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    Clinical Trial Results:
    A Phase 3, Pivotal, Open-label, Multicenter Study to Assess the Efficacy and Safety of BIVV009 in Patients With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion

    Summary
    EudraCT number
    2017-003538-10
    Trial protocol
    AT   GB   DE   NO   ES   BE   NL   IT  
    Global end of trial date
    05 Oct 2021

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Oct 2022
    First version publication date
    20 Oct 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    BIVV009-03
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03347396
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Sanofi study ID: EFC16215, Study name: Cardinal, IND #: 128,190
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 avenue Pierre Brossolette, Chilly-Mazarin, France, 91380
    Public contact
    Trial Transparency Team, Bioverativ, a Sanofi company, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Bioverativ, a Sanofi company, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Oct 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Oct 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Part A: The primary objective of Part A was to determine whether BIVV009 administration results in a greater than or equal to (>=) 2 grams per decilitre (g/dL) increase in hemoglobin (Hgb) levels or increases Hgb to >=12 g/dL and obviates the need for blood transfusion during treatment in subjects with cold agglutinin disease (CAD) who had a recent history of blood transfusion. Part B: The primary objective of Part B was to evaluate the long-term safety and tolerability of BIVV009 in subjects with primary CAD.
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    05 Mar 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Norway: 3
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Japan: 3
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    24
    EEA total number of subjects
    15
    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)
    5
    From 65 to 84 years
    18
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 16 active sites in 8 countries. Out of 42 screened subjects, a total of 24 subjects were enrolled from 05 March 2018 to 10 Jan 2019. This was a single arm study, consisted of 2 Parts: Part A and Part B.

    Pre-assignment
    Screening details
    Subjects were stratified based on baseline body weight to receive BIVV009 6.5 grams (g) (if <75 kg) or 7.5 g (if >=75 kg). As planned, data presented as: 1) Dose-wise (2 dose cohorts: BIVV009 6.5 g & BIVV009 7.5 g) for sections, ‘disposition, baseline characteristics, safety endpoints & AEs’. 2) combined population (BIVV009) for efficacy endpoints.

    Period 1
    Period 1 title
    Part A (Week 26)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    BIVV009 6.5 g
    Arm description
    Subjects with primary CAD and body weight less than (<)75 kilograms (kg) with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an intravenous (IV) infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All subjects who completed Part A elected to continue in Part B.
    Arm type
    Experimental

    Investigational medicinal product name
    BIVV009
    Investigational medicinal product code
    Other name
    Sutimlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects with body weight <75 kg received fixed doses of BIVV009 6.5 g as IV infusion on Day 0 and Day 7 and every 14 days thereafter up to Week 25.

    Arm title
    BIVV009 7.5 g
    Arm description
    Subjects with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All subjects who completed Part A elected to continue in Part B.
    Arm type
    Experimental

    Investigational medicinal product name
    BIVV009
    Investigational medicinal product code
    Other name
    Sutimlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects with body weight >=75 kg received fixed doses of BIVV009 7.5 g as IV infusion on Day 0 and Day 7 and every 14 days thereafter up to Week 25.

    Number of subjects in period 1
    BIVV009 6.5 g BIVV009 7.5 g
    Started
    17
    7
    Completed
    16
    6
    Not completed
    1
    1
         Death
    -
    1
         Adverse event
    1
    -
    Period 2
    Period 2 title
    Part B (149 weeks)
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    BIVV009 6.5 g
    Arm description
    Subjects with primary CAD and body weight <75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All subjects who completed Part A elected to continue in Part B.
    Arm type
    Experimental

    Investigational medicinal product name
    BIVV009
    Investigational medicinal product code
    Other name
    Sutimlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects with body weight <75 kg received fixed doses of BIVV009 6.5 g as IV infusion every 2 weeks starting at Week 27 during Part B up to 143 weeks.

    Arm title
    BIVV009 7.5 g
    Arm description
    Subjects with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All subjects who completed Part A elected to continue in Part B.
    Arm type
    Experimental

    Investigational medicinal product name
    BIVV009
    Investigational medicinal product code
    Other name
    Sutimlimab
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Subjects with body weight >=75 kg received fixed doses of BIVV009 7.5 g as IV infusion every 2 weeks starting at Week 27 during Part B up to 149 weeks.

    Number of subjects in period 2
    BIVV009 6.5 g BIVV009 7.5 g
    Started
    16
    6
    Completed
    14
    5
    Not completed
    2
    1
         Death
    1
    -
         Adverse event
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    BIVV009 6.5 g
    Reporting group description
    Subjects with primary CAD and body weight less than (<)75 kilograms (kg) with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an intravenous (IV) infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All subjects who completed Part A elected to continue in Part B.

    Reporting group title
    BIVV009 7.5 g
    Reporting group description
    Subjects with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All subjects who completed Part A elected to continue in Part B.

    Reporting group values
    BIVV009 6.5 g BIVV009 7.5 g Total
    Number of subjects
    17 7 24
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    71.8 ± 9.05 70.1 ± 6.01 -
    Gender categorical
    Units: Subjects
        Female
    11 4 15
        Male
    6 3 9
    Race
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        Asian
    3 0 3
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Black or African American
    0 0 0
        White
    2 1 3
        More than one race
    0 0 0
        Unknown or Not Reported
    12 6 18

    End points

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    End points reporting groups
    Reporting group title
    BIVV009 6.5 g
    Reporting group description
    Subjects with primary CAD and body weight less than (<)75 kilograms (kg) with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an intravenous (IV) infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All subjects who completed Part A elected to continue in Part B.

    Reporting group title
    BIVV009 7.5 g
    Reporting group description
    Subjects with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All subjects who completed Part A elected to continue in Part B.
    Reporting group title
    BIVV009 6.5 g
    Reporting group description
    Subjects with primary CAD and body weight <75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All subjects who completed Part A elected to continue in Part B.

    Reporting group title
    BIVV009 7.5 g
    Reporting group description
    Subjects with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All subjects who completed Part A elected to continue in Part B.

    Subject analysis set title
    BIVV009
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects with primary CAD who had a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to enrollment) received an IV infusion of BIVV009 6.5 g (if body weight was <75 kg) or BIVV009 7.5 g (if body weight was >=75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Subjects who completed Part A per protocol through the end of treatment visit (Week 26) were eligible to be enrolled and continue to receive BIVV009 in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks.

    Primary: Part A: Percentage of Subjects With Response to Treatment

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    End point title
    Part A: Percentage of Subjects With Response to Treatment [1]
    End point description
    A subject was considered responder: if he or she did not receive blood transfusion from Week 5 through Week 26 (end of treatment in Part A) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, subject’s hemoglobin (Hgb) level had to meet either of the following criteria: Hgb level >=12 g/dL at treatment assessment endpoint (defined as average of values from Week 23, 25, and 26 visits), or Hgb increased >=2 g/dL from baseline (defined as last Hgb value before administration of first dose of study drug) at treatment assessment endpoint. Percentage of responders was calculated together with a 95% exact Clopper-Pearson confidence interval (CI). Analysis was performed on Part A- full analysis set (FAS) which included all subjects who received at least 1 dose (including partial dose) of study drug. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Primary
    End point timeframe
    From Week 5 through Week 26
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint was descriptive in nature, no statistical analysis was reported.
    End point values
    BIVV009
    Number of subjects analysed
    24
    Units: percentage of subjects
        number (confidence interval 95%)
    54.2 (32.8 to 74.4)
    No statistical analyses for this end point

