Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase III double-blind, randomized, parallel group, multicenter placebo-controlled trial to study the efficacy and safety of caplacizumab in patients with acquired thrombotic thrombocytopenic purpura.

    Summary
    EudraCT number
    		 2015-001098-42
    Trial protocol
    		 BE   CZ   ES   AT   DE   HU   NL   Outside EU/EEA   IT  
    Global end of trial date
    16 Aug 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Aug 2018
    First version publication date
    20 Jul 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALX0681-C301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02553317
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ablynx
    Sponsor organisation address
    Technologiepark 21, Zwijnaarde, Belgium, 9052
    Public contact
    Medical Monitor, Ablynx, 32 (0)9 262 00 00 , clinicaltrials@ablynx.com
    Scientific contact
    Medical Monitor, Ablynx, 32 (0)9 262 00 00 , clinicaltrials@ablynx.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001157-PIP01-11
    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
    20 Sep 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Aug 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Aug 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate efficacy of caplacizumab in more rapidly restoring normal platelet counts as measure of prevention of further microvascular thrombosis.
    Protection of trial subjects
    Only subjects who met all the study inclusion criteria and none of the exclusion criteria were to be randomized to study treatment. All subjects were free to withdraw from the clinical study at any time for any reason. Close monitoring of all subjects was to be adhered to throughout the study.
    Background therapy
    		 - Plasma exchange (PE) with plasma (e.g., fresh frozen plasma, solvent detergent/viral-inactivated plasma, cryosupernatant) at 1 to 1.5x estimated plasma volume daily. Once the platelet count was ≥ 150,000/µL, daily PE had to continue for at least 2 days. Tapering of PE after platelet count normalization, defined as reducing its frequency to less than once per day, was strongly discouraged and, if considered, had to be discussed with the Medical Monitor. - Corticosteroid treatment was to be given at a dose of at least 1 mg/kg/day during daily PE and continued for the first week after the end of daily PE. Afterwards, corticosteroids could be tapered at the discretion of the Investigator, with the aim of being corticosteroid-free by Day 30 after stop of daily PE as clinically indicated. Other immunosuppressive treatment (e.g. rituximab) was permitted, per standard site practice.
    Evidence for comparator
    		 not applicable
    Actual start date of recruitment
    19 Nov 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
    Netherlands: 1
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    United Kingdom: 21
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    Belgium: 8
    Country: Number of subjects enrolled
    Czech Republic: 4
    Country: Number of subjects enrolled
    France: 12
    Country: Number of subjects enrolled
    Hungary: 7
    Country: Number of subjects enrolled
    Canada: 13
    Country: Number of subjects enrolled
    Turkey: 9
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    United States: 32
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    Italy: 10
    Worldwide total number of subjects
    145
    EEA total number of subjects
    81
    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)
    133
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 145 subjects was randomized at 55 sites located in Europe (34 sites; 91 subjects), Asia (4 sites, 6 subjects), Australia (3 sites, 3 subjects), and North America (14 sites; 45 subjects). Consent was obtained from the first subject on 19 Nov 2015; the last subject completed the final visit on 16 Aug 2017.

    Pre-assignment
    Screening details
    		 Of the 149 subjects screened, 4 were screen failures and 145 were randomly assigned to treatment (Intent-to-treat [ITT] population). All, except for 1 subject, received study drug and were included in the safety population and in the modified ITT (mITT) population.

    Period 1
    Period 1 title
    Overall Study Period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor
    Blinding implementation details
    Study drug treatment allocation was double-blind (DB). In case of a recurrence (i.e., defined as recurrent thrombocytopenia after initial recovery of platelet count requiring re-initiation of daily PE, occurring during the post-daily PE treatment period), subjects received open-label (OL) caplacizumab together with daily PE, irrespective of the initial treatment allocation. The blind for the initial treatment allocation was not broken.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Caplacizumab
    Arm description
    		 Caplacizumab 10 mg once daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Caplacizumab
    Investigational medicinal product code
    ALX-0081
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    - First day of treatment: 10 mg intravenous injection prior to plasma exchange followed by a 10 mg subcutaneous injection (in the abdominal region) after completion of plasma exchange on that day. - Subsequent days of treatment during plasma exchange: daily 10 mg subcutaneous injection (in the abdominal region) following plasma exchange - Treatment after plasma exchange period: daily 10 mg subcutaneous injections for 30 days. If the underlying immunological disease was not resolved, treatment could be extended for a maximum of 4 additional 1-week periods (i.e., 28 days) and was to be accompanied by optimization of immunosuppression.

