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    Clinical Trial Results:
    A Multicenter, Open-Label, Uncontrolled, Extension Study of RA101495 in Subjects with Paroxysmal Nocturnal Hemoglobinuria who have Completed a RA101495 Clinical Study

    Summary
    EudraCT number
    2016-003523-34
    Trial protocol
    FI   HU   DK   GB  
    Global end of trial date
    26 Oct 2021

    Results information
    Results version number
    v1
    This version publication date
    23 Sep 2022
    First version publication date
    23 Sep 2022
    Other versions
    v2

    Trial information

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    Trial identification
    Sponsor protocol code
    RA101495-01.202
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03225287
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    UCB Study Id: PNH001
    Sponsors
    Sponsor organisation name
    Ra Pharmaceuticals, Inc.
    Sponsor organisation address
    87 Cambridge Park Drive, Cambridge, Massachusetts, United States, 02140
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.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
    21 Oct 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Sep 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Oct 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    • To provide access to RA101495 for participants with PNH who have completed a Ra Pharmaceuticals sponsored study, have demonstrated clinical benefit, and who wish to continue receiving RA101495 for treatment of PNH • To evaluate the long-term safety and tolerability of RA101495 administered to participants with PNH who have completed a Ra Pharmaceuticals sponsored RA101495 clinical study • To evaluate the long-term preliminary efficacy of RA101495 administered to participants with PNH who have completed a Ra Pharmaceuticals sponsored RA101495 clinical study • To obtain periodic PK and PD data to confirm long-term maintenance of steady-state RA101495 plasma levels and sustained inhibition of hemolysis and complement
    Protection of trial subjects
    During the conduct of the study all participants were monitored for safety.
    Background therapy
    Background therapy as permitted in the protocol at the discretion of each treating physician.
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    17 Jul 2017
    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
    Australia: 3
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Finland: 1
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    Hungary: 2
    Country: Number of subjects enrolled
    New Zealand: 4
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    19
    EEA total number of subjects
    5
    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)
    13
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study started to enroll participants in July 2017 and concluded in October 2021.

    Pre-assignment
    Screening details
    The Participant Flow refers to the All Enrolled Subjects.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Zilucoplan-Cohort A (Eculizumab Naïve)
    Arm description
    Cohort A (Eculizumab Naive) included all participants from study RA101495-01.201 (NCT03078582) who had not received eculizumab for treatment of paroxysmal nocturnal hemoglobinuria (PNH). Participants received a loading dose of 0.3 milligram/kilogram (mg/kg) zilucoplan administered by subcutaneous (SC) injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Zilucoplan
    Investigational medicinal product code
    RA101495
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received zilucoplan administered by SC injection at pre-defined timepoints.

    Arm title
    Zilucoplan-Cohort B (Eculizumab Switch)
    Arm description
    Cohort B (Eculizumab Switch) included all participants from study RA101495-01.201 (NCT03078582) who had received eculizumab for treatment of PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Zilucoplan
    Investigational medicinal product code
    RA101495
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received zilucoplan administered by SC injection at pre-defined timepoints.

    Arm title
    Zilucoplan (Inadequate Responder to Eculizumab)
    Arm description
    Inadequate Responder cohort included participants from qualifying study RA101495-01.203 (NCT03030183) who had an inadequate response to eculizumab treatment for PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.
    Arm type
    Experimental

    Investigational medicinal product name
    Zilucoplan
    Investigational medicinal product code
    RA101495
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received zilucoplan administered by SC injection at pre-defined timepoints.

    Number of subjects in period 1
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Started
    10
    6
    3
    Completed
    0
    0
    0
    Not completed
    10
    6
    3
         Stem cell transplantation
    -
    1
    -
         Protocol non-compliance
    -
    -
    1
         Adverse event, non-fatal
    -
    -
    1
         Trial drug not effective
    -
    1
    -
         Sponsor, regulatory, or EC/IRB request
    7
    3
    1
         Subject withdraws consent
    3
    -
    -
         Need of transfusions and signs of hemolysis
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Zilucoplan-Cohort A (Eculizumab Naïve)
    Reporting group description
    Cohort A (Eculizumab Naive) included all participants from study RA101495-01.201 (NCT03078582) who had not received eculizumab for treatment of paroxysmal nocturnal hemoglobinuria (PNH). Participants received a loading dose of 0.3 milligram/kilogram (mg/kg) zilucoplan administered by subcutaneous (SC) injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Reporting group title
    Zilucoplan-Cohort B (Eculizumab Switch)
    Reporting group description
    Cohort B (Eculizumab Switch) included all participants from study RA101495-01.201 (NCT03078582) who had received eculizumab for treatment of PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Reporting group title
    Zilucoplan (Inadequate Responder to Eculizumab)
    Reporting group description
    Inadequate Responder cohort included participants from qualifying study RA101495-01.203 (NCT03030183) who had an inadequate response to eculizumab treatment for PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Reporting group values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab) Total
    Number of subjects
    10 6 3 19
    Age Categorical
    Units: participants
        <=18 years
    0 0 0 0
        Between 18 and 65 years
    6 4 3 13
        >=65 years
    4 2 0 6
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    59.6 ( 14.5 ) 45.0 ( 23.0 ) 35.3 ( 16.3 ) -
    Sex: Female, Male
    Units: participants
        Female
    6 1 1 8
        Male
    4 5 2 11

    End points

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    End points reporting groups
    Reporting group title
    Zilucoplan-Cohort A (Eculizumab Naïve)
    Reporting group description
    Cohort A (Eculizumab Naive) included all participants from study RA101495-01.201 (NCT03078582) who had not received eculizumab for treatment of paroxysmal nocturnal hemoglobinuria (PNH). Participants received a loading dose of 0.3 milligram/kilogram (mg/kg) zilucoplan administered by subcutaneous (SC) injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Reporting group title
    Zilucoplan-Cohort B (Eculizumab Switch)
    Reporting group description
    Cohort B (Eculizumab Switch) included all participants from study RA101495-01.201 (NCT03078582) who had received eculizumab for treatment of PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Reporting group title
    Zilucoplan (Inadequate Responder to Eculizumab)
    Reporting group description
    Inadequate Responder cohort included participants from qualifying study RA101495-01.203 (NCT03030183) who had an inadequate response to eculizumab treatment for PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Primary: Percentage of participants with Treatment Emergent Adverse events (TEAEs)