    Primary: Part B: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

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    End point title
    Part B: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [2]
    End point description
    An Adverse Event (AE): any untoward medical occurrence in subject who received study drug and did not necessarily had to have a causal relationship with treatment. TESAEs was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs: AEs that developed, worsened or became serious during treatment-emergent (TE) period (from the first investigational medicinal product [IMP] administration in Part B to the last IMP administration + 9 weeks follow up [FU] period). Part B safety analysis set (SAS) which included all subjects who received at least 1 dose (including partial dose) of study drug in Part B. Data for this endpoint was planned to be collected and analysed for dose-wise reporting groups (BIVV009 6.5 g and BIVV009 7.5 g).
    End point type
    Primary
    End point timeframe
    Part B, 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks of FU (i.e., up to Week 179); Part B, 7.5 g cohort: From first dose (Week 27) up to 149 weeks of treatment + 9 weeks of FU (i.e., up to Week 185)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint was descriptive in nature, no statistical analysis was reported.
    End point values
    BIVV009 6.5 g BIVV009 7.5 g
    Number of subjects analysed
    16
    6
    Units: subjects
        TEAEs
    16
    6
        TESAEs
    10
    2
    No statistical analyses for this end point

    Secondary: Part A: Mean Change From Baseline in Bilirubin Levels at the Treatment Assessment Timepoint

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    End point title
    Part A: Mean Change From Baseline in Bilirubin Levels at the Treatment Assessment Timepoint
    End point description
    Mean change from baseline (Week 0) in bilirubin levels at the treatment assessment timepoint is reported in this endpoint. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. Least squares (LS) mean and 95% confidence interval (CI) was assessed by Mixed Model for Repeated Measures (MMRM) approach using heterogeneous Toeplitz (TOEPH) covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug. Analysis was performed on Part A-FAS. Here, 'number of subjects analysed' = subjects with available data for this endpoint. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
    End point values
    BIVV009
    Number of subjects analysed
    14
    Units: micromoles per Litre (mcmol/L)
        least squares mean (confidence interval 95%)
    -38.18 (-42.52 to -33.84)
    No statistical analyses for this end point

    Secondary: Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Treatment Assessment Timepoint

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    End point title
    Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Treatment Assessment Timepoint
    End point description
    FACIT-Fatigue scale consists of 13 questions assessed using a 5-point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question were added to obtain a total score. Total score ranged from 0 to 52, with higher score indicating more fatigue. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline (Week 0) as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug. Analysis was performed on Part A-FAS. Here, 'number of subjects analysed' = subjects with available data for this endpoint. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
    End point values
    BIVV009
    Number of subjects analysed
    17
    Units: score on a scale
        least squares mean (confidence interval 95%)
    10.85 (8.00 to 13.70)
    No statistical analyses for this end point

    Secondary: Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint

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    End point title
    Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint
    End point description
    Mean change from baseline (Week 0) in LDH at the treatment assessment timepoint is reported in this endpoint. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug. Analysis was performed on Part A-FAS. Here, 'number of subjects analysed' = subjects with available data for this endpoint. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
    End point values
    BIVV009
    Number of subjects analysed
    17
    Units: units per litre
        least squares mean (confidence interval 95%)
    -126.95 (-218.47 to -35.42)
    No statistical analyses for this end point

    Secondary: Part A: Number of Blood Transfusions Per Subject

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    End point title
    Part A: Number of Blood Transfusions Per Subject
    End point description
    A subject was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the subject had symptoms of anemia or Hgb was <7 g/dL and the subject was asymptomatic. Number of transfusions after the first 5 weeks of study drug administration and up to Week 26 were reported in this endpoint. Analysis was performed on Part A-FAS. Here, 'number of subjects analysed' = subjects with available data for this endpoint. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    From Week 5 up to Week 26
    End point values
    BIVV009
    Number of subjects analysed
    23
    Units: blood transfusions per subject
        arithmetic mean (standard deviation)
    0.9 ± 2.75
    No statistical analyses for this end point

    Secondary: Part A: Number of Blood Units Transfused Per Subject

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    End point title
    Part A: Number of Blood Units Transfused Per Subject
    End point description
    A subject was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the subject had symptoms of anemia or Hgb was <7 g/dL and the subject was asymptomatic. Number of blood units transfused after the first 5 weeks of study drug administration and up to Week 26 were reported in this endpoint. Analysis was performed on Part A-FAS. Here, 'number of subjects analysed' = subjects with at least 1 transfusion. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    From Week 5 up to Week 26
    End point values
    BIVV009
    Number of subjects analysed
    6
    Units: blood units transfused per subject
        arithmetic mean (standard deviation)
    5.8 ± 8.47
    No statistical analyses for this end point

    Secondary: Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint

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    End point title
    Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint
    End point description
    Mean change from baseline (Week 0) in Hgb at treatment assessment timepoint is reported in this endpoint. Treatment assessment timepoint was defined as the average of the values from the Week 23, 25, and 26 visits. LS mean and 95% CI was assessed by MMRM approach using TOEPH covariance matrix with change from baseline as the dependent variable and baseline value and visits as independent variables. Baseline was defined as the last non-missing value prior to the first administration of study drug. Analysis was performed on Part A-FAS. Here, 'number of subjects analysed' = subjects with available data for this endpoint. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26)
    End point values
    BIVV009
    Number of subjects analysed
    17
    Units: g/dL
        least squares mean (confidence interval 95%)
    2.60 (0.74 to 4.46)
    No statistical analyses for this end point

    Secondary: Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points

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    End point title
    Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points
    End point description
    Change from baseline (Week 0) in Hgb levels at each specified time points is reported in this endpoint. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. End of treatment (ET) visit/safety follow up (SFU) visit was 9 weeks after administration of last dose (i.e., up to Week 185). Analysis was performed on Part B-FAS which included all subjects who enrolled in Part B study and received at least 1 dose (including partial dose) of study drug. Here, 'n' = subjects with available data for each specified category. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]). Here, '99999' is used as a space filler and denotes that standard deviation (SD) was not estimable since only one subject was available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 27, 29,31,33,35,37,39,41,43,45,47,49, 51,53,55,57,59,61,63,65,67,69,71,73,75,77,79,83,87,91, 95,99,103,107,111,115,119, 123,127,131,135,139,143, 147,151, 155,159,163,167,171,175 and ET/SFU Visit (up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: g/dL
    arithmetic mean (standard deviation)
        Week 27 (n=22)
    2.76 ± 2.20
        Week 29 (n=22)
    2.77 ± 2.20
        Week 31 (n=22)
    2.74 ± 1.96
        Week 33 (n=22)
    2.87 ± 1.97
        Week 35 (n=21)
    2.82 ± 2.10
        Week 37 (n=21)
    2.71 ± 2.08
        Week 39 (n=21)
    2.72 ± 2.26
        Week 41 (n=21)
    2.76 ± 2.24
        Week 43 (n=21)
    2.73 ± 2.06
        Week 45 (n=21)
    2.84 ± 2.21
        Week 47 (n=21)
    2.74 ± 1.95
        Week 49 (n=21)
    2.73 ± 2.09
        Week 51 (n=22)
    2.71 ± 1.97
        Week 53 (n=22)
    2.66 ± 1.97
        Week 55 (n=21)
    2.73 ± 1.96
        Week 57 (n=21)
    3.01 ± 2.36
        Week 59 (n=21)
    2.81 ± 2.10
        Week 61 (n=21)
    2.88 ± 2.37
        Week 63 (n=21)
    2.99 ± 2.33
        Week 65 (n=21)
    2.53 ± 2.18
        Week 67 (n=20)
    2.52 ± 2.20
        Week 69 (n=20)
    2.96 ± 2.08
        Week 71 (n=19)
    2.86 ± 2.31
        Week 73 (n=20)
    2.79 ± 2.25
        Week 75 (n=21)
    2.70 ± 2.18
        Week 77 (n=21)
    2.93 ± 2.59
        Week 79 (n=19)
    3.13 ± 2.23
        Week 83 (n=20)
    2.89 ± 2.47
        Week 87 (n=18)
    2.63 ± 2.36
        Week 91 (n=20)
    3.23 ± 2.17
        Week 95 (n=19)
    3.12 ± 2.06
        Week 99 (n=20)
    2.98 ± 2.01
        Week 103 (n=21)
    2.92 ± 2.09
        Week 107 (n=21)
    2.60 ± 2.10
        Week 111 (n=21)
    2.82 ± 2.17
        Week 115 (n=19)
    2.96 ± 2.25
        Week 119 (n=20)
    2.79 ± 2.57
        Week 123 (n=20)
    2.82 ± 2.35
        Week 127 (n=19)
    2.89 ± 1.99
        Week 131 (n=19)
    3.03 ± 2.19
        Week 135 (n=19)
    3.35 ± 1.99
        Week 139 (n=13)
    3.42 ± 2.14
        Week 143 (n=11)
    3.43 ± 2.31
        Week 147 (n=8)
    3.75 ± 2.38
        Week 151 (n=8)
    3.43 ± 1.91
        Week 155 (n=8)
    3.74 ± 1.94
        Week 159 (n=6)
    5.20 ± 1.65
        Week 163 (n=4)
    4.18 ± 1.14
        Week 167 (n=2)
    4.80 ± 0.42
        Week 171 (n=1)
    4.80 ± 99999
        Week 175 (n=1)
    4.40 ± 99999
        ET/SFU Visit (n=20)
    1.21 ± 1.56
    No statistical analyses for this end point

