
    6.89 ( 4.17 )
    Attachments
    		 Secondary endpoint Single lineage response erythro
    No statistical analyses for this end point

    Secondary: Number of pc units transfused within the first 6 months

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    End point title
    		 Number of pc units transfused within the first 6 months
    End point description
    There was no significant difference between the treatment arms in the proportion of patients requiring transfusions (Table 14.2.6.1) and in the number of transfused units. In the FAS population, a median number of 6 units of PC and 7 units of pRBC were transfused within the first 6 months,
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Verum Placebo
    Number of subjects analysed
    25
    20
    Units: PC
        arithmetic mean (standard deviation)
    9.2 ( 11.0 )
    14.0 ( 12.6 )
    Attachments
    		 transfusions at 6 months
    No statistical analyses for this end point

    Secondary: Number of pRBC units transfused within the first 6 months Status: Ready for collecting values

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    End point title
    		 Number of pRBC units transfused within the first 6 months Status: Ready for collecting values
    End point description
    There was no significant difference between the treatment arms in the proportion of patients requiring transfusions (Table 14.2.6.1) and in the number of transfused units (Table 14.2.6.2). In the FAS population, a median number of 6 units of PC and 7 units of pRBC were transfused within the first 6 months,
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 Verum Placebo
    Number of subjects analysed
    26
    27
    Units: pRBC
        arithmetic mean (standard deviation)
    8.5 ( 8.6 )
    10.2 ( 6.9 )
    Attachments
    		 Transfusion pRBC at 6 months
    No statistical analyses for this end point

    Secondary: FFS by study group

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    End point title
    		 FFS by study group
    End point description
    No significant difference was found between treatment arms (p=0.872). The median FFS was 24.86 weeks (95% CI 24.00; 87.29) in the Eltrombopag Arm and 24.29 weeks (95% CI 24.00; 36.00) in the Placebo Arm. The median FFS was longest in Group C with 99.00 weeks
    End point type
    Secondary
    End point timeframe
    dependend on result bei group B and C no upper value is available, therefore the results could not be entered without error warning. The available results are:Group Median (weeks) 95% CI B 36.00 [36.00; NA] C 99.00 [36.14; NA]
    End point values
    		 A: Placebo, no CR Arm D: Eltrombopag and non response (NR)
    Number of subjects analysed
    38
    9
    Units: weeks
        median (confidence interval 95%)
    24.50 (24.00 to 56.14)
    24.00 (24.00 to 24.00)
    Attachments
    		 Secondary endpoint FFS
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    between the first study-related procedure (i.e. screening) and 30 days post the last study treatment
    Adverse event reporting additional description
    All adverse events that occur between the first study-related procedure (i.e. screening) and 30 days post the last study treatment (or after this date if the investigator feels the event is related to the IMP) must be recorded. All Adverse Events will be graded according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE), available
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    28.0
    Reporting groups
    Reporting group title
    Verum (Eltrombopag) (TEAEs within 10 wks after therapy start)
    Reporting group description
    		 TEAEs in patients with Eltrombopag added to the background therapy (CSA) within 10 weeks after therapy start.

    Reporting group title
    Placebo (TEAEs reported within 10 weeks after therapy start)
    Reporting group description
    		 Overall summary of number of patients with TEAEs reported within 10 weeks after therapy start (SAF) treated with background therapy (CSA) + Placebo

    Reporting group title
    TEAEs reported after 6 months after therapy start
    Reporting group description
    		 TEAEs reported after 6 months after therapy start. Die Gesamtzahl der von schwerwiegenden unerwünschten Ereignissen betroffenen Probanden ist geringer als die Gesamtzahl der von schwerwiegenden unerwünschten Ereignissen betroffenen Probanden in der Berichtsgruppe. Berücksichtigen Sie alle betroffenen Probanden oder korrigieren Sie die Gesamtzahl der von schwerwiegenden unerwünschten Ereignissen betroffenen Probanden in der Berichtsgruppe.