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    End point title
    Percentage of participants with Treatment Emergent Adverse events (TEAEs) [1]
    End point description
    TEAEs were defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study.
    End point type
    Primary
    End point timeframe
    From Day 1 until the Final Study Visit (up to Month 51)
    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: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    10
    6
    3
    Units: percentage of participants
        number (not applicable)
    90.0
    100
    66.7
    No statistical analyses for this end point

    Primary: Percentage of participants with Serious TEAEs

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    End point title
    Percentage of participants with Serious TEAEs [2]
    End point description
    Serious Adverse event (SAE) was defined as any untoward medical occurrence that:• results in death, • is life-threatening threatening (note that this refers to an event in which the participant was at risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe), • requires hospitalization or prolongation of existing hospitalization, • results in persistent or significant disability/incapacity, and • results in a congenital anomaly/birth defect. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study.
    End point type
    Primary
    End point timeframe
    From Day 1 until the Final Study Visit (up to Month 51)
    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: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    10
    6
    3
    Units: percentage of participants
        number (not applicable)
    10.0
    50.0
    66.7
    No statistical analyses for this end point

    Secondary: Number of participants with anti-drug antibodies (ADA)

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    End point title
    Number of participants with anti-drug antibodies (ADA)
    End point description
    Blood samples collection were planned to analyze for the presence/absence of ADAs to zilucoplan for immunogenicity assessments. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. The planned analysis of immunogenicity (ADA) was not performed as the assay was considered not fit for purpose due to an insufficient level of drug tolerance; therefore, no samples were processed.
    End point type
    Secondary
    End point timeframe
    At Day 1, Month 1, 2, 3, 6, 9, and 12
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    0 [3]
    0 [4]
    0 [5]
    Units: participants
    Notes
    [3] - Due to insufficient level of drug tolerance samples were not processed.
    [4] - Due to insufficient level of drug tolerance samples were not processed.
    [5] - Due to insufficient level of drug tolerance samples were not processed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Serum Lactate Dehydrogenase (LDH) Levels at each time point

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    End point title
    Change from Baseline in Serum Lactate Dehydrogenase (LDH) Levels at each time point
    End point description
    Serum LDH levels were measure of intravascular hemolysis. As high level of LDH in the blood was indicative of hemolysis in participants with PNH. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of this extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and Standard Deviation (SD) was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    3
    Units: Units per litre (U/L)
    arithmetic mean (standard deviation)
        Month 1 (n= 9, 6, 3)
    -3.7 ( 71.5 )
    10.0 ( 16.4 )
    336.7 ( 636.9 )
        Month 2 (n= 9, 5, 2)
    50.3 ( 156.2 )
    -2.4 ( 22.2 )
    676.5 ( 970.9 )
        Month 3 (n= 8, 5, 2)
    -6.5 ( 58.2 )
    -1.6 ( 40.5 )
    39.5 ( 40.3 )
        Month 6 (n=8, 5, 2)
    32.4 ( 142.5 )
    -28.4 ( 127.3 )
    -3.5 ( 12.0 )
        Month 9 (n=8, 3, 2 )
    -18.1 ( 59.7 )
    22.7 ( 23.6 )
    -5.0 ( 35.4 )
        Month 12 (n= 7, 3, 2)
    -39.7 ( 54.9 )
    8.7 ( 10.1 )
    456.0 ( 640.6 )
        Month 15 (n= 6, 3, 2)
    -24.5 ( 70.8 )
    4.0 ( 30.4 )
    174.5 ( 215.7 )
        Month 18 (n=7, 3, 1)
    -27.9 ( 54.8 )
    5.7 ( 56.8 )
    -56.0 ( 99999 )
        Month 21 (n= 7, 3, 1)
    -12.0 ( 93.9 )
    -7.3 ( 33.5 )
    73.0 ( 99999 )
        Month 24 (n= 7, 3, 1)
    -18.7 ( 53.9 )
    -27.0 ( 64.1 )
    -29.0 ( 99999 )
        Month 27 (n= 5, 2, 0)
    -14.0 ( 99.3 )
    58.0 ( 8.5 )
    99999 ( 99999 )
        Month 30 (n= 5, 2, 1)
    -28.0 ( 36.1 )
    59.0 ( 140.0 )
    1817.0 ( 99999 )
        Month 33 (n= 5, 3, 0)
    -39.0 ( 65.9 )
    -16.3 ( 66.7 )
    99999 ( 99999 )
        Month 36 (n= 5, 2, 0)
    -61.6 ( 47.1 )
    0.5 ( 4.9 )
    99999 ( 99999 )
        Month 39 (n= 5, 3, 0)
    -78.4 ( 80.9 )
    -29.7 ( 83.5 )
    99999 ( 99999 )
        Month 42 (n= 4, 2, 0)
    -42.3 ( 78.3 )
    35.5 ( 75.7 )
    99999 ( 99999 )
        Month 45 (n= 1, 1, 0)
    27.0 ( 99999 )
    53.0 ( 99999 )
    99999 ( 99999 )
        Final Study Visit (Month 51) (n= 9, 5, 2)
    41.6 ( 303.1 )
    -93.2 ( 139.8 )
    682.0 ( 548.7 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Total Bilirubin Values at each time point