    Secondary: Part B: Change From Baseline in Bilirubin Levels at Each Specified Time Points

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    End point title
    Part B: Change From Baseline in Bilirubin Levels at Each Specified Time Points
    End point description
    Change from baseline (Week 0) in bilirubin levels at each specified time point is reported in this endpoint. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Analysis was performed on Part B-FAS. Here, ‘number of subjects analysed’ = subjects with available data for this endpoint and ‘n’ = subjects with available data for each specified category. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]). Here, '99999' is used as a space filler and denotes that SD was not estimable since only one subject was available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 27, 29,31,33,35,37,39,41,43,45,47,49, 51,53,55,57,59,61,63,65,67,69,71,73,75,77,79,83,87,91, 95,99,103,107,111,115,119, 123,127,131,135,139,143, 147,151, 155,159,163,167,171,175 and ET/SFU Visit (up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    19
    Units: mcmol/L
    arithmetic mean (standard deviation)
        Week 27 (n=19)
    -34.96 ± 18.31
        Week 29 (n=19)
    -34.92 ± 15.78
        Week 31 (n=19)
    -32.58 ± 17.07
        Week 33 (n=19)
    -32.67 ± 17.52
        Week 35 (n=19)
    -32.25 ± 22.39
        Week 37 (n=19)
    -33.24 ± 15.53
        Week 39 (n=13)
    -35.92 ± 13.17
        Week 41 (n=18)
    -35.03 ± 13.71
        Week 43 (n=16)
    -36.46 ± 17.25
        Week 45 (n=18)
    -34.81 ± 15.76
        Week 47 (n=18)
    -34.57 ± 16.53
        Week 49 (n=18)
    -32.36 ± 19.50
        Week 51 (n=16)
    -34.88 ± 15.90
        Week 53 (n=19)
    -35.25 ± 18.32
        Week 55 (n=18)
    -34.79 ± 16.70
        Week 57 (n=18)
    -36.32 ± 16.54
        Week 59 (n=18)
    -35.77 ± 17.73
        Week 61 (n=18)
    -36.39 ± 16.14
        Week 63 (n=17)
    -38.25 ± 15.43
        Week 65 (n=17)
    -35.46 ± 16.84
        Week 67 (n=17)
    -35.74 ± 18.37
        Week 69 (n=17)
    -33.88 ± 16.83
        Week 71 (n=17)
    -32.54 ± 23.01
        Week 73 (n=14)
    -33.03 ± 21.82
        Week 75 (n=16)
    -30.55 ± 21.68
        Week 77 (n=18)
    -30.95 ± 22.83
        Week 79 (n=17)
    -35.51 ± 14.79
        Week 83 (n=16)
    -38.60 ± 13.90
        Week 87 (n=15)
    -37.45 ± 16.29
        Week 91 (n=16)
    -35.19 ± 16.07
        Week 95 (n=15)
    -33.57 ± 15.93
        Week 99 (n=15)
    -28.71 ± 21.98
        Week 103 (n=18)
    -32.04 ± 22.45
        Week 107 (n=18)
    -34.46 ± 15.27
        Week 111 (n=15)
    -37.67 ± 14.28
        Week 115 (n=16)
    -36.41 ± 16.76
        Week 119 (n=16)
    -34.65 ± 13.71
        Week 123 (n=17)
    -29.99 ± 24.96
        Week 127 (n=17)
    -35.57 ± 17.83
        Week 131 (n=16)
    -35.03 ± 18.72
        Week 135 (n=15)
    -36.88 ± 14.71
        Week 139 (n=11)
    -37.60 ± 14.59
        Week 143 (n=8)
    -44.50 ± 15.96
        Week 147 (n=6)
    -44.82 ± 15.12
        Week 151 (n=6)
    -46.53 ± 10.80
        Week 155 (n=6)
    -50.32 ± 12.63
        Week 159 (n=5)
    -46.30 ± 13.90
        Week 163 (n=4)
    -46.13 ± 11.86
        Week 167 (n=2)
    -36.30 ± 12.59
        Week 171 (n=1)
    -32.50 ± 99999
        Week 175 (n=1)
    -29.10 ± 99999
        ET/SFU Visit (n=17)
    -9.98 ± 18.11
    No statistical analyses for this end point

    Secondary: Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points

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    End point title
    Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points
    End point description
    FACIT-Fatigue scale consists of 13 questions assessed using a 5-point scale (0=not at all; 1 = a little bit, 2 = somewhat, 3 = quite a bit and 4 = very much). Responses to each question were added to obtain a total score. The Total score ranged from 0 to 52, with higher score indicating more fatigue. Baseline (Week 0) was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Analysis was performed on Part B-FAS. Here, ‘n’ = subjects with available data for each specified category. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]). Here, '99999' is used as a space filler and denotes that SD was not estimable due to only one subject being available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and ET Visit/SFU visit (i.e., up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 39 (n=19)
    9.37 ± 16.00
        Week 51 (n=20)
    10.50 ± 12.05
        Week 63 (n=19)
    10.21 ± 11.88
        Week 75 (n=19)
    11.00 ± 11.51
        Week 87 (n=18)
    10.39 ± 13.41
        Week 99 (n=17)
    9.94 ± 8.19
        Week 111 (n=18)
    9.11 ± 12.35
        Week 123 (n=19)
    6.79 ± 11.28
        Week 135 (n=14)
    11.71 ± 13.85
        Week 147 (n=7)
    13.29 ± 13.39
        Week 159 (n=4)
    24.75 ± 10.24
        Week 171 (n=1)
    32.00 ± 99999
        ET/SFU Visit (n=19)
    1.05 ± 8.15
    No statistical analyses for this end point

    Secondary: Part B: Change From Baseline in 12-Item Short-Form Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Each Specified Time Points