    Reporting group title
    Verum (Eltrombopag) (TEAEs 10 wks -6 months)
    Reporting group description
    		 Verum (Eltrombopag) (TEAEs between 10 wks and 6 months after therapy start)

    Reporting group title
    Placebo (Eltrombopag) (TEAEs between 10 wks and 6 mo )
    Reporting group description
    		 Placebo (TEAEs between 10 wks and 6 months after therapy start)

    Serious adverse events
    		 Verum (Eltrombopag) (TEAEs within 10 wks after therapy start) Placebo (TEAEs reported within 10 weeks after therapy start) TEAEs reported after 6 months after therapy start Verum (Eltrombopag) (TEAEs 10 wks -6 months) Placebo (Eltrombopag) (TEAEs between 10 wks and 6 mo )
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 36 (8.33%)
    5 / 41 (12.20%)
    17 / 77 (22.08%)
    4 / 36 (11.11%)
    4 / 41 (9.76%)
         number of deaths (all causes)
    0
    1
    2
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 36 (2.78%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 41 (2.44%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Condition aggravated
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    1 / 36 (2.78%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Serum sickness
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Heavy menstrual bleeding
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    2 / 77 (2.60%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 41 (2.44%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Subcutaneous haematoma
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    1 / 36 (2.78%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 41 (2.44%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral venous thrombosis
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
    Additional description: Headache,
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 36 (2.78%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemolysis
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    1 / 36 (2.78%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Visual impairment
         subjects affected / exposed
    1 / 36 (2.78%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 36 (2.78%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 41 (2.44%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 41 (2.44%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 41 (2.44%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    1 / 36 (2.78%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubo-ovarian abscess
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 36 (0.00%)
    1 / 41 (2.44%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Verum (Eltrombopag) (TEAEs within 10 wks after therapy start) Placebo (TEAEs reported within 10 weeks after therapy start) TEAEs reported after 6 months after therapy start Verum (Eltrombopag) (TEAEs 10 wks -6 months) Placebo (Eltrombopag) (TEAEs between 10 wks and 6 mo )
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 36 (86.11%)
    39 / 41 (95.12%)
    58 / 77 (75.32%)
    30 / 36 (83.33%)
    28 / 41 (68.29%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    5 / 36 (13.89%)
    6 / 41 (14.63%)
    2 / 77 (2.60%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    5
    6
    3
    0
    0
    Hypertension
         subjects affected / exposed
    4 / 36 (11.11%)
    3 / 41 (7.32%)
    3 / 77 (3.90%)
    3 / 36 (8.33%)
    2 / 41 (4.88%)
         occurrences all number
    4
    3
    3
    3
    2
    General disorders and administration site conditions
    Nausea
         subjects affected / exposed
    6 / 36 (16.67%)
    9 / 41 (21.95%)
    4 / 77 (5.19%)
    4 / 36 (11.11%)
    2 / 41 (4.88%)
         occurrences all number
    6
    9
    8
    4
    2
    Fatigue
         subjects affected / exposed
    8 / 36 (22.22%)
    11 / 41 (26.83%)
    9 / 77 (11.69%)
    2 / 36 (5.56%)
    2 / 41 (4.88%)
         occurrences all number
    8
    11
    9
    2
    2
    Oedema peripheral
         subjects affected / exposed
    3 / 36 (8.33%)
    6 / 41 (14.63%)