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    End point title
    Change from Baseline in Total Bilirubin Values at each time point
    End point description
    Total Bilirubin was monitored for signs and symptoms of hepatic or biliary dysfunction. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of the extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and Standard Deviation (SD) was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    3
    Units: micromole per litre (umol/L)
    arithmetic mean (standard deviation)
        Month 1 (n= 9, 6, 3)
    -2.1 ( 7.7 )
    1.7 ( 6.2 )
    -0.3 ( 4.5 )
        Month 2 (n= 9, 5, 2)
    0.1 ( 10.7 )
    2.0 ( 7.2 )
    6.0 ( 2.8 )
        Month 3 (n= 8, 5, 2)
    1.4 ( 13.7 )
    8.2 ( 13.1 )
    3.5 ( 2.1 )
        Month 6 (n= 8, 5, 2)
    4.6 ( 14.8 )
    3.2 ( 7.2 )
    2.5 ( 0.7 )
        Month 9 (n= 8, 3, 2)
    -0.3 ( 7.4 )
    6.0 ( 3.0 )
    -1.0 ( 1.4 )
        Month 12 (n= 8, 3, 2)
    3.9 ( 8.4 )
    3.0 ( 2.0 )
    2.5 ( 3.5 )
        Month 15 (n= 7, 3, 2)
    -0.4 ( 6.4 )
    6.0 ( 9.5 )
    8.5 ( 9.2 )
        Month 18 (n= 6, 3, 1)
    2.8 ( 9.5 )
    2.0 ( 6.2 )
    3.0 ( 99999 )
        Month 21 (n= 7, 3, 1)
    3.9 ( 8.3 )
    2.0 ( 7.8 )
    7.0 ( 99999 )
        Month 24 (n= 7, 3, 1)
    5.1 ( 16.0 )
    -1.3 ( 3.1 )
    8.0 ( 99999 )
        Month 27 (n= 7, 2, 0)
    4.3 ( 12.2 )
    -2.0 ( 5.7 )
    99999 ( 99999 )
        Month 30 (n= 5, 2, 1)
    5.8 ( 14.6 )
    3.0 ( 7.1 )
    13.0 ( 99999 )
        Month 33 (n= 5, 3, 0)
    2.6 ( 5.7 )
    3.0 ( 2.6 )
    99999 ( 99999 )
        Month 36 (n= 5, 2, 0)
    -3.8 ( 6.8 )
    3.0 ( 0.0 )
    99999 ( 99999 )
        Month 39 (n= 5, 3, 0)
    0.2 ( 3.1 )
    0.7 ( 4.6 )
    99999 ( 99999 )
        Month 42 (n= 5, 2, 0)
    4.8 ( 15.5 )
    4.0 ( 15.6 )
    99999 ( 99999 )
        Month 45 (n= 2, 1, 0)
    5.0 ( 17.0 )
    -2.0 ( 99999 )
    99999 ( 99999 )
        Final Study Visit (Month 51) (n= 9, 5, 2)
    8.0 ( 17.3 )
    0.4 ( 3.9 )
    0.0 ( 9.9 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Total Hemoglobin Values at each time point

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    End point title
    Change from Baseline in Total Hemoglobin Values at each time point
    End point description
    Total Hemoglobin Values were analyzed for hematology assessments. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of the extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and Standard Deviation (SD) was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    3
    Units: grams per litre (g/L)
    arithmetic mean (standard deviation)
        Month 1 (n= 8, 6, 3)
    0.0 ( 11.4 )
    0.0 ( 8.2 )
    -5.7 ( 3.8 )
        Month 2 (n= 9, 5, 2)
    1.1 ( 8.3 )
    -5.0 ( 9.9 )
    -2.0 ( 11.3 )
        Month 3 (n= 7, 5, 2)
    6.4 ( 6.4 )
    3.0 ( 9.1 )
    -3.5 ( 6.4 )
        Month 6 (n= 8, 5, 2)
    1.1 ( 11.2 )
    2.0 ( 17.9 )
    -5.0 ( 17.0 )
        Month 9 (n= 8, 3, 2)
    2.9 ( 7.1 )
    -1.3 ( 4.0 )
    -9.0 ( 5.7 )
        Month 12 (n= 8, 3, 2)
    2.9 ( 6.1 )
    -1.7 ( 6.8 )
    -5.0 ( 17.0 )
        Month 15 (n= 7, 3, 2)
    3.9 ( 8.4 )
    -5.0 ( 5.3 )
    -9.0 ( 28.3 )
        Month 18 (n= 7, 3, 1)
    5.0 ( 4.9 )
    1.7 ( 9.5 )
    -2.0 ( 99999 )
        Month 21 (n= 7, 3, 1)
    6.4 ( 6.3 )
    -6.7 ( 7.6 )
    -1.0 ( 99999 )
        Month 24 (n= 7, 3, 0)
    7.9 ( 12.6 )
    -5.0 ( 2.6 )
    99999 ( 99999 )
        Month 27 (n= 7, 2, 0)
    7.0 ( 10.0 )
    -5.0 ( 11.3 )
    99999 ( 99999 )
        Month 30 (n= 5, 2, 1)
    10.8 ( 7.0 )
    -4.5 ( 12.0 )
    -8.0 ( 99999 )
        Month 33 (n= 5, 3, 0)
    10.0 ( 8.8 )
    -3.0 ( 4.4 )
    99999 ( 99999 )
        Month 36 (n= 5, 2, 0)
    8.4 ( 14.2 )
    -2.0 ( 4.2 )
    99999 ( 99999 )
        Month 39 (n= 5, 3, 0)
    7.6 ( 10.1 )
    4.7 ( 2.9 )
    99999 ( 99999 )
        Month 42 (n= 5, 2, 0)
    5.2 ( 11.2 )
    5.5 ( 0.7 )
    99999 ( 99999 )
        Month 45 (n= 3, 1, 0)
    -1.3 ( 23.3 )
    -4.0 ( 99999 )
    99999 ( 99999 )
        Final Study Visit (Month 51) (n= 9, 4, 1)
    1.8 ( 10.6 )
    -2.0 ( 4.1 )
    -7.0 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Free Hemoglobin Values at each time point