    Arm title
    		 Placebo
    Arm description
    		 Placebo once daily
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Intravenous use, Subcutaneous use
    Dosage and administration details
    - First day of treatment: intravenous injection prior to plasma exchange followed by a subcutaneous injection after completion of plasma exchange on that day. - Subsequent days of treatment during plasma exchange: daily subcutaneous injection following plasma exchange - Treatment after plasma exchange period: daily subcutaneous injections for 30 days. If the underlying immunological disease was not resolved, treatment could be extended for a maximum of 4 additional 1-week periods (i.e., 28 days) and was to be accompanied by optimization of immunosuppression.

    Number of subjects in period 1
    		Caplacizumab Placebo
    Started
    72
    73
    Completed
    58
    50
    Not completed
    14
    23
         Adverse event, serious fatal
    1
    3
         Consent withdrawn by subject
    4
    5
         Physician decision
    2
    4
         Adverse event, non-fatal
    6
    5
         Consent withdrawn by legal representative
    -
    1
         Other
    1
    3
         Non-compliance with study drug
    -
    1
         Lost to follow-up
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Caplacizumab
    Reporting group description
    		 Caplacizumab 10 mg once daily

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo once daily

    Reporting group values
    		 Caplacizumab Placebo Total
    Number of subjects
    		 72 73 145
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 68 65 133
        From 65-84 years
    		 4 8 12
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 44.9 ( 13.46 ) 47.3 ( 14.07 ) -
    Gender categorical
    Units: Subjects
        Female
    		 49 51 100
        Male
    		 23 22 45

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Caplacizumab
    Reporting group description
    		 Caplacizumab 10 mg once daily

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo once daily

    Primary: Time to platelet count response

    		 Close Top of page
    End point title
    		 Time to platelet count response
    End point description
    Platelet count response was defined as initial platelet count ≥ 150,000/µL with subsequent stop of daily PE within 5 days. It refers to the first time both conditions, platelet count ≥ 150,000/µL and the stop of daily PE within 5 days, were met. There was a statistically significant reduction in time to confirmed platelet response in the DB caplacizumab group, compared to the DB placebo group based on the Kaplan-Meier (KM) analysis and a stratified log-rank test (p = 0.0099). This was confirmed by a hazard, or platelet count normalization rate, ratio (95% CI) for the DB caplacizumab group versus the DB placebo group of 1.55 (1.095; 2.195) based on a Cox proportional hazards model. This means that at any given time point, subjects treated with caplacizumab were 1.55 times more likely to achieve platelet count response compared to subjects treated with placebo.
    End point type
    Primary
    End point timeframe
    Only data from the double blind daily PE period up to the cut-off point were used. The cut-off point was defined by, whichever occurred first: - 45 days of daily PE after the start of study drug - the stop of daily PE - the stop of study drug treatment
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [1]
    73 [2]
    Units: day
        median (confidence interval 95%)
    2.69 (1.89 to 2.83)
    2.88 (2.68 to 3.56)
    Attachments
    		 Time to platelet count response figures
    Notes
    [1] - Intent-to-treat population (for the respective study period)
    [2] - Intent-to-treat population (for the respective study period)
    Statistical analysis title
    		 stratified log-rank test
    Statistical analysis description
    Time to platelet count response in the caplacizumab arm and placebo arm was compared by conducting a two-sided stratified log-rank test based on a KM analysis, with severity of neurological involvement (according to the Glasgow coma scale [GCS] category, stratification factor used in randomization: ≤12 / 13-15) as stratification factor. The resulting p-value was compared with a significance level of 5%.
    Comparison groups
    Caplacizumab v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0099
    Method
    		 Logrank
    Confidence interval
    Statistical analysis title
    		 Cox proportional hazard model
    Statistical analysis description
    Time to platelet count response was analyzed using a Cox proportional hazards regression model with time to platelet count response as dependent variable, and treatment group and GCS category as independent variables. The hazard (or platelet count normalization rate) ratio from the Cox model was reported along with 95% CI.
    Comparison groups
    Caplacizumab v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.095
         upper limit
    		 2.195