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    End point title
    Part B: Change From Baseline in 12-Item Short-Form Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Each Specified Time Points
    End point description
    SF-12: 12 item-questionnaire contained 12 items, categorised into 8 domains (subscales) of functioning & well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality & social functioning, with each domain score ranged from 0 (poor health) to 100 (better health). Higher scores = good health condition. These 8 domains were further summarised into 2 summary scores, PCS and MCS for which score ranged from 0 (poor health) to 100 (better health). Higher scores = better HRQOL. Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Part B-FAS. Here, 'n' = subjects with available data. Data for this endpoint was planned to be collected & analysed for combined population (i.e., either 6.5 g or 7.5 g). '99999' = space filler which denotes SD was not estimable since only one subject was available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135 and ET Visit/SFU visit (i.e., up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 39-PCS (n=16)
    7.813 ± 10.486
        Week 39-MCS (n=16)
    5.859 ± 10.249
        Week 51-PCS (n=18)
    6.677 ± 9.925
        Week 51-MCS (n=18)
    3.912 ± 9.493
        Week 63-PCS (n=19)
    8.318 ± 7.148
        Week 63-MCS (n=19)
    2.385 ± 9.777
        Week 75-PCS (n=18)
    6.580 ± 9.214
        Week 75-MCS (n=18)
    3.102 ± 9.881
        Week 87-PCS (n=18)
    6.398 ± 9.021
        Week 87-MCS (n=18)
    1.611 ± 10.336
        Week 99-PCS (n=14)
    9.054 ± 5.803
        Week 99-MCS (n=14)
    2.581 ± 9.169
        Week 111-PCS (n=8)
    11.958 ± 3.832
        Week 111-MCS (n=8)
    2.523 ± 12.585
        Week 123-PCS (n=6)
    4.743 ± 6.900
        Week 123-MCS (n=6)
    3.810 ± 14.071
        Week 135-PCS (n=1)
    10.450 ± 99999
        Week 135-MCS (n=1)
    27.900 ± 99999
        ET/SFU Visit-PCS (n=1)
    -8.920 ± 99999
        ET/SFU Visit-MCS (n=1)
    -1.180 ± 99999
    No statistical analyses for this end point

    Secondary: Part B: Change From Baseline in 5-level European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Health State Utility Index and VAS Scores at Each Specified Time Points

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    End point title
    Part B: Change From Baseline in 5-level European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) Health State Utility Index and VAS Scores at Each Specified Time Points
    End point description
    EQ-5D-5L: subject-rated questionnaire included 2 components: health state utility index (descriptive) & Visual Analog Scale (VAS). EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response option: no, slight, moderate, severe & extreme problems measured with Likert scale. EQ-5D-5L responses converted into single index utility score between 0 to 1. Higher score=better health . EQ-5D-5L VAS rated subject’s current health state on scale from 0(worst imaginable health) to 100 (best imaginable health). Baseline (Week 0): last non-missing value prior to first administration of study drug in Part A. ET visit/SFU visit: 9 weeks after administration of last dose (i.e., up to Week 185). Part B FAS. Data was planned to be collected & analysed for combined population. 'n'= subjects with available data. '99999'; space filler which denotes that SD was not estimable since only 1 subject was available.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 39 - Index score (n=18)
    0.067 ± 0.264
        Week 39 - VAS score (n=18)
    18.111 ± 20.642
        Week 51 - Index score (n=20)
    0.078 ± 0.194
        Week 51 - VAS score (n=20)
    14.500 ± 19.050
        Week 63 - Index score (n=19)
    0.092 ± 0.166
        Week 63 - VAS score (n=19)
    18.053 ± 16.844
        Week 75 - Index score (n=19)
    0.069 ± 0.211
        Week 75 - VAS score (n=19)
    17.842 ± 16.604
        Week 87 - Index score (n=19)
    0.022 ± 0.226
        Week 87 - VAS score (n=19)
    14.421 ± 20.815
        Week 99 - Index Score (n=17)
    0.060 ± 0.136
        Week 99 - VAS Score (n=17)
    14.059 ± 13.818
        Week 111 - Index score (n=18)
    0.099 ± 0.174
        Week 111 - VAS score (n=18)
    18.889 ± 15.408
        Week 123 - Index Score (n=19)
    0.009 ± 0.190
        Week 123 - VAS score (n=19)
    8.842 ± 18.765
        Week 135 - Index score (n=15)
    0.085 ± 0.233
        Week 135 - VAS score (n=15)
    17.067 ± 21.608
        Week 147 - Index score (n=7)
    0.143 ± 0.131
        Week 147 - VAS score (n=7)
    17.857 ± 20.178
        Week 159 - Index Score (n=4)
    0.250 ± 0.145
        Week 159 - VAS Score (n=4)
    36.250 ± 14.930
        Week 171 - Index score (n=1)
    0.535 ± 99999
        Week 171 - VAS score (n=1)
    35.000 ± 99999
        ET/SFU - Index score (n=19)
    -0.025 ± 0.173
        ET/SFU - VAS score (n=19)
    1.263 ± 19.287
    No statistical analyses for this end point

    Secondary: Part B: Number of Subjects With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points

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    End point title
    Part B: Number of Subjects With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points
    End point description
    The PGIS is a self-reported scale. The PGIS is a 1-item questionnaire designed to assess subject’s impression of disease severity using a 5-point scale ranging from 1 to 5, where 1=none, 2=mild, 3=moderate, 4=severe, 5=very severe. Higher scores indicated greater severity. Analysis was performed on Part B-FAS population. Here, ‘n’ = subjects with available data for each specified category. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: subjects
        Week 39 - None (n=18)
    5
        Week 39 - Mild (n=18)
    8
        Week 39 - Moderate (n=18)
    4
        Week 39 - Severe (n=18)
    1
        Week 39 - Very severe (n=18)
    0
        Week 51 - None (n=21)
    5
        Week 51 - Mild (n=21)
    13
        Week 51 - Moderate (n=21)
    3
        Week 51 - Severe (n=21)
    0
        Week 51 - Very severe (n=21)
    0
        Week 63 - None (n=20)
    4
        Week 63 - Mild (n=20)
    12
        Week 63 - Moderate (n=20)
    3
        Week 63 - Severe (n=20)
    1
        Week 63 - Very severe (n=20)
    0
        Week 75 - None (n=20)
    3
        Week 75 - Mild (n=20)
    12
        Week 75 - Moderate (n=20)
    5
        Week 75 - Severe (n=20)
    0
        Week 75 - Very severe (n=20)
    0
        Week 87 - None (n=19)
    5
        Week 87 - Mild (n=19)
    9
        Week 87 - Moderate (n=19)
    3
        Week 87 - Severe (n=19)
    2
        Week 87 - Very severe (n=19)
    0
        Week 99 - None (n=18)
    4
        Week 99 - Mild (n=18)
    10
        Week 99 - Moderate (n=18)
    4
        Week 99 - Severe (n=18)
    0
        Week 99 - Very severe (n=18)
    0
        Week 111 - None (n=19)
    7
        Week 111 - Mild (n=19)
    6
        Week 111 - Moderate (n=19)
    6
        Week 111 - Severe (n=19)
    0
        Week 111 - Very severe (n=19)
    0
        Week 123 - None (n=20)
    4
        Week 123 - Mild (n=20)
    7
        Week 123 - Moderate (n=20)
    7
        Week 123 - Severe (n=20)
    2
        Week 123 - Very severe (n=20)
    0
        Week 135 - None (n=15)
    4
        Week 135 - Mild (n=15)
    8
        Week 135 - Moderate (n=15)
    3
        Week 135 - Severe (n=15)
    0
        Week 135 - Very severe (n=15)
    0
        Week 147 - None (n=7)
    3
        Week 147 - Mild (n=7)
    3
        Week 147 - Moderate (n=7)
    1
        Week 147 - Severe (n=7)
    0
        Week 147 - Very severe (n=7)
    0
        Week 159 - None (n=4)
    3
        Week 159 - Mild (n=4)
    1
        Week 159 - Moderate (n=4)
    0
        Week 159 - Severe (n=4)
    0
        Week 159 - Very severe (n=4)
    0
        Week 171 - None (n=1)
    0
        Week 171 - Mild (n=1)
    1
        Week 171 - Moderate (n=1)
    0
        Week 171 - Severe (n=1)
    0
        Week 171 - Very severe (n=1)
    0
        ET/SFU - None (n=20)
    4
        ET/SFU - Mild (n=20)
    6
        ET/SFU - Moderate (n=20)
    4
        ET/SFU - Severe (n=20)
    5
        ET/SFU - Very severe (n=20)
    1
    No statistical analyses for this end point