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    End point title
    Change from Baseline in Free Hemoglobin Values at each time point
    End point description
    Free Hemoglobin Values were analyzed for hematology assessments. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of the extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and Standard Deviation (SD) was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    7
    5
    2
    Units: milligrams per decilitre (mg/dL)
    arithmetic mean (standard deviation)
        Month 1 (n= 6, 5, 2)
    -0.20 ( 2.78 )
    2.86 ( 4.30 )
    0.80 ( 4.38 )
        Month 2 (n= 5, 5, 1)
    -1.14 ( 3.04 )
    0.48 ( 1.77 )
    6.10 ( 99999 )
        Month 3 (n= 5, 5, 1)
    1.34 ( 0.48 )
    -0.02 ( 0.95 )
    0.80 ( 99999 )
        Month 6 (n= 6, 4, 1)
    -0.43 ( 1.24 )
    0.55 ( 2.45 )
    1.20 ( 99999 )
        Month 9 (n= 6, 3, 1)
    -1.10 ( 2.11 )
    -1.50 ( 1.57 )
    0.00 ( 99999 )
        Month 12 (n= 7, 2, 1)
    -0.56 ( 2.80 )
    0.80 ( 0.28 )
    2.10 ( 99999 )
        Month 15 (n= 4, 2, 1)
    3.93 ( 11.61 )
    -1.35 ( 2.19 )
    1.60 ( 99999 )
        Month 18 (n= 4, 3, 0)
    1.98 ( 3.05 )
    0.77 ( 1.56 )
    99999 ( 99999 )
        Month 21 (n= 4, 2, 0)
    3.15 ( 5.84 )
    -1.30 ( 0.85 )
    99999 ( 99999 )
        Month 24 (n= 3, 2, 0)
    0.27 ( 0.35 )
    -0.50 ( 0.99 )
    99999 ( 99999 )
        Month 27 (n= 0, 0, 0)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Month 30 (n= 3, 0, 0)
    0.33 ( 2.37 )
    99999 ( 99999 )
    99999 ( 99999 )
        Month 33 (n= 3, 1, 0)
    0.17 ( 2.66 )
    5.80 ( 99999 )
    99999 ( 99999 )
        Month 36 (n= 0, 0, 0)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Month 39 (n= 1, 2, 0)
    -0.60 ( 99999 )
    -0.95 ( 0.64 )
    99999 ( 99999 )
        Month 42 (n= 1, 2, 0)
    1.30 ( 99999 )
    0.50 ( 3.68 )
    99999 ( 99999 )
        Month 45 (n= 0, 0, 0)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Final Study Visit (Month 51) (n= 1, 2, 1)
    -2.70 ( 99999 )
    -0.60 ( 1.13 )
    -3.10 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Haptoglobin Values at each time point

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    End point title
    Change from Baseline in Haptoglobin Values at each time point
    End point description
    Haptoglobin values were analyzed for hematology assessments. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of the extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and Standard Deviation (SD) was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    3
    Units: g/L
    arithmetic mean (standard deviation)
        Month 1 (n= 9, 6, 3)
    0.032 ( 0.097 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Month 2 (n= 9, 5, 2)
    0.053 ( 0.160 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Month 3 (n= 8, 5, 2)
    0.021 ( 0.060 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Month 6 (n= 8, 5, 2)
    0.031 ( 0.088 )
    0.036 ( 0.080 )
    0.020 ( 0.028 )
        Month 9 (n= 8, 3, 2)
    0.008 ( 0.021 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Month 12 (n= 8, 3, 2)
    0.000 ( 0.000 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Month 15 (n= 7, 3, 2)
    0.000 ( 0.000 )
    0.000 ( 0.000 )
    0.000 ( 0.000 )
        Month 18 (n= 7, 3, 1)
    0.000 ( 0.000 )
    0.000 ( 0.000 )
    0.000 ( 99999 )
        Month 21 (n= 7, 3, 1)
    0.030 ( 0.079 )
    0.000 ( 0.000 )
    0.000 ( 99999 )
        Month 24 (n= 7, 3, 1)
    0.030 ( 0.079 )
    0.000 ( 0.000 )
    0.000 ( 99999 )
        Month 27 (n= 7, 2, 0)
    0.000 ( 0.000 )
    0.000 ( 0.000 )
    99999 ( 99999 )
        Month 30 (n= 5, 2, 1)
    0.004 ( 0.009 )
    0.000 ( 0.000 )
    0.000 ( 99999 )
        Month 33 (n= 5, 3, 0)
    0.002 ( 0.004 )
    0.000 ( 0.000 )
    99999 ( 99999 )
        Month 36 (n= 5, 2, 0)
    0.036 ( 0.080 )
    0.000 ( 0.000 )
    99999 ( 99999 )
        Month 39 (n= 5, 3, 0)
    0.020 ( 0.045 )
    0.000 ( 0.000 )
    99999 ( 99999 )
        Month 42 (n= 5, 2, 0)
    0.034 ( 0.076 )
    0.000 ( 0.000 )
    99999 ( 99999 )
        Month 45 (n= 2, 1, 0)
    0.080 ( 0.113 )
    0.000 ( 99999 )
    99999 ( 99999 )
        Final Study Visit (Month 51) (n= 9, 5, 2)
    0.042 ( 0.127 )
    0.006 ( 0.013 )
    0.000 ( 0.000 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Reticulocytes Values at each time point