    Secondary: Proportion of subjects with TTP-Related Death, Recurrence of TTP, or a Major Thromboembolic Event During the Study Drug Treatment Period

    		 Close Top of page
    End point title
    		 Proportion of subjects with TTP-Related Death, Recurrence of TTP, or a Major Thromboembolic Event During the Study Drug Treatment Period
    End point description
    The proportion of subjects with TTP-related death, a recurrence of TTP, or at least one treatment-emergent major thromboembolic event in the ITT population (i.e., the first key secondary endpoint).
    End point type
    Secondary
    End point timeframe
    The study drug treatment period. For both treatment groups, only events that occurred prior to a switch to open-label caplacizumab were evaluated for this analysis.
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [3]
    73 [4]
    Units: percent
    13
    49
    Notes
    [3] - Intent-to-treat population (for the respective study period)
    [4] - Intent-to-treat population (for the respective study period)
    Statistical analysis title
    		 Cochran-Mantel-Haenszel (CMH) test
    Statistical analysis description
    A Cochran-Mantel-Haenszel (CMH) test was conducted with adjustment for GCS category (stratification factor used in randomization).
    Comparison groups
    Caplacizumab v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Proportion of subjects with a recurrence of TTP in the Overall Study Period

    		 Close Top of page
    End point title
    		 Proportion of subjects with a recurrence of TTP in the Overall Study Period
    End point description
    The proportion of subjects with a recurrence of TTP during the overall study period (i.e., including follow-up [FU]) (i.e., the second key secondary endpoint).
    End point type
    Secondary
    End point timeframe
    The overall study period (covers both the overall treatment period and the follow-up period)
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [5]
    73 [6]
    Units: percent
    13
    38
    Notes
    [5] - Intent-to-treat population (for the respective study period)
    [6] - Intent-to-treat population (for the respective study period)
    Statistical analysis title
    		 Cochran-Mantel-Haenszel (CMH) test
    Statistical analysis description
    A CMH test was conducted with adjustment for GCS category (stratification factor used in randomization).
    Comparison groups
    Caplacizumab v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0004
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: The proportion of subjects with refractory disease

    		 Close Top of page
    End point title
    		 The proportion of subjects with refractory disease
    End point description
    Proportion of subjects with refractory TTP, defined as absence of platelet count doubling after 4 days of standard treatment, and lactate dehydrogenase (LDH) > upper limit of normal (ULN) (i.e., the third key secondary endpoint).
    End point type
    Secondary
    End point timeframe
    The study drug treatment period
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [7]
    73 [8]
    Units: percent
    0
    4
    Notes
    [7] - Intent-to-treat population (for the respective study period)
    [8] - Intent-to-treat population (for the respective study period)
    Statistical analysis title
    		 Cochran-Mantel-Haenszel (CMH) test
    Statistical analysis description
    A CMH test was conducted with adjustment for GCS category (stratification factor used in randomization).
    Comparison groups
    Caplacizumab v Placebo
    Number of subjects included in analysis
    144
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0572
    Method
    		 Cochran-Mantel-Haenszel
    Confidence interval