    4 / 77 (5.19%)
    1 / 36 (2.78%)
    0 / 41 (0.00%)
         occurrences all number
    3
    6
    1
    1
    0
    Pyrexia
         subjects affected / exposed
    4 / 36 (11.11%)
    0 / 41 (0.00%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    4
    0
    1
    0
    0
    Reproductive system and breast disorders
    Dyspnoea
         subjects affected / exposed
    5 / 36 (13.89%)
    8 / 41 (19.51%)
    5 / 77 (6.49%)
    2 / 36 (5.56%)
    1 / 41 (2.44%)
         occurrences all number
    5
    8
    5
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    5 / 36 (13.89%)
    8 / 41 (19.51%)
    5 / 77 (6.49%)
    2 / 36 (5.56%)
    1 / 41 (2.44%)
         occurrences all number
    5
    8
    5
    2
    1
    Oropharyngeal pain
         subjects affected / exposed
    3 / 36 (8.33%)
    1 / 41 (2.44%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    3
    1
    1
    0
    0
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    2 / 36 (5.56%)
    3 / 41 (7.32%)
    2 / 77 (2.60%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    2
    3
    2
    0
    0
    Product issues
    Headache
         subjects affected / exposed
    10 / 36 (27.78%)
    15 / 41 (36.59%)
    8 / 77 (10.39%)
    6 / 36 (16.67%)
    3 / 41 (7.32%)
         occurrences all number
    14
    17
    10
    7
    3
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    2 / 36 (5.56%)
    3 / 41 (7.32%)
    3 / 77 (3.90%)
    2 / 36 (5.56%)
    1 / 41 (2.44%)
         occurrences all number
    2
    3
    3
    2
    1
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    8 / 36 (22.22%)
    6 / 41 (14.63%)
    5 / 77 (6.49%)
    1 / 36 (2.78%)
    1 / 41 (2.44%)
         occurrences all number
    8
    6
    5
    1
    1
    Dysaesthesia
         subjects affected / exposed
    1 / 36 (2.78%)
    5 / 41 (12.20%)
    0 / 77 (0.00%)
    1 / 36 (2.78%)
    1 / 41 (2.44%)
         occurrences all number
    1
    5
    0
    1
    1
    Dizziness
         subjects affected / exposed
    2 / 36 (5.56%)
    3 / 41 (7.32%)
    3 / 77 (3.90%)
    1 / 36 (2.78%)
    0 / 41 (0.00%)
         occurrences all number
    2
    3
    3
    1
    0
    Tremor
         subjects affected / exposed
    2 / 36 (5.56%)
    2 / 41 (4.88%)
    0 / 77 (0.00%)
    3 / 36 (8.33%)
    1 / 41 (2.44%)
         occurrences all number
    2
    2
    0
    3
    1
    Blood and lymphatic system disorders
    Petechia
         subjects affected / exposed
    4 / 36 (11.11%)
    0 / 41 (0.00%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 36 (2.78%)
    3 / 41 (7.32%)
    2 / 77 (2.60%)
    0 / 36 (0.00%)
    1 / 41 (2.44%)
         occurrences all number
    1
    3
    2
    0
    1
    Eye disorders
    Ocular icterus
         subjects affected / exposed
    7 / 36 (19.44%)
    1 / 41 (2.44%)
    0 / 77 (0.00%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    7
    1
    0
    0
    0
    Gastrointestinal disorders
    Gingival hypertrophy
         subjects affected / exposed
    7 / 36 (19.44%)
    9 / 41 (21.95%)
    4 / 77 (5.19%)
    6 / 36 (16.67%)
    3 / 41 (7.32%)
         occurrences all number
    7
    10
    4
    6
    3
    Abdominal pain
    Additional description: Abdominal pain and Abdominal pain upper
         subjects affected / exposed
    10 / 36 (27.78%)
    10 / 41 (24.39%)
    5 / 77 (6.49%)
    1 / 36 (2.78%)
    1 / 41 (2.44%)
         occurrences all number
    12
    10
    7
    1
    1
    Gingival bleeding
         subjects affected / exposed
    3 / 36 (8.33%)
    3 / 41 (7.32%)
    1 / 77 (1.30%)
    1 / 36 (2.78%)
    2 / 41 (4.88%)
         occurrences all number
    4
    3
    1
    1
    2
    Vomiting
    Additional description: Vomiting
         subjects affected / exposed
    2 / 36 (5.56%)
    2 / 41 (4.88%)
    2 / 77 (2.60%)
    1 / 36 (2.78%)
    2 / 41 (4.88%)
         occurrences all number
    2
    2
    2
    1
    2
    Abdominal pain upper
         subjects affected / exposed
    3 / 36 (8.33%)
    5 / 41 (12.20%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    2 / 41 (4.88%)