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    End point title
    Change from Baseline in Reticulocytes Values at each time point
    End point description
    Reticulocytes values were analyzed for hematology assessments. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of the extension study. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and Standard Deviation (SD) was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    3
    Units: 10^12 reticulocytes (cells)/L
    arithmetic mean (standard deviation)
        Month 1 (n= 8, 6, 3)
    0.0104 ( 0.0484 )
    0.0107 ( 0.0299 )
    -0.0457 ( 0.0505 )
        Month 2 (n= 9, 5, 2)
    -0.0046 ( 0.0354 )
    -0.0046 ( 0.0130 )
    0.0115 ( 0.0049 )
        Month 3 (n= 7, 5, 2)
    -0.0249 ( 0.0310 )
    -0.0112 ( 0.0251 )
    0.0170 ( 0.0113 )
        Month 6 (n= 8, 5, 2)
    -0.0006 ( 0.0452 )
    -0.0042 ( 0.0363 )
    0.0200 ( 0.0382 )
        Month 9 (n= 8, 3, 2)
    0.0063 ( 0.0334 )
    0.0070 ( 0.0171 )
    0.0640 ( 0.0297 )
        Month 12 (n= 8, 3, 2)
    -0.0041 ( 0.0427 )
    -0.0070 ( 0.0346 )
    0.0240 ( 0.0113 )
        Month 15 (n= 7, 3, 2)
    -0.0264 ( 0.0601 )
    -0.0343 ( 0.0191 )
    0.0285 ( 0.0290 )
        Month 18 (n= 7, 3, 1)
    -0.0040 ( 0.0382 )
    0.0027 ( 0.0380 )
    0.0460 ( 99999 )
        Month 21 (n= 7, 3, 0)
    -0.0223 ( 0.0554 )
    -0.0087 ( 0.0380 )
    99999 ( 99999 )
        Month 24 (n= 7, 3, 0)
    -0.0123 ( 0.0711 )
    -0.0093 ( 0.0186 )
    99999 ( 99999 )
        Month 27 (n= 7, 2, 0)
    -0.0017 ( 0.0553 )
    0.0150 ( 0.0127 )
    99999 ( 99999 )
        Month 30 (n= 5, 2, 1)
    0.0016 ( 0.0524 )
    0.0060 ( 0.0594 )
    0.0300 ( 99999 )
        Month 33 (n= 5, 3, 0)
    -0.0302 ( 0.0446 )
    -0.0093 ( 0.0234 )
    99999 ( 99999 )
        Month 36 (n= 5, 2, 0)
    -0.0630 ( 0.0621 )
    -0.0215 ( 0.0078 )
    99999 ( 99999 )
        Month 39 (n= 5, 3, 0)
    -0.0340 ( 0.0860 )
    -0.0133 ( 0.0291 )
    99999 ( 99999 )
        Month 42 (n= 5, 2, 0)
    -0.0270 ( 0.0721 )
    -0.0015 ( 0.0078 )
    99999 ( 99999 )
        Month 45 (n= 3, 1, 0)
    -0.0423 ( 0.1189 )
    -0.0050 ( 99999 )
    99999 ( 99999 )
        Final Study Visit (Month 51) (n= 8, 4, 1)
    -0.0433 ( 0.0480 )
    -0.0333 ( 0.0116 )
    0.0100 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hemoglobinuria Values at each time point

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    End point title
    Change from Baseline in Hemoglobinuria Values at each time point
    End point description
    Hemoglobinuria was assessed using a urine colorimetric scoring system with a score of 1 through 10 where 1 represents no hemoglobinuria and 10 represents maximum hemoglobinuria. Safety population included all participants who received at least 1 injection of zilucoplan on or after Day 1 of the extension study. Baseline was generally the final visit of the qualifying study (RA101495-01.201 or RA101495-01.203). Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' (Number analyzed) signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and Standard Deviation (SD) was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    3
    Units: score on a scale
    arithmetic mean (standard deviation)
        Month 1 (n= 8, 6, 3)
    0.1 ( 1.0 )
    0.2 ( 1.5 )
    1.7 ( 1.5 )
        Month 2 (n= 9, 5, 2)
    0.9 ( 1.4 )
    0.8 ( 1.3 )
    1.0 ( 1.4 )
        Month 3 (n= 8, 5, 1)
    0.4 ( 1.2 )
    0.8 ( 1.3 )
    0.0 ( 99999 )
        Month 6 (n= 8, 5, 1)
    0.4 ( 0.9 )
    0.8 ( 1.3 )
    0.0 ( 99999 )
        Month 9 (n= 8, 2, 1)
    0.4 ( 0.9 )
    1.5 ( 2.1 )
    0.0 ( 99999 )
        Month 12 (n= 8, 3, 2)
    0.9 ( 1.4 )
    1.0 ( 1.7 )
    1.0 ( 1.4 )
        Month 15 (n= 7, 3, 2)
    0.9 ( 1.1 )
    1.0 ( 1.7 )
    1.0 ( 1.4 )
        Month 18 (n= 7, 3, 1)
    0.1 ( 0.9 )
    0.3 ( 0.6 )
    0.0 ( 99999 )
        Month 21 (n= 7, 3, 1)
    0.7 ( 1.6 )
    1.0 ( 1.7 )
    0.0 ( 99999 )
        Month 24 (n= 7, 3, 1)
    0.6 ( 1.6 )
    0.3 ( 0.6 )
    0.0 ( 99999 )
        Month 27 (n= 7, 2, 1)
    0.7 ( 1.5 )
    1.5 ( 2.1 )
    0.0 ( 99999 )
        Month 30 (n= 5, 2, 1)
    0.6 ( 1.3 )
    1.5 ( 2.1 )
    0.0 ( 99999 )
        Month 33 (n= 5, 3, 0)
    1.4 ( 0.9 )
    1.0 ( 1.7 )
    99999 ( 99999 )
        Month 36 (n= 5, 2, 0)
    1.4 ( 1.9 )
    1.5 ( 2.1 )
    99999 ( 99999 )
        Month 39 (n= 5, 3, 0)
    0.4 ( 1.7 )
    1.0 ( 1.7 )
    99999 ( 99999 )
        Month 42 (n= 5, 2, 0)
    1.0 ( 1.2 )
    1.5 ( 2.1 )
    99999 ( 99999 )
        Month 45 (n= 3, 1, 0)
    1.0 ( 1.0 )
    -1.0 ( 99999 )
    99999 ( 99999 )
        Month 48 (n= 0, 0, 0)
    99999 ( 99999 )
    99999 ( 99999 )
    99999 ( 99999 )
        Final Study Visit (Month 51) (n= 9, 5, 2)
    0.4 ( 1.1 )
    0.6 ( 0.9 )
    2.5 ( 3.5 )
    No statistical analyses for this end point