    Secondary: Time to normalization of organ damage marker levels

    		 Close Top of page
    End point title
    		 Time to normalization of organ damage marker levels
    End point description
    Time to first normalization of LDH, cardiac troponin I (cTnI) and serum creatinine was defined as: first time of LDH ≤ ULN and cTnI ≤ ULN and serum creatinine ≤ ULN - time of first i.v. loading dose of study drug after randomization + 1 minute. Subjects in either initial treatment group who switched to open-label caplacizumab before having reached the endpoint were censored at time of switch. Of note, the key secondary endpoints were hierarchically ordered to allow statistical testing for these endpoints at the same nominal significance level of 5% without adjustment, as long as the tests occurred in the pre-defined sequential order, and given that all null hypotheses tested for endpoints with a higher rank (including the primary endpoint) were rejected. No confirmatory testing was done for this fourth key secondary endpoint, as the statistical test was not significant for the proportion of subjects with refractory disease (i.e., the third key secondary endpoint).
    End point type
    Secondary
    End point timeframe
    Overall study period (excluding the open-label period)
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    65 [9]
    66 [10]
    Units: day
        median (confidence interval 95%)
    2.86 (1.93 to 3.86)
    3.36 (1.88 to 7.71)
    Notes
    [9] - Intent-to-treat population (for the respective study period) with biomarker level data available
    [10] - Intent-to-treat population (for the respective study period) with biomarker level data available
    No statistical analyses for this end point

    Other pre-specified: Number of days of plasma exchange

    		 Close Top of page
    End point title
    		 Number of days of plasma exchange
    End point description
    The number of days of plasma exchange (PE) during the overall study drug treatment period, including the number of days of PE during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).
    End point type
    Other pre-specified
    End point timeframe
    Overall study drug treatment period
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [11]
    73 [12]
    Units: day
        arithmetic mean (standard error)
    5.8 ( 0.51 )
    9.4 ( 0.81 )
    Notes
    [11] - Intent-to-treat population (for the respective study period)
    [12] - Intent-to-treat population (for the respective study period)
    No statistical analyses for this end point

    Other pre-specified: Total volume of plasma exchange

    		 Close Top of page
    End point title
    		 Total volume of plasma exchange
    End point description
    The total volume of plasma exchange (PE) during the overall study drug treatment Period, including the total volume of PE during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).
    End point type
    Other pre-specified
    End point timeframe
    Overall study drug treatment period
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [13]
    73 [14]
    Units: litre(s)
        arithmetic mean (standard error)
    21.33 ( 1.619 )
    35.93 ( 4.169 )
    Notes
    [13] - Intent-to-treat population (for the respective study period)
    [14] - Intent-to-treat population (for the respective study period)
    No statistical analyses for this end point

    Other pre-specified: Number of days in intensive care unit

    		 Close Top of page
    End point title
    		 Number of days in intensive care unit
    End point description
    The number of days in intensive care unit (ICU) during the overall study drug treatment period, including the number of days in ICU during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).
    End point type
    Other pre-specified
    End point timeframe
    Overall study drug treatment period
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [15]
    73 [16]
    Units: day
        arithmetic mean (standard error)
    3.4 ( 0.40 )
    9.7 ( 2.12 )
    Notes
    [15] - Intent-to-treat population (for the respective study period)
    [16] - Intent-to-treat population (for the respective study period)
    No statistical analyses for this end point

    Other pre-specified: Number of days in hospital

    		 Close Top of page
    End point title
    		 Number of days in hospital
    End point description
    The number of days in hospital during the overall study drug treatment period, including the number of days in hospital during the open-label study drug treatment period. Data were analyzed according to the initial treatment allocation (both before and after switch to open-label caplacizumab).
    End point type
    Other pre-specified
    End point timeframe
    Overall study drug treatment period
    End point values
    		 Caplacizumab Placebo
    Number of subjects analysed
    71 [17]
    73 [18]
    Units: day
        arithmetic mean (standard error)
    9.9 ( 0.70 )
    14.4 ( 1.22 )
    Notes
    [17] - Intent-to-treat population (for the respective study period)
    [18] - Intent-to-treat population (for the respective study period)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From time of first study drug administration until the subject's study completion/discontinuation date.
    Adverse event reporting additional description
    Double Blind Caplacizumab/Double Blind placebo groups (subjects randomized to capacizumab/placebo, respectively): AEs starting in the DB or FU Periods for subjects with no OL Period. Only AEs starting in the DB Period for subjects with an OL Period OL Caplacizumab group (all subjects with OL Period): AEs starting in the OL or FU Periods
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Double-blind Caplacizumab
    Reporting group description
    		 Caplacizumab 10 mg once daily

    Reporting group title
    Double-blind Placebo
    Reporting group description
    		 Placebo once daily