         occurrences all number
    5
    5
    2
    0
    2
    Hepatobiliary disorders
    Diarrhoea
         subjects affected / exposed
    3 / 36 (8.33%)
    3 / 41 (7.32%)
    4 / 77 (5.19%)
    1 / 36 (2.78%)
    2 / 41 (4.88%)
         occurrences all number
    3
    3
    4
    1
    2
    Skin and subcutaneous tissue disorders
    Hair growth abnormal
    Additional description: Hair growth abnormal including Hirsutism and Hypertrichiosis
         subjects affected / exposed
    3 / 36 (8.33%)
    7 / 41 (17.07%)
    3 / 77 (3.90%)
    8 / 36 (22.22%)
    10 / 41 (24.39%)
         occurrences all number
    3
    7
    3
    8
    10
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    9 / 36 (25.00%)
    14 / 41 (34.15%)
    7 / 77 (9.09%)
    3 / 36 (8.33%)
    2 / 41 (4.88%)
         occurrences all number
    9
    12
    5
    3
    2
    Arthralgia
         subjects affected / exposed
    1 / 36 (2.78%)
    3 / 41 (7.32%)
    1 / 77 (1.30%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    3
    0
    0
    0
    Back pain
         subjects affected / exposed
    1 / 36 (2.78%)
    2 / 41 (4.88%)
    4 / 77 (5.19%)
    0 / 36 (0.00%)
    0 / 41 (0.00%)
         occurrences all number
    1
    2
    5
    0
    0
    Infections and infestations
    Rhinitis
         subjects affected / exposed
    2 / 36 (5.56%)
    4 / 41 (9.76%)
    1 / 77 (1.30%)
    1 / 36 (2.78%)
    1 / 41 (2.44%)
         occurrences all number
    2
    4
    1
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 36 (5.56%)
    3 / 41 (7.32%)
    15 / 77 (19.48%)
    2 / 36 (5.56%)
    2 / 41 (4.88%)
         occurrences all number
    2
    3
    12
    2
    3
    Nasopharingitis
         subjects affected / exposed
    1 / 36 (2.78%)
    1 / 41 (2.44%)
    2 / 77 (2.60%)
    2 / 36 (5.56%)
    2 / 41 (4.88%)
         occurrences all number
    1
    1
    2
    2
    3
    COVID-19
    Additional description: including Coronavirus infection
         subjects affected / exposed
    0 / 36 (0.00%)
    0 / 41 (0.00%)
    10 / 77 (12.99%)
    2 / 36 (5.56%)
    0 / 41 (0.00%)
         occurrences all number
    0
    0
    10
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 May 2017
    Substantial protocol changes The study was conducted according to the Clinical Study Protocol (CSP) version 1.15 dated 08 Jan 2015 and the following amendments: • Version 2.0 dated 08 May 2017: change of financial support and marketing authorization holder of Investigational Medicinal Product (IMP)
    31 May 2017
    Substantial protocol changes The study was conducted according to the Clinical Study Protocol (CSP) version 1.15 dated 08 Jan 2015 and the following amendments: • Version 3.0 dated 31 May 2017: corrections of terms and clarifications approved by the ethics committee
    03 Mar 2020
    Substantial protocol changes The study was conducted according to the Clinical Study Protocol (CSP) version 1.15 dated 08 Jan 2015 and the following amendments: • Version 4.0 dated 03 Mar 2020: reduction of sample size and follow-up period, modification of the pharmacokinetic section, adjustment of eltrombopag treatment period
    22 Jul 2021
    Substantial protocol changes The study was conducted according to the Clinical Study Protocol (CSP) version 1.15 dated 08 Jan 2015 and the following amendments: • Version 4.1 dated 22 Jul 2021: initial protocol for France
    28 Apr 2022
    Substantial protocol changes The study was conducted according to the Clinical Study Protocol (CSP) version 1.15 dated 08 Jan 2015 and the following amendments: • Version 5.0 dated 28 Apr 2022: extension of recruitment period and adjustment of study timelines, addition of telomeric analysis and flow cytometry for Group A2 visit XIII
    09 Oct 2024
    Version 6.0 dated 09 Oct 2024: administrative changes at the Sponsor, addition of an exploratory endpoint, change of the end of trial definition

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

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