    Secondary: Plasma concentrations of RA101495 and its major metabolite(s)

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    End point title
    Plasma concentrations of RA101495 and its major metabolite(s)
    End point description
    Blood samples of RA101495 (zilucoplan) and its metabolites (RA102758 and RA103488) were collected for Plasma concentration analysis. Pharmacokinetic (PK) population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. Here, 'n' signifies participants who were evaluable at specified time points. ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    At Day 1 (Screening), Month 1, 2, 3, 6, 9, 12, and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    3
    Units: micrograms per litre (ug/L)
    arithmetic mean (standard deviation)
        RA101495- Day 1 (n= 9, 5, 3)
    10999.99 ( 2698.29 )
    13616.08 ( 1490.81 )
    6976.50 ( 5663.23 )
        RA101495- Month 1 (n= 9, 6, 3)
    10879.13 ( 2405.19 )
    12645.38 ( 1620.31 )
    7630.03 ( 7060.56 )
        RA101495- Month 2 (n= 9, 5, 2)
    11276.17 ( 2896.98 )
    12220.10 ( 2188.78 )
    6865.45 ( 8108.18 )
        RA101495- Month 3 (n= 8, 5, 2)
    10806.17 ( 3418.92 )
    12315.28 ( 2515.84 )
    12430.00 ( 16.55 )
        RA101495- Month 6 (n= 6, 5, 1)
    9393.42 ( 2224.52 )
    12218.72 ( 2166.05 )
    12254.00 ( 99999 )
        RA101495- Month 9 (n= 7, 3, 2)
    11848.67 ( 2685.92 )
    12282.83 ( 3064.42 )
    15193.35 ( 2756.66 )
        RA101495- Month 12 (n= 8, 3, 2)
    11495.99 ( 2885.81 )
    13279.97 ( 2148.60 )
    12038.65 ( 7934.94 )
        RA101495-Final Study Visit (Month 51) (n= 0, 0, 1)
    99999 ( 99999 )
    99999 ( 99999 )
    7174.20 ( 99999 )
        RA102758- Day 1 (n= 9, 5, 3)
    1883.49 ( 593.93 )
    2443.62 ( 560.97 )
    1280.07 ( 1109.03 )
        RA102758- Month 1 (n= 9, 6, 3)
    1865.06 ( 594.31 )
    2185.00 ( 631.37 )
    757.30 ( 997.44 )
        RA102758- Month 2 (n= 9, 5, 2)
    1894.86 ( 608.46 )
    2090.04 ( 831.80 )
    757.85 ( 1018.59 )
        RA102758- Month 3 (n= 8, 5, 2)
    1758.55 ( 689.03 )
    1990.54 ( 700.70 )
    1954.05 ( 160.58 )
        RA102758- Month 6 (n= 6, 5, 1)
    1467.85 ( 563.68 )
    1819.20 ( 613.14 )
    1725.50 ( 99999 )
        RA102758- Month 9 (n= 7, 3, 2)
    1686.80 ( 554.87 )
    1881.73 ( 583.87 )
    1238.55 ( 166.24 )
        RA102758- Month 12 (n= 8, 3, 1)
    1646.99 ( 536.00 )
    1954.23 ( 725.54 )
    10.00 ( 99999 )
        RA102758- Final Study Visit (Month 51) (n=0,0,1)
    99999 ( 99999 )
    99999 ( 99999 )
    1094.60 ( 99999 )
        RA103488- Day 1 (n= 9, 5, 3)
    3587.68 ( 1747.12 )
    4887.98 ( 1969.22 )
    2084.83 ( 1791.35 )
        RA103488- Month 1 (n= 9, 6, 3)
    4344.99 ( 2319.10 )
    4400.68 ( 1823.93 )
    1703.73 ( 1605.96 )
        RA103488- Month 2 (n= 9, 5, 2)
    4799.29 ( 3113.57 )
    4365.84 ( 1537.67 )
    1591.35 ( 1552.03 )
        RA103488- Month 3 (n= 8, 5, 2)
    4191.36 ( 2347.65 )
    4541.78 ( 1706.07 )
    2715.60 ( 1345.48 )
        RA103488- Month 6 (n= 6, 5, 1)
    4027.53 ( 2730.92 )
    4436.46 ( 2341.16 )
    1929.60 ( 99999 )
        RA103488- Month 9 (n= 7, 3, 2)
    3132.54 ( 1320.61 )
    4217.97 ( 2015.36 )
    2954.85 ( 1754.97 )
        RA103488- Month 12 (n= 8, 3, 2)
    3903.41 ( 1960.30 )
    4334.47 ( 1976.47 )
    2319.20 ( 2534.84 )
        RA103488- Final Study Visit (Month 51) (n=0,0,1)
    99999 ( 99999 )
    99999 ( 99999 )
    2210.00 ( 99999 )
    No statistical analyses for this end point

    Secondary: Maximum plasma concentration (Cmax) of RA101495

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    End point title
    Maximum plasma concentration (Cmax) of RA101495
    End point description
    Cmax is the maximum plasma drug concentration. PK population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. Data was not collected and analyzed for this outcome measure due to change in planned analysis.
    End point type
    Secondary
    End point timeframe
    At Day 1, Month 1, 2, 3, 6, 9, and 12
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    0 [6]
    0 [7]
    0 [8]
    Units: ug/L
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    Notes
    [6] - As per the change in planned analyses, maximum plasma concentration was not collected and analyzed.
    [7] - As per the change in planned analyses, maximum plasma concentration was not collected and analyzed.
    [8] - As per the change in planned analyses, maximum plasma concentration was not collected and analyzed.
    No statistical analyses for this end point