    Reporting group title
    Open-label Caplacizumab
    Reporting group description
    		 In case of recurrence: open-label caplacizumab 10 mg once daily

    Serious adverse events
    		 Double-blind Caplacizumab Double-blind Placebo Open-label Caplacizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    28 / 71 (39.44%)
    39 / 73 (53.42%)
    7 / 28 (25.00%)
         number of deaths (all causes)
    1
    3
    0
         number of deaths resulting from adverse events
    1
    3
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Serum sickness
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic ovarian cyst
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    4 / 71 (5.63%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
    Additional description: Verbatim term of SAE with fatal outcome : Hypoxia with bleeding into the lung
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 73 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic transfusion reaction
         subjects affected / exposed
    0 / 71 (0.00%)
    3 / 73 (4.11%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriospasm coronary
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac tamponade
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
    Additional description: verbatim term of SAE with fatal outcome: cerebral ischemia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhagic transformation stroke
    Additional description: Verbatim term of SAE with fatal outcome: worsened massive ischemic stroke with hemorrhagic transformation
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 73 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombotic thrombocytopenic purpura
    Additional description: Verbatim term of SAE with fatal outcome: worsening thrombotic thrombocytopenic purpura (TTP) with coma and death
         subjects affected / exposed
    9 / 71 (12.68%)
    29 / 73 (39.73%)
    4 / 28 (14.29%)
         occurrences causally related to treatment / all
    0 / 9
    2 / 29
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gingival bleeding
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer haemorrhage
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal necrosis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal perforation
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder necrosis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash erythematous
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 73 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthropathy
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Septic shock
    Additional description: verbatim term of SAE with fatal outcome: septic shock
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 73 (2.74%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Double-blind Caplacizumab Double-blind Placebo Open-label Caplacizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    67 / 71 (94.37%)
    65 / 73 (89.04%)
    25 / 28 (89.29%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    4 / 71 (5.63%)
    8 / 73 (10.96%)
    1 / 28 (3.57%)
         occurrences all number
    4
    8
    1
    Haematoma
         subjects affected / exposed
    3 / 71 (4.23%)
    2 / 73 (2.74%)
    2 / 28 (7.14%)
         occurrences all number
    7
    2
    2
    Hypotension
         subjects affected / exposed
    4 / 71 (5.63%)
    2 / 73 (2.74%)
    1 / 28 (3.57%)
         occurrences all number
    4
    3
    1
    Hot flush
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 73 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    General disorders and administration site conditions
    Catheter site haemorrhage
         subjects affected / exposed
    5 / 71 (7.04%)
    5 / 73 (6.85%)
    8 / 28 (28.57%)
         occurrences all number
    6
    5
    10
    Fatigue
         subjects affected / exposed
    10 / 71 (14.08%)
    6 / 73 (8.22%)
    2 / 28 (7.14%)
         occurrences all number
    10
    6
    2
    Pyrexia
         subjects affected / exposed
    10 / 71 (14.08%)
    6 / 73 (8.22%)
    1 / 28 (3.57%)
         occurrences all number
    12
    6
    1
    Oedema peripheral
         subjects affected / exposed
    4 / 71 (5.63%)
    7 / 73 (9.59%)
    1 / 28 (3.57%)
         occurrences all number
    4
    8
    2
    Asthenia
         subjects affected / exposed
    2 / 71 (2.82%)
    4 / 73 (5.48%)
    2 / 28 (7.14%)
         occurrences all number
    3
    4
    3
    Chest pain
         subjects affected / exposed