    Secondary: Part B: Number of Subjects With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points

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    End point title
    Part B: Number of Subjects With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points
    End point description
    PGIC is a self-administered questionnaire to evaluate the improvement or worsening compared to the start of the study. PGIC was assessed on a 7-point Likert scale ranged from 1 (greatly improved) to 7 (greatly worsened). Categories were defined based on the PGIC scores as follows: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse and 7=very much worsen. Higher scores indicated greater severity. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Analysis was performed on Part B-FAS. Here, 'n' = subjects with available data for each specified category. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    At Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147,159, 171 and at ET Visit/SFU visit (i.e., up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: subjects
        Week 39 - Very much improved (n=19)
    9
        Week 39 - Much improved (n=19)
    5
        Week 39 - Minimally improved (n=19)
    3
        Week 39 - No change (n=19)
    1
        Week 39 - Minimally worse (n=19)
    0
        Week 39 - Much worse (n=19)
    1
        Week 39 - Very much worse (n=19)
    0
        Week 51 - Very much improved (n=21)
    6
        Week 51 - Much improved (n=21)
    13
        Week 51 - Minimally improved (n=21)
    2
        Week 51 - No change (n=21)
    0
        Week 51 - Minimally worse (n=21)
    0
        Week 51 - Much worse (n=21)
    0
        Week 51- Very much worse (n=21)
    0
        Week 63 - Very much improved (n=20)
    8
        Week 63 - Much improved (n=20)
    9
        Week 63 - Minimally improved (n=20)
    1
        Week 63 - No change (n=20)
    1
        Week 63 - Minimally worse (n=20)
    1
        Week 63 - Much worse (n=20)
    0
        Week 63 - Very much worse (n=20)
    0
        Week 75 - Very much improved (n=20)
    5
        Week 75 - Much improved (n=20)
    11
        Week 75 - Minimally improved (n=20)
    1
        Week 75 - No change (n=20)
    2
        Week 75 - Minimally worse (n=20)
    1
        Week 75 - Much worse (n=20)
    0
        Week 75 - Very much worse (n=20)
    0
        Week 87 - Very much improved (n=19)
    5
        Week 87 - Much improved (n=19)
    11
        Week 87 - Minimally improved (n=19)
    2
        Week 87 - No change (n=19)
    1
        Week 87 - Minimally worse (n=19)
    0
        Week 87 - Much worse (n=19)
    0
        Week 87 - Very much worse (n=19)
    0
        Week 99 - Very much improved (n=18)
    4
        Week 99 - Much improved (n=18)
    10
        Week 99 - Minimally improved (n=18)
    3
        Week 99 - No Change (n=18)
    1
        Week 99 - Minimally worse (n=18)
    0
        Week 99 - Much worse (n=18)
    0
        Week 99 - Very much worse (n=18)
    0
        Week 111 - Very much improved (n=19)
    7
        Week 111 - Much improved (n=19)
    7
        Week 111 - Minimally improved (n=19)
    5
        Week 111 - No change (n=19)
    0
        Week 111 - Minimally worse (n=19)
    0
        Week 111 - Much worse (n=19)
    0
        Week 111 - Very much worse (n=19)
    0
        Week 123 - Very much improved (n=20)
    8
        Week 123 - Much improved (n=20)
    6
        Week 123 - Minimally improved (n=20)
    6
        Week 123 - No change (n=20)
    0
        Week 123 - Minimally worse (n=20)
    0
        Week 123 - Much worse (n=20)
    0
        Week 123 - Very much worse (n=20)
    0
        Week 135 - Very much improved (n=15)
    5
        Week 135 - Much improved (n=15)
    6
        Week 135 - Minimally improved (n=15)
    2
        Week 135 - No change (n=15)
    1
        Week 135 - Minimally worse (n=15)
    1
        Week 135 - Much worse (n=15)
    0
        Week 135 - Very much worse (n=15)
    0
        Week 147 - Very much improved (n=7)
    4
        Week 147 - Much improved (n=7)
    2
        Week 147 - Minimally improved (n=7)
    1
        Week 147 - No change (n=7)
    0
        Week 147 - Minimally worse (n=7)
    0
        Week 147 - Much worse (n=7)
    0
        Week 147 - Very much worse (n=7)
    0
        Week 159 - Very much improved (n=4)
    4
        Week 159 - Much improved (n=4)
    0
        Week 159 - Minimally improved (n=4)
    0
        Week 159 - No change (n=4)
    0
        Week 159 - Minimally worse (n=4)
    0
        Week 159 - Much worse (n=4)
    0
        Week 159 - Very much worse (n=4)
    0
        Week 171 - Very much improved (n=1)
    1
        Week 171 - Much improved (n=1)
    0
        Week 171 - Minimally improved (n=1)
    0
        Week 171 - No Change (n=1)
    0
        Week 171 - Minimally worse (n=1)
    0
        Week 171 - Much worse (n=1)
    0
        Week 171 - Very much worse (n=1)
    0
        ET/SFU Visit- Very much improved (n=20)
    3
        ET/SFU Visit- Much improved (n=20)
    8
        ET/SFU Visit- Minimally improved (n=20)
    2
        ET/SFU Visit- No Change (n=20)
    4
        ET/SFU Visit- Minimally worse (n=20)
    2
        ET/SFU Visit- Much worse (n=20)
    0
        ET/SFU Visit- Very much worse (n=20)
    1
    No statistical analyses for this end point