    Secondary: Time corresponding to Cmax (tmax) of RA101495

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    End point title
    Time corresponding to Cmax (tmax) of RA101495
    End point description
    tmax is the time to corresponding Cmax. PK population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. Data was not collected and analyzed for this outcome measure due to change in planned analysis.
    End point type
    Secondary
    End point timeframe
    At Day 1, Month 1, 2, 3, 6, 9, and 12
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    0 [9]
    0 [10]
    0 [11]
    Units: hours (h)
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    Notes
    [9] - As per the change in planned analyses, time corresponding to Cmax was not collected and analyzed.
    [10] - As per the change in planned analyses, time corresponding to Cmax was not collected and analyzed.
    [11] - As per the change in planned analyses, time corresponding to Cmax was not collected and analyzed.
    No statistical analyses for this end point

    Secondary: Area under the drug concentration-time curve (AUC0-t) of RA101495

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    End point title
    Area under the drug concentration-time curve (AUC0-t) of RA101495
    End point description
    AUC0-t is area under the drug concentration-time curves. PK population included all participants in the Safety population who had at least 1 plasma sample obtained for PK assessment. As per the change in planned analyses, samples/data were not collected, and AUC0-t not calculated.
    End point type
    Secondary
    End point timeframe
    At Day 1, Month 1, 2, 3, 6, 9, and 12
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    0 [12]
    0 [13]
    0 [14]
    Units: hours*ug/L
        geometric mean (geometric coefficient of variation)
    ( )
    ( )
    ( )
    Notes
    [12] - As per the change in planned analyses, samples/data were not collected, and AUC0-t not calculated.
    [13] - As per the change in planned analyses, samples/data were not collected, and AUC0-t not calculated.
    [14] - As per the change in planned analyses, samples/data were not collected, and AUC0-t not calculated.
    No statistical analyses for this end point

    Secondary: Total complement (CH50) Levels

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    End point title
    Total complement (CH50) Levels
    End point description
    Blood samples collection were planned to assess complement (CH50) levels. The planned analysis of CH50 was not performed because the CH50 assay was not able to be validated due to lack of reproducibility of the manufacturer’s kits. Pharmacodynamic (PD) population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Data was not collected and analyzed for this outcome measure due to change in planned analysis.
    End point type
    Secondary
    End point timeframe
    At Day 1, Month 1, 2, 3, 6, 9, and 12
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    0 [15]
    0 [16]
    0 [17]
    Units: ug/mL
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [15] - As per the change in planned analyses, CH50 levels were not collected and analyzed.
    [16] - As per the change in planned analyses, CH50 levels were not collected and analyzed.
    [17] - As per the change in planned analyses, CH50 levels were not collected and analyzed.
    No statistical analyses for this end point

    Secondary: Change from Baseline in Sheep Red Blood Cell (sRBC) Values at each time point

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    End point title
    Change from Baseline in Sheep Red Blood Cell (sRBC) Values at each time point
    End point description
    Blood samples were collected for measurement of sRBC lysis for the Classical Complement Pathways. PD population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and SD was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    1
    Units: percent lysis of sheep erythrocytes
    arithmetic mean (standard deviation)
        Month 1 (n= 9, 6,1)
    1.378 ( 2.277 )
    0.523 ( 0.772 )
    93.870 ( 99999 )
        Month 2 (n= 9, 5,1)
    1.248 ( 1.789 )
    -0.308 ( 0.452 )
    93.870 ( 99999 )
        Month 3 (n= 8, 5, 1)
    1.256 ( 1.799 )
    0.576 ( 0.972 )
    -2.620 ( 99999 )
        Month 6 (n= 6, 5, 1)
    1.493 ( 2.838 )
    0.458 ( 1.657 )
    -2.300 ( 99999 )
        Month 9 (n= 7, 3, 1)
    0.683 ( 1.055 )
    0.757 ( 0.673 )
    -1.410 ( 99999 )
        Month 12 (n= 8, 3, 1)
    0.759 ( 0.557 )
    0.773 ( 0.415 )
    8.390 ( 99999 )
        Final Study Visit (Month 51) (n= 0, 2, 0)
    99999 ( 99999 )
    25.230 ( 35.200 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Wieslab enzyme-linked immunosorbent assay (ELISA) Values for alternative complement pathway at each time point

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    End point title
    Change from Baseline in Wieslab enzyme-linked immunosorbent assay (ELISA) Values for alternative complement pathway at each time point
    End point description
    Blood samples were collected for measurement of membrane attack complex (MAC) by Wieslab ELISA for alternative complement pathway. PD population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and SD was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    2
    Units: percentage of activity
    arithmetic mean (standard deviation)
        Month 1 (n= 9, 6, 2)
    1.7 ( 5.8 )
    1.0 ( 1.7 )
    48.0 ( 67.9 )
        Month 2 (n= 9, 5, 2)
    0.1 ( 1.9 )
    -1.0 ( 1.0 )
    51.5 ( 74.2 )
        Month 3 (n= 8, 5, 2)
    0.1 ( 2.0 )
    0.0 ( 0.7 )
    2.0 ( 1.4 )
        Month 6 (n= 6, 5, 1)
    1.0 ( 4.5 )
    -0.2 ( 1.9 )
    5.0 ( 99999 )
        Month 9 (n= 8, 3, 1)
    -0.9 ( 0.8 )
    -0.7 ( 0.6 )
    -2.0 ( 99999 )
        Month 12 (n= 8, 3, 2)
    -1.4 ( 1.4 )
    -1.3 ( 0.6 )
    4.5 ( 6.4 )
        Final Study Visit (Month 51) (n= 0, 2, 0)
    99999 ( 99999 )
    1.0 ( 2.8 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Complement Component 5 (C5) Values at each time point

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    End point title
    Change from Baseline in Complement Component 5 (C5) Values at each time point
    End point description
    Blood samples were collected for measurement of Complement component 5 (C5) levels. PD population included all participants in the Safety population who had at least 1 plasma sample obtained for PD assessment. Here, Number of participants analyzed included those participants who were evaluable for the assessment and 'n' signifies participants who were evaluable at specified time points. '99999' (n=0) signifies that the Mean and SD was not calculated due to 0 participants and ‘99999’ (n=1) signifies that SD could not be calculated for a single participant.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 1, 2, 3, 6, 9, 12 and Final Study Visit (Month 51)
    End point values
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan-Cohort B (Eculizumab Switch) Zilucoplan (Inadequate Responder to Eculizumab)
    Number of subjects analysed
    9
    6
    2
    Units: ug/mL
    arithmetic mean (standard deviation)
        Month 1 (n= 9, 6, 2)
    -11.231 ( 24.960 )
    20.488 ( 31.024 )
    -27.505 ( 90.092 )
        Month 2 (n= 9, 5, 2)
    -15.914 ( 32.737 )
    17.716 ( 33.125 )
    16.310 ( 36.077 )
        Month 3 (n= 8, 5, 2)
    -24.404 ( 50.084 )
    -2.898 ( 49.747 )
    22.355 ( 19.764 )
        Month 6 (n= 6, 5, 1)
    -6.823 ( 44.787 )
    9.572 ( 24.927 )
    91.640 ( 99999 )
        Month 9 (n= 8, 3, 1)
    -0.019 ( 53.475 )
    1.177 ( 27.654 )
    89.670 ( 99999 )
        Month 12 (n= 7, 3, 2)
    -40.591 ( 34.977 )
    -23.487 ( 30.911 )
    -24.905 ( 17.685 )
        Final Study Visit (Month 51) (n= 3, 3, 0)
    -28.663 ( 46.526 )
    -19.770 ( 74.604 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 until the Final Study Visit (up to Month 51)
    Adverse event reporting additional description
    TEAEs defined as an AE that occurs after a participant's initial treatment zilucoplan start for this study (RA101495-01.202) that was not present at the time of treatment start, or an AE that increases in severity after treatment start in this study, if the event was present at the time of treatment start. TEAEs were reported for Safety population.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    Zilucoplan-Cohort A (Eculizumab Naïve)
    Reporting group description
    Cohort A (Eculizumab Naive) included all participants from study RA101495-01.201 (NCT03078582) who had not received eculizumab for treatment of paroxysmal nocturnal hemoglobinuria (PNH). Participants received a loading dose of 0.3 milligram/kilogram (mg/kg) zilucoplan administered by subcutaneous (SC) injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Reporting group title
    Zilucoplan (Inadequate Responder to Eculizumab)
    Reporting group description
    Inadequate Responder cohort included participants from qualifying study RA101495-01.203 (NCT03030183) who had an inadequate response to eculizumab treatment for PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Reporting group title
    Zilucoplan-Cohort B (Eculizumab Switch)
    Reporting group description
    Cohort B (Eculizumab Switch) included all participants from study RA101495-01.201 (NCT03078582) who had received eculizumab for treatment of PNH. Participants received a loading dose of 0.3 mg/kg zilucoplan administered by SC injection at Day 1 of this study. Following in-clinic education and training, all participants self-injected 0.1 mg/kg of zilucoplan by SC injection once daily for 12 months. From Week 2 onwards, if a participant had not achieved an adequate response, the zilucoplan dose was escalated to 0.3 mg/kg daily.

    Serious adverse events
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan (Inadequate Responder to Eculizumab) Zilucoplan-Cohort B (Eculizumab Switch)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 3 (66.67%)
    3 / 6 (50.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Encephalopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tongue haematoma
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Enterocolitis infectious
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Zilucoplan-Cohort A (Eculizumab Naïve) Zilucoplan (Inadequate Responder to Eculizumab) Zilucoplan-Cohort B (Eculizumab Switch)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 10 (90.00%)
    2 / 3 (66.67%)
    6 / 6 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Lymphoedema
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 10 (40.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
         occurrences all number
    9
    1
    3
    Chest discomfort
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Pyrexia
         subjects affected / exposed
    3 / 10 (30.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    Injection site bruising
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    1
    Chest pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Injection site haematoma
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Chills
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    Alloimmunisation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    3 / 10 (30.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    0
    Dyspnoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Cough
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    2
    1
    0
    Laryngospasm
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Pleural effusion
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    1
    Insomnia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Grip strength decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    Post vaccination syndrome
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Animal bite
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Bone contusion
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Eye contusion
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Fall
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Foot fracture
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Limb injury
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Post-traumatic pain
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Tooth fracture
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Traumatic haematoma
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 3 (33.33%)
    2 / 6 (33.33%)
         occurrences all number
    4
    2
    6
    Dizziness
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    0
    Amnesia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Sensory disturbance
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    0
    Aplastic anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    2
    Haemolysis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    Pancytopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    5 / 10 (50.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    8
    0
    1
    Nausea
         subjects affected / exposed
    4 / 10 (40.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    5
    0
    0
    Abdominal pain
         subjects affected / exposed
    3 / 10 (30.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    7
    0
    0
    Constipation
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    Abdominal distension
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Abdominal discomfort
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Large intestine polyp
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Oral discomfort
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Oral pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Rectal polyp
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Vomiting
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Retching
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Actinic keratosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Psoriasis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Rash
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Rash pruritic
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Urticaria
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Renal and urinary disorders
    Chromaturia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Paroxysmal nocturnal haemoglobinuria
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    3
    0
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 10 (30.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    9
    1
    0
    Muscle spasms
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    6
    0
    0
    Arthralgia
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    Myalgia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    Pain in extremity
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Arthritis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Limb discomfort
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Joint swelling
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Muscle tightness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Plantar fasciitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 10 (40.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    10
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 10 (40.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    5
    0
    1
    Viral infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    Sinusitis
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    0
    Pharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    1
    Bronchitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Influenza
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Rhinitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    0
    Cystitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Ear infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Hordeolum
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Oral herpes
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Skin bacterial infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Skin infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Tooth abscess
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 3 (0.00%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 3 (33.33%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 3 (0.00%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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