    1 / 71 (1.41%)
    5 / 73 (6.85%)
    1 / 28 (3.57%)
         occurrences all number
    1
    6
    1
    Catheter site pain
         subjects affected / exposed
    1 / 71 (1.41%)
    5 / 73 (6.85%)
    0 / 28 (0.00%)
         occurrences all number
    1
    5
    0
    Injection site pain
         subjects affected / exposed
    1 / 71 (1.41%)
    4 / 73 (5.48%)
    1 / 28 (3.57%)
         occurrences all number
    1
    4
    1
    Pain
         subjects affected / exposed
    4 / 71 (5.63%)
    1 / 73 (1.37%)
    0 / 28 (0.00%)
         occurrences all number
    7
    1
    0
    Injection site haematoma
         subjects affected / exposed
    1 / 71 (1.41%)
    3 / 73 (4.11%)
    2 / 28 (7.14%)
         occurrences all number
    1
    4
    2
    Injection site erythema
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 73 (1.37%)
    2 / 28 (7.14%)
         occurrences all number
    1
    1
    4
    Injection site pruritus
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 73 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    2
    0
    2
    Injection site reaction
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 73 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    1
    0
    2
    Face oedema
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 73 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Reproductive system and breast disorders
    Vaginal haemorrhage
         subjects affected / exposed
    4 / 71 (5.63%)
    2 / 73 (2.74%)
    1 / 28 (3.57%)
         occurrences all number
    5
    2
    1
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    21 / 71 (29.58%)
    2 / 73 (2.74%)
    5 / 28 (17.86%)
         occurrences all number
    32
    2
    5
    Dyspnoea
         subjects affected / exposed
    7 / 71 (9.86%)
    2 / 73 (2.74%)
    2 / 28 (7.14%)
         occurrences all number
    10
    2
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 71 (8.45%)
    8 / 73 (10.96%)
    0 / 28 (0.00%)
         occurrences all number
    7
    8
    0
    Anxiety
         subjects affected / exposed
    4 / 71 (5.63%)
    6 / 73 (8.22%)
    1 / 28 (3.57%)
         occurrences all number
    4
    6
    1
    Agitation
         subjects affected / exposed
    5 / 71 (7.04%)
    4 / 73 (5.48%)
    0 / 28 (0.00%)
         occurrences all number
    6
    4
    0
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 73 (1.37%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    2
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    5 / 71 (7.04%)
    10 / 73 (13.70%)
    2 / 28 (7.14%)
         occurrences all number
    7
    24
    10
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    4 / 71 (5.63%)
    3 / 73 (4.11%)
    1 / 28 (3.57%)
         occurrences all number
    4
    5
    4
    Tachycardia
         subjects affected / exposed
    2 / 71 (2.82%)
    4 / 73 (5.48%)
    1 / 28 (3.57%)
         occurrences all number
    2
    4
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    14 / 71 (19.72%)
    6 / 73 (8.22%)
    6 / 28 (21.43%)
         occurrences all number
    18
    10
    6
    Dizziness
         subjects affected / exposed
    7 / 71 (9.86%)
    8 / 73 (10.96%)
    2 / 28 (7.14%)
         occurrences all number
    8
    8
    3
    Paraesthesia
         subjects affected / exposed
    8 / 71 (11.27%)
    6 / 73 (8.22%)
    0 / 28 (0.00%)
         occurrences all number
    9
    6
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 71 (5.63%)
    6 / 73 (8.22%)
    4 / 28 (14.29%)
         occurrences all number
    4
    9
    8
    Eye disorders
    Vision blurred
         subjects affected / exposed
    5 / 71 (7.04%)
    5 / 73 (6.85%)
    0 / 28 (0.00%)
         occurrences all number
    6
    5
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    10 / 71 (14.08%)
    7 / 73 (9.59%)
    2 / 28 (7.14%)
         occurrences all number
    12
    8
    2
    Gingival bleeding
         subjects affected / exposed
    12 / 71 (16.90%)
    1 / 73 (1.37%)
    4 / 28 (14.29%)
         occurrences all number
    13
    1
    5
    Constipation
         subjects affected / exposed
    7 / 71 (9.86%)
    5 / 73 (6.85%)
    4 / 28 (14.29%)
         occurrences all number
    7
    6
    6
    Diarrhoea
         subjects affected / exposed
    7 / 71 (9.86%)
    5 / 73 (6.85%)
    4 / 28 (14.29%)
         occurrences all number
    7
    5
    7
    Abdominal pain
         subjects affected / exposed
    5 / 71 (7.04%)