    Secondary: Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points

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    End point title
    Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points
    End point description
    Mean change from baseline (Week 0) in LDH levels at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this endpoint. Baseline was defined as the last non-missing value prior to the first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Analysis was performed on Part B-FAS. Here, 'n' = subjects with available data for each specified category. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]). Here, '99999' is used as a space filler and denotes that SD was not estimable since only one subject was available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 27,29,31,33,35,37,39,41,43,45,47,49,51,53,55,57,59,61,63,65,67,69, 71,73,75,77,79,83,87,91,95,99,103,107,111,115,119,123,127,131,135,139,143,147,151,155, 159,163,167,171,175 and ET/SFU Visit (up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: units per litre
    arithmetic mean (standard deviation)
        Week 27 (n=22)
    -111.59 ± 327.80
        Week 29 (n=21)
    -129.76 ± 331.91
        Week 31 (n=22)
    -95.27 ± 319.25
        Week 33 (n=21)
    -82.19 ± 330.04
        Week 35 (n=22)
    -126.64 ± 346.75
        Week 37 (n=21)
    -151.57 ± 307.15
        Week 39 (n=15)
    -49.27 ± 172.53
        Week 41 (n=21)
    -116.10 ± 305.11
        Week 43 (n=19)
    -150.26 ± 271.72
        Week 45 (n=21)
    -85.48 ± 308.01
        Week 47 (n=21)
    -79.81 ± 286.13
        Week 49 (n=21)
    -104.38 ± 313.66
        Week 51 (n=19)
    -76.84 ± 344.60
        Week 53 (n=21)
    -87.00 ± 299.09
        Week 55 (n=21)
    -68.29 ± 305.09
        Week 57 (n=21)
    -101.71 ± 273.44
        Week 59 (n=21)
    -97.71 ± 296.74
        Week 61 (n=21)
    -89.48 ± 298.05
        Week 63 (n=20)
    -94.20 ± 288.34
        Week 65 (n=20)
    -91.05 ± 305.75
        Week 67 (n=19)
    -106.32 ± 327.48
        Week 69 (n=19)
    -75.00 ± 333.47
        Week 71 (n=18)
    -52.39 ± 378.82
        Week 73 (n=17)
    -70.35 ± 348.56
        Week 75 (n=19)
    -18.68 ± 323.02
        Week 77 (n=21)
    -64.67 ± 335.73
        Week 79 (n=20)
    -54.10 ± 338.58
        Week 83 (n=19)
    -87.21 ± 344.88
        Week 87 (n=18)
    -89.17 ± 392.80
        Week 91 (n=19)
    -78.47 ± 349.15
        Week 95 (n=16)
    -132.75 ± 301.36
        Week 99 (n=18)
    -13.83 ± 155.04
        Week 103 (n=20)
    106.40 ± 309.44
        Week 107 (n=20)
    -85.45 ± 312.50
        Week 111 (n=19)
    -107.58 ± 286.18
        Week 115 (n=19)
    -107.84 ± 293.61
        Week 119 (n=19)
    -63.68 ± 310.56
        Week 123 (n=20)
    -58.90 ± 339.49
        Week 127 (n=18)
    -57.72 ± 400.26
        Week 131 (n=19)
    -113.63 ± 344.53
        Week 135 (n=17)
    -97.06 ± 339.41
        Week 139 (n=13)
    -1.00 ± 256.65
        Week 143 (n=10)
    180.70 ± 318.62
        Week 147 (n=7)
    -10.29 ± 196.90
        Week 151 (n=8)
    -24.13 ± 146.79
        Week 155 (n=8)
    -17.38 ± 146.80
        Week 159 (n=4)
    -126.00 ± 150.38
        Week 163 (n=4)
    -31.50 ± 35.49
        Week 167 (n=2)
    -48.50 ± 68.59
        Week 171 (n=1)
    -23.00 ± 99999
        Week 175 (n=1)
    6.00 ± 99999
        ET/SFU visit (n=20)
    -107.50 ± 249.28
    No statistical analyses for this end point

    Secondary: Part B: Number of Blood Transfusions Per Subject

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    End point title
    Part B: Number of Blood Transfusions Per Subject
    End point description
    A subject was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the subject had symptoms of anemia or Hgb was <7 g/dL and the subject was asymptomatic. Analysis was performed on Part B-FAS. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: blood transfusions per subject
        arithmetic mean (standard deviation)
    2.86 ± 6.58
    No statistical analyses for this end point

    Secondary: Part B: Number of Blood Units Transfused Per Subject

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    End point title
    Part B: Number of Blood Units Transfused Per Subject
    End point description
    A subject was to receive a transfusion if his or her Hgb level met either of the following criteria: Hgb was <9 g/dL and the subject had symptoms of anemia or Hgb was <7 g/dL and the subject was asymptomatic. Analysis was performed on Part B-FAS. Here, 'number of subjects analysed' = subjects with at least 1 transfusion. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either at 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
    End point values
    BIVV009
    Number of subjects analysed
    7
    Units: blood units transfused per subject
        arithmetic mean (standard deviation)
    16.57 ± 16.85
    No statistical analyses for this end point

    Secondary: Part B: Change From Baseline in Haptoglobin Values at Each Specified Time Points

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    End point title
    Part B: Change From Baseline in Haptoglobin Values at Each Specified Time Points
    End point description
    Change from baseline (Week 0) in haptoglobin values at each specified time points (i.e., Weeks 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 83, 87, 91, 95, 99, 103, 107, 111, 115, 119, 123, 127, 131, 135, 139, 143, 147, 151, 155, 159, 163, 167, 171, 175 and ET/SFU Visit) is reported in this endpoint. Baseline was defined as the last non-missing value prior to thez first administration of study drug in Part A. ET visit/SFU visit was 9 weeks after administration of last dose (i.e., up to Week 185). Haptoglobin values <0.2 were imputed as 0.2. Part B-FAS. Here, 'n' = subjects with available data for each specified category. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either at 6.5 g or 7.5 g]). Here, '99999' is used as a space filler and denotes that standard deviation was not estimable since only one subject was available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline (Week 0), Weeks 27, 29,31,33,35,37,39,41,43,45,47,49, 51,53,55,57,59,61,63,65,67,69,71,73,75,77,79,83,87,91, 95,99,103,107,111,115,119, 123,127,131,135,139,143, 147,151, 155,159,163,167,171,175 and ET/SFU Visit (up to Week 185)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: grams per litre
    arithmetic mean (standard deviation)
        Week 27 (n=22)
    0.21 ± 0.38
        Week 29 (n=21)
    0.21 ± 0.45
        Week 31 (n=22)
    0.21 ± 0.43
        Week 33 (n=22)
    0.28 ± 0.53
        Week 35 (n=22)
    0.25 ± 0.41
        Week 37 (n=21)
    0.14 ± 0.28
        Week 39 (n=17)
    0.27 ± 0.49
        Week 41 (n=20)
    0.39 ± 0.59
        Week 43 (n=18)
    0.29 ± 0.47
        Week 45 (n=21)
    0.16 ± 0.26
        Week 47 (n=20)
    0.15 ± 0.35
        Week 49 (n=21)
    0.21 ± 0.41
        Week 51 (n=19)
    0.20 ± 0.37
        Week 53 (n=22)
    0.23 ± 0.46
        Week 55 (n=20)
    0.26 ± 0.45
        Week 57 (n=20)
    0.26 ± 0.43
        Week 59 (n=21)
    0.29 ± 0.44
        Week 61 (n=21)
    0.23 ± 0.43
        Week 63 (n=20)
    0.38 ± 0.50
        Week 65 (n=20)
    0.25 ± 0.41
        Week 67 (n=19)
    0.25 ± 0.42
        Week 69 (n=20)
    0.24 ± 0.47
        Week 71 (n=19)
    0.19 ± 0.33
        Week 73 (n=19)
    0.13 ± 0.29
        Week 75 (n=20)
    0.13 ± 0.24
        Week 77 (n=21)
    0.17 ± 0.29
        Week 79 (n=20)
    0.09 ± 0.22
        Week 83 (n=20)
    0.14 ± 0.25
        Week 87 (n=18)
    0.35 ± 0.53
        Week 91 (n=19)
    0.17 ± 0.28
        Week 95 (n=20)
    0.19 ± 0.33
        Week 99 (n=18)
    0.21 ± 0.37
        Week 103 (n=21)
    0.15 ± 0.25
        Week 107 (n=21)
    0.26 ± 0.40
        Week 111 (n=19)
    0.22 ± 0.33
        Week 115 (n=18)
    0.21 ± 0.35
        Week 119 (n=19)
    0.16 ± 0.31
        Week 123 (n=20)
    0.19 ± 0.45
        Week 127 (n=20)
    0.14 ± 0.23
        Week 131 (n=19)
    0.18 ± 0.38
        Week 135 (n=18)
    0.18 ± 0.35
        Week 139 (n=13)
    0.10 ± 0.17
        Week 143 (n=11)
    0.07 ± 0.16
        Week 147 (n=8)
    0.06 ± 0.16
        Week 151 (n=8)
    0.12 ± 0.24
        Week 155 (n=8)
    0.09 ± 0.22
        Week 159 (n=5)
    0.15 ± 0.34
        Week 163 (n=4)
    0.30 ± 0.35
        Week 167 (n=2)
    0.00 ± 0.00
        Week 171 (n=1)
    0.00 ± 99999
        Week 175 (n=1)
    0.00 ± 99999
        ET/SFU visit (n=20)
    0.02 ± 0.13
    No statistical analyses for this end point

    Secondary: Part B: Number of Healthcare Visits by Type

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    End point title
    Part B: Number of Healthcare Visits by Type
    End point description
    In this endpoint, number of healthcare visits which included non-study healthcare resource utilisation visit (consisted mainly of extra visits to the office of the study doctor, visit to a generalist doctor or visit to a specialist doctor), hospitalisation visit and visit to hospital emergency is reported. Analysis was performed on Part B-FAS. Data for this endpoint was planned to be collected and analysed for combined population (i.e., all subjects who received BIVV009 [either 6.5 g or 7.5 g]).
    End point type
    Secondary
    End point timeframe
    From Week 27 up to 149 weeks of treatment (i.e., up to Week 176)
    End point values
    BIVV009
    Number of subjects analysed
    22
    Units: visits
    number (not applicable)
        Non-study healthcare resource utilisation visits
    16
        Hospitalisation
    8
        Visit to a hospital emergency room
    3
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Part A: From first dose (Day 0) up to Week 26; Part B: 6.5 g cohort: From first dose (Week 27) up to 143 weeks of treatment + 9 weeks FU (i.e., up to Week 179); 7.5 g cohort: From first dose up to 149 weeks of treatment + 9 weeks FU (i.e., up to Week 185)
    Adverse event reporting additional description
    Reported AEs and SAEs including fatal AEs were TEAEs that developed/worsened or became serious during on-treatment period. Analysis was performed on SAS.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Part A: BIVV009 6.5 g
    Reporting group description
    Subjects with primary CAD and body weight <75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 6.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25.

    Reporting group title
    Part A: BIVV009 7.5 g
    Reporting group description
    Subjects with primary CAD and body weight >=75 kg with a recent history of blood transfusion (defined as at least 1 transfusion during the last 6 months prior to screening in this study) received an IV infusion of BIVV009 7.5 g on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25.

    Reporting group title
    Part B: BIVV009 6.5 g
    Reporting group description
    Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 6.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 143 weeks. All subjects who completed Part A elected to continue in Part B.

    Reporting group title
    Part B: BIVV009 7.5 g
    Reporting group description
    Subjects who completed Part A per protocol through the end of treatment visit (Week 26) could continue to receive BIVV009 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks. All subjects who completed Part A elected to continue in Part B.

    Serious adverse events
    Part A: BIVV009 6.5 g Part A: BIVV009 7.5 g Part B: BIVV009 6.5 g Part B: BIVV009 7.5 g
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 17 (23.53%)
    3 / 7 (42.86%)
    10 / 16 (62.50%)
    2 / 6 (33.33%)
         number of deaths (all causes)
    0
    1
    2
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatic Cancer
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal Cell Carcinoma
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tubular Breast Carcinoma
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Cyanosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Vascular Disorder
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral Artery Thrombosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Inflammation
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femoral Neck Fracture
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina Pectoris
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary Artery Stenosis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stress Cardiomyopathy
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Parkinsonism
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient Global Amnesia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cold Type Haemolytic Anaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Haemolytic Anaemia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Iridocyclitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal Detachment
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uveitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vitreous Haemorrhage
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Haemorrhage
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal Hernia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis Acute
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Biliary Colic
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary Retention
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Asymptomatic Covid-19
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Covid-19 Pneumonia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia Sepsis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes Zoster
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumococcal Sepsis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Klebsiella
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Streptococcal Sepsis
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection Bacterial
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound Infection Staphylococcal
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Part A: BIVV009 6.5 g Part A: BIVV009 7.5 g Part B: BIVV009 6.5 g Part B: BIVV009 7.5 g
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 17 (88.24%)
    6 / 7 (85.71%)
    16 / 16 (100.00%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal Cell Carcinoma
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    1
    0
    Bowen's Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Myelodysplastic Syndrome
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Seborrhoeic Keratosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vascular disorders
    Fibromuscular Dysplasia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Essential Hypertension
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cyanosis
         subjects affected / exposed
    2 / 17 (11.76%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    2 / 6 (33.33%)
         occurrences all number
    3
    0
    3
    4
    Circulatory Collapse
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Air Embolism
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypertension
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    3 / 16 (18.75%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    6
    3
    Hot Flush
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Haematoma
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    4
    1
    Catheter Site Haematoma
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Drug Intolerance
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Device Related Thrombosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chest Discomfort
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Mucosal Inflammation
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Malaise
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Influenza Like Illness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Facial Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Fatigue
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    3 / 16 (18.75%)
    3 / 6 (50.00%)
         occurrences all number
    1
    0
    3
    5
    Feeling Cold
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Oedema Peripheral
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    2
    2
    Peripheral Swelling
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    3 / 16 (18.75%)
    2 / 6 (33.33%)
         occurrences all number
    0
    1
    4
    4
    Temperature Intolerance
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Immune system disorders
    Allergy To Arthropod Bite
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Seasonal Allergy
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Autoinflammatory Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Reproductive system and breast disorders
    Benign Prostatic Hyperplasia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Intermenstrual Bleeding
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ovarian Cyst
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pelvic Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Bronchial Irritation
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Cough
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Dyspnoea Exertional
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    2
    Dyspnoea
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    1
    2
    Epistaxis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    7
    0
    6
    0
    Restrictive Pulmonary Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Respiratory Tract Congestion
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Productive Cough
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    0
    1
    Pleural Effusion
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Nasal Congestion
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sputum Discoloured
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Sleep Apnoea Syndrome
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Psychiatric disorders
    Anxiety Disorder
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Confusional State
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    3
    0
    Insomnia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Adjustment Disorder
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Mental Fatigue
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Blood Creatinine Increased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood Immunoglobulin G Decreased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood Pressure Increased
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    C-Reactive Protein Increased
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Chest X-Ray Abnormal
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Computerised Tomogram Head Abnormal
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Serum Ferritin Decreased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Weight Increased
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Ankle Fracture
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Arthropod Bite
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Back Injury
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Bone Contusion
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Concussion
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Exposure To Extreme Temperature
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Eye Contusion
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hand Fracture
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Fall
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    3
    1
    1
    1
    Infusion Related Reaction
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Joint Injury
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Limb Injury
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Procedural Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Road Traffic Accident
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Skin Abrasion
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Spinal Column Injury
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Stress Fracture
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Tendon Rupture
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Cardiac disorders
    Aortic Valve Incompetence
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Aortic Valve Sclerosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Aortic Valve Stenosis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Atrial Fibrillation
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Atrioventricular Block First Degree
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Cardiac Failure
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Coronary Artery Disease
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Sinus Bradycardia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Mitral Valve Incompetence
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Stress Cardiomyopathy
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Supraventricular Extrasystoles
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tricuspid Valve Incompetence
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Ventricular Extrasystoles
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Brain Oedema
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Carotid Artery Stenosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cerebrovascular Disorder
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    3 / 16 (18.75%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    3
    1
    Dizziness Postural
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Headache
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    2 / 16 (12.50%)
    2 / 6 (33.33%)
         occurrences all number
    1
    1
    2
    3
    Multiple Sclerosis Relapse
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Parkinsonism
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Syncope
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Seizure
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    5 / 16 (31.25%)
    2 / 6 (33.33%)
         occurrences all number
    0
    3
    11
    2
    Haemolysis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    3
    Haemolytic Anaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cold Type Haemolytic Anaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Increased Tendency To Bruise
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Leukopenia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Monoclonal B-Cell Lymphocytosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ear and labyrinth disorders
    Meniere's Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    2
    Tinnitus
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Dry Eye
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Macular Degeneration
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ocular Discomfort
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Photopsia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Visual Field Defect
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Visual Impairment
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal Distension
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Abdominal Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Abdominal Tenderness
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Abdominal Pain Upper
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    1
    3
    8
    Ascites
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    3 / 16 (18.75%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    3
    1
    Dental Caries
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 7 (14.29%)
    2 / 16 (12.50%)
    3 / 6 (50.00%)
         occurrences all number
    1
    1
    4
    4
    Dyspepsia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Dysphagia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    3
    0
    Gastritis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haemorrhoidal Haemorrhage
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastritis Erosive
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrooesophageal Reflux Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haemorrhoids
         subjects affected / exposed
    2 / 17 (11.76%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Oral Mucosal Blistering
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nausea
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    3 / 16 (18.75%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    3
    5
    Periodontal Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Stomatitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vomiting
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Hepatobiliary disorders
    Biliary Colic
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cholelithiasis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Drug Eruption
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Alopecia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Actinic Keratosis
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Nodular Vasculitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Hyperkeratosis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    1
    Panniculitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Eczema
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Rash Maculo-Papular
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Petechiae
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin Induration
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Skin Lesion
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    2 / 6 (33.33%)
         occurrences all number
    0
    0
    0
    2
    Skin Irritation
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Stasis Dermatitis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin Ulcer
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    0
    0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chronic Kidney Disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Dysuria
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haemoglobinuria
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Renal Failure
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Renal Impairment
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    2
    Arthralgia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    2
    3
    Coccydynia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Intervertebral Disc Calcification
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    3
    0
    Neck Pain
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Muscle Spasms
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Osteoporosis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pain In Extremity
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Rotator Cuff Syndrome
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Systemic Scleroderma
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Temporomandibular Joint Syndrome
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Tendonitis
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    0
    1
    Trigger Finger
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Infections and infestations
    Abdominal Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Bacteriuria
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bronchitis
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    0
    2
    Cystitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    7
    1
    Asymptomatic Covid-19
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Cystitis Bacterial
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Herpes Simplex Viraemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    2 / 17 (11.76%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    3
    0
    Fungal Skin Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Eye Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Escherichia Urinary Tract Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    2
    Infection
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 17 (11.76%)
    0 / 7 (0.00%)
    4 / 16 (25.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    6
    0
    Oral Herpes
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    1
    0
    Otitis Externa
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Otitis Externa Bacterial
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Rash Pustular
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Respiratory Tract Infection Viral
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Root Canal Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Skin Candida
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Skin Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Tinea Pedis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Tooth Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    2 / 17 (11.76%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    4
    0
    1
    2
    Urinary Tract Infection
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    3 / 16 (18.75%)
    2 / 6 (33.33%)
         occurrences all number
    1
    0
    13
    6
    Urinary Tract Infection Bacterial
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Viral Upper Respiratory Tract Infection
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Viral Infection
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 7 (14.29%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gout
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Decreased Appetite
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Iron Deficiency
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hyponatraemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    0 / 16 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    0
    1
    Magnesium Deficiency
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vitamin B12 Deficiency
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Malnutrition
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 7 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Feb 2018
    Following changes were done: • Changed urine pregnancy testing to serum or urine pregnancy testing beginning on Day 0. • Clarified that subjects who received a transfusion in Part A would not be withdrawn and would still be eligible to participate in Part B. • Excluded from Part B subjects who received prohibited medications in Part A. • Changed the collection of pharmacokinetic (PK), pharmacodynamic (PD), and antidrug antibody (ADA) samples from 6 to 9 weeks after the last dose of study drug in subjects who discontinue early and those who had a hematologic breakthrough event. • Changed inclusion criterion to “Ferritin above the lower limit of normal. Concurrent treatment with iron supplementation was permitted if the subject has been on a stable dose for the previous 4 weeks.” • Extended the requirement for highly effective contraception from 6 weeks following the last administration of study drug to 9 weeks. • Modified the exclusion criterion “Clinical diagnosis of systemic lupus erythematosus or other autoimmune disorders with antinuclear antibodies at Screening” to add that antinuclear antibodies of long-standing duration without associated clinical symptoms were to be adjudicated on a case-by-case basis. • Added total healthcare resource utilisation as an exploratory efficacy endpoint in Part A and as an efficacy endpoint in Part B. • Specified that vaccinations were to be administered in accordance with regional guidelines. • Added the occurrence of clinically significant hematologic breakthrough events attributable to the development of ADA and/or the development of positive SLE autoantibody titers as a criterion for the removal of a subject from study participation if, in the opinion of the Investigator, it could jeopardise the safety of the subject. • Clarified that subjects must be monitored for allergic reactions and anaphylaxis rather than infusion-related reactions. • Added solicited symptomatic anemia as a study assessment.
    09 Mar 2018
    Following changes were done: • Subjects requiring treatment with permitted concomitant medications and/or transfusions were not to be discontinued from the study. Subjects in Part B were transfused per the Transfusion Criteria. • Modified exclusion criterion “Clinical diagnosis of SLE or other autoimmune disorders with antinuclear antibodies at Screening” to add that antinuclear antibodies of longstanding duration without associated clinical symptoms were adjudicated on a case-by-case basis. • Extended the SFU visit for collection of AE data, PK, PD, and ADA samples from 6 weeks to 9 weeks after the last administration of study drug in subjects who discontinued early. • Increased the frequency of pregnancy testing (serum or urine). • Extended the recording period for AEs from 6 to 9 weeks after administration of the last dose of study drug. • Extended the reported period for SAEs from 6 to 9 weeks after the last dose of study drug or through the final study visit, whichever occurred later. • Increased the frequency of pregnancy testing (serum or urine).
    19 Dec 2019
    Following changes were done:• Added information regarding CAD. • Added an exploratory objective to evaluate the immunogenicity of sutimlimab and specified immunogenicity assessments evaluation, and conditions for ADA testing using available pre-dose PD back-up samples. • Added assessment in Part B of satisfaction with home infusion after first home infusion and after fourth home infusion. • Specified for subjects with home infusions, safety assessments were to include AEs with onset within 24 hours of infusion. • Added conditions for which subjects undergoing home infusions with study drug were to return to bi-weekly dosing, and which they may return to home infusions. • Specified collection of PK samples pre-dose and 1 hour(+-15 minutes) post-dose at 3-month intervals during the first year of treatment in Part B and then at 6-month intervals for the remainder of the time on study. • Specified collection of PD samples pre-dose and 1 hour(+-15 minutes) post-dose at 3-month intervals during the first year of treatment in Part B and then at 6-month intervals for the remainder of the time on study. • Increased the planned total study duration per subject to approximately 2.5 to 3.5 years. The duration of dosing in Part B was to last from 2 - 3 years. Part B was to run for 2 years following completion of LPO in Part A. Added SLE panel testing and ADA against sutimlimab for Part B Extension Phase. • Specified that immunisation review/vaccination was to be assessed during entire study. Revaccination with booster doses were to be given according to regional guidelines for subjects with persistent complement deficiency and in accordance with respective labels. • Added that in subjects who consented to the use of their blood samples for future research, PD back-up samples could be used to assay ADA. • Added that the hematology panel and clinical chemistry panel were to be performed every 2 weeks until Week 79 and then every 4 weeks after. •Removed "iron" from chemistry panel.

    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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