    4 / 73 (5.48%)
    2 / 28 (7.14%)
         occurrences all number
    5
    4
    4
    Vomiting
         subjects affected / exposed
    3 / 71 (4.23%)
    4 / 73 (5.48%)
    2 / 28 (7.14%)
         occurrences all number
    3
    5
    2
    Abdominal pain upper
         subjects affected / exposed
    1 / 71 (1.41%)
    1 / 73 (1.37%)
    4 / 28 (14.29%)
         occurrences all number
    1
    1
    8
    Dyspepsia
         subjects affected / exposed
    2 / 71 (2.82%)
    1 / 73 (1.37%)
    2 / 28 (7.14%)
         occurrences all number
    2
    1
    2
    Haematochezia
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 73 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    5
    0
    2
    Lip haemorrhage
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 73 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    12 / 71 (16.90%)
    5 / 73 (6.85%)
    1 / 28 (3.57%)
         occurrences all number
    14
    8
    1
    Rash
         subjects affected / exposed
    5 / 71 (7.04%)
    9 / 73 (12.33%)
    4 / 28 (14.29%)
         occurrences all number
    6
    11
    4
    Pruritus
         subjects affected / exposed
    5 / 71 (7.04%)
    6 / 73 (8.22%)
    2 / 28 (7.14%)
         occurrences all number
    6
    6
    4
    Petechiae
         subjects affected / exposed
    4 / 71 (5.63%)
    5 / 73 (6.85%)
    3 / 28 (10.71%)
         occurrences all number
    4
    5
    5
    Ecchymosis
         subjects affected / exposed
    2 / 71 (2.82%)
    4 / 73 (5.48%)
    3 / 28 (10.71%)
         occurrences all number
    2
    4
    3
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    5 / 71 (7.04%)
    2 / 73 (2.74%)
    2 / 28 (7.14%)
         occurrences all number
    7
    2
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    4 / 71 (5.63%)
    6 / 73 (8.22%)
    0 / 28 (0.00%)
         occurrences all number
    5
    7
    0
    Arthralgia
         subjects affected / exposed
    4 / 71 (5.63%)
    3 / 73 (4.11%)
    3 / 28 (10.71%)
         occurrences all number
    4
    3
    4
    Back pain
         subjects affected / exposed
    5 / 71 (7.04%)
    3 / 73 (4.11%)
    1 / 28 (3.57%)
         occurrences all number
    5
    3
    1
    Muscular weakness
         subjects affected / exposed
    4 / 71 (5.63%)
    2 / 73 (2.74%)
    0 / 28 (0.00%)
         occurrences all number
    5
    2
    0
    Myalgia
         subjects affected / exposed
    2 / 71 (2.82%)
    1 / 73 (1.37%)
    2 / 28 (7.14%)
         occurrences all number
    2
    1
    3
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    4 / 71 (5.63%)
    4 / 73 (5.48%)
    0 / 28 (0.00%)
         occurrences all number
    4
    4
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    4 / 71 (5.63%)
    0 / 73 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    4
    0
    0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    6 / 71 (8.45%)
    14 / 73 (19.18%)
    2 / 28 (7.14%)
         occurrences all number
    6
    15
    2
    Hyperglycaemia
         subjects affected / exposed
    4 / 71 (5.63%)
    4 / 73 (5.48%)
    1 / 28 (3.57%)
         occurrences all number
    5
    4
    2
    Hypocalcaemia
         subjects affected / exposed
    1 / 71 (1.41%)
    5 / 73 (6.85%)
    2 / 28 (7.14%)
         occurrences all number
    1
    8
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Apr 2016
    The main reason for the first protocol amendment was rewording and reordering of key and other secondary endpoints in view of hierarchical statistical testing for the key secondary endpoints. In addition, the interim analysis of efficacy was removed and the description of analysis of key secondary endpoints was updated to reflect the hierarchical testing. The secondary objectives were reworded to correspond to the rewording of the secondary endpoints.
    20 Jul 2016
    The main reason for the second protocol amendment was to increase the planned sample size. The number of subjects planned to be included in the study was increased from 92 to 132 to account for a change in the assumed treatment difference for the primary endpoint in the sample size calculation, to account for drop-outs, and to increase the statistical power of the key secondary endpoint analyses.

    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
    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.

    European Medicines Agency © 1995-Sat Apr 27 19:02:33 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA