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    Clinical Trial Results:
    A Randomized, Double-blind, Active-controlled, Phase 3 Study Evaluating the Efficacy and Safety of ABP 959 Compared With Eculizumab in Adult Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)

    Summary
    EudraCT number
    2017-001418-27
    Trial protocol
    DE   ES   NL   GB   CZ   NO   SI   IE   FI   SE   PT   IT  
    Global end of trial date
    12 Jul 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Apr 2023
    First version publication date
    13 Apr 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20150168
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03818607
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States,
    Public contact
    Study Director, Amgen Inc., medinfo@amgen.com
    Scientific contact
    Study Director, Amgen Inc., medinfo@amgen.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
    12 Jul 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Jul 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study was to evaluate the efficacy of ABP 959 compared with that of eculizumab based on control of intravascular hemolysis.
    Protection of trial subjects
    The study was conducted in accordance with the Note for Guidance on Good Clinical Practice (International Council for Harmonisation Guideline E6 [R1] and 21 Code of Federal Regulations Parts 50, 56, and 312), the general principles indicated in the Declaration of Helsinki, and all applicable regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    22 Jan 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Turkey: 3
    Country: Number of subjects enrolled
    Finland: 2
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    Norway: 2
    Country: Number of subjects enrolled
    Portugal: 2
    Country: Number of subjects enrolled
    Slovenia: 2
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    France: 1
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    United States: 1
    Worldwide total number of subjects
    42
    EEA total number of subjects
    32
    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)
    30
    From 65 to 84 years
    12
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Participants were enrolled at 25 research centers in 14 countries including the Czech Republic, Finland, France, Ireland, Italy, the Netherlands, Norway, Portugal, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and the United States, and participated from 22 January 2019 to 12 July 2022

    Pre-assignment
    Screening details
    42 adult participants with PNH were enrolled and randomized in a 1:1 ratio to receive each investigational product (ABP 959 and eculizumab) in 1 of 2 treatment sequences. Randomization was stratified by red blood cell (RBC) transfusion received within the last 12 months before randomization. There was no washout between Periods 1 and 2.

    Period 1
    Period 1 title
    Period 1 (Week 1 to Week 52)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    ABP 959/Eculizumab
    Arm description
    Participants received ABP 959 900 mg administered intravenously (IV) every 14 ± 2 days for 52 weeks in Period 1 followed by eculizumab 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.
    Arm type
    Experimental

    Investigational medicinal product name
    ABP 959
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ABP 959 900 mg was administered IV every 14 ± 2 days for 52 weeks in Period 1.

    Arm title
    Eculizumab/ABP 959
    Arm description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1 followed by ABP 959 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.
    Arm type
    Active comparator

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eculizumab 900 mg was administered IV every 14 ± 2 days for 52 weeks in Period 1.

    Number of subjects in period 1
    ABP 959/Eculizumab Eculizumab/ABP 959
    Started
    20
    22
    Participants treated
    20
    22
    Completed
    20
    21
    Not completed
    0
    1
         Adverse event, non-fatal
    -
    1
    Period 2
    Period 2 title
    Period 2 (Week 53 to Week 79)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    ABP 959/Eculizumab
    Arm description
    Participants received ABP 959 900 mg administered intravenously (IV) every 14 ± 2 days for 52 weeks in Period 1 followed by eculizumab 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.
    Arm type
    Active comparator

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eculizumab 900 mg was administered IV every 14 ± 2 days for 26 weeks in Period 2

    Arm title
    Eculizumab/ABP 959
    Arm description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1 followed by ABP 959 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.
    Arm type
    Experimental

    Investigational medicinal product name
    ABP 959
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    ABP 959 900 mg was administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Number of subjects in period 2
    ABP 959/Eculizumab Eculizumab/ABP 959
    Started
    20
    21
    Participants treated
    20
    21
    Completed
    19
    20
    Not completed
    1
    1
         Consent withdrawn by subject
    1
    -
         Participant's personal needs
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    ABP 959/Eculizumab
    Reporting group description
    Participants received ABP 959 900 mg administered intravenously (IV) every 14 ± 2 days for 52 weeks in Period 1 followed by eculizumab 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Reporting group title
    Eculizumab/ABP 959
    Reporting group description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1 followed by ABP 959 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Reporting group values
    ABP 959/Eculizumab Eculizumab/ABP 959 Total
    Number of subjects
    20 22 42
    Age categorical
    Units: Subjects
        In Utero
    0 0 0
        Pre-term newborn - gestational age < 37 wk
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    15 15 30
        Elderly (From 65-84 years)
    5 7 12
        Elderly 85 years and over
    0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    50.2 ( 16.73 ) 50.2 ( 16.90 ) -
    Sex: Female, Male
    Units: Participants
        Female
    11 11 22
        Male
    9 11 20
    Race/Ethnicity, Customized
    Units: Subjects
        White
    16 17 33
        Asian
    0 1 1
        Not allowed to collect
    4 4 8
    RBC Transfusion Within 12 Months Before Randomization per Electronic Case Report Form (eCRF)
    Units: Subjects
        Yes
    2 3 5
        No
    18 19 37
    Mean Number of Packed RBC Units Received in Last 12 Months
    Number of units of packed RBCs that were transfused in the 12 months prior to enrollment.
    Units: Packed RBC Units
        arithmetic mean (standard deviation)
    1.5 ( 0.71 ) 1.7 ( 1.15 ) -

    End points

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    End points reporting groups
    Reporting group title
    ABP 959/Eculizumab
    Reporting group description
    Participants received ABP 959 900 mg administered intravenously (IV) every 14 ± 2 days for 52 weeks in Period 1 followed by eculizumab 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Reporting group title
    Eculizumab/ABP 959
    Reporting group description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1 followed by ABP 959 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.
    Reporting group title
    ABP 959/Eculizumab
    Reporting group description
    Participants received ABP 959 900 mg administered intravenously (IV) every 14 ± 2 days for 52 weeks in Period 1 followed by eculizumab 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Reporting group title
    Eculizumab/ABP 959
    Reporting group description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1 followed by ABP 959 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Subject analysis set title
    ABP 959
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants in the modified FAS who received ABP 959 900 mg in Period 1 (administered IV every 14 ± 2 days for 52 weeks) or ABP 959 900 mg in Period 2 (administered IV every 14 ± 2 days for 26 weeks).

    Subject analysis set title
    Eculizumab
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants in the modified FAS who received eculizumab 900 mg in Period 1 (administered IV every 14 ± 2 days for 52 weeks) or eculizumab 900 mg in Period 2 (administered IV every 14 ± 2 days for 26 weeks).

    Subject analysis set title
    ABP 959
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants who received ABP 959 900 mg in Period 1 (administered IV every 14 ± 2 days for 52 weeks) or ABP 900 mg in Period 2 (administered IV every 14 ± 2 days for 26 weeks).

    Subject analysis set title
    Eculizumab
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants who received eculizumab 900 mg in Period 1 (administered IV every 14 ± 2 days for 52 weeks) or eculizumab 900 mg in Period 2 (administered IV every 14 ± 2 days for 26 weeks).

    Subject analysis set title
    ABP 959
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received ABP 959 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1.

    Subject analysis set title
    Eculizumab
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1.

    Subject analysis set title
    ABP 959
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants who received ABP 959 900 mg in Period 1 (administered IV every 14 ± 2 days for 52 weeks) or ABP 959 900 mg in Period 2 (administered IV every 14 ± 2 days for 26 weeks).

    Subject analysis set title
    Eculizumab
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants who received eculizumab 900 mg in Period 1 (administered IV every 14 ± 2 days for 52 weeks) or eculizumab 900 mg in Period 2 (administered IV every 14 ± 2 days for 26 weeks).

    Subject analysis set title
    ABP 959/Eculizumab
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received ABP 959 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1 followed by eculizumab 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Subject analysis set title
    Eculizumab/ABP 959
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1 followed by ABP 959 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Primary: LDH Level at Week 27 (Parallel Comparison)

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    End point title
    LDH Level at Week 27 (Parallel Comparison)
    End point description
    The primary analysis for the parallel comparison was hemolysis as measured by LDH at Week 27 by initial treatment received (Period 1). The full analysis set (FAS) included all randomized participants.
    End point type
    Primary
    End point timeframe
    Week 27
    End point values
    ABP 959 Eculizumab
    Number of subjects analysed
    20
    22
    Units: U/L
        least squares mean (confidence interval 95%)
    205.69 (191.23 to 221.24)
    193.53 (180.80 to 207.17)
    Statistical analysis title
    Ratio of Week 27 LDH levels (ABP959/eculizumab)
    Comparison groups
    ABP 959 v Eculizumab
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    Method
    Parameter type
    Geometric LS mean ratio (GMR)
    Point estimate
    1.0628
    Confidence interval
         level
    97.5%
         sides
    1-sided
         lower limit
    -
         upper limit
    1.1576
    Notes
    [1] - The clinical similarity of the Week 27 LDH between treatments was assessed by comparing the 1-sided 97.5% upper confidence interval (CI) limit for the geometric mean ratio of LDH at Week 27 between ABP 959 treatment and eculizumab treatment with a non-inferiority margin of 2.873.

    Primary: Time-adjusted Area Under the Effect Curve (AUEC) of LDH (Crossover Comparison)

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    End point title
    Time-adjusted Area Under the Effect Curve (AUEC) of LDH (Crossover Comparison)
    End point description
    The primary analysis for the crossover comparison was hemolysis, as measured by the time-adjusted AUEC of LDH, according to treatment per randomized sequence regardless of treatment actually received. The modified FAS included all randomized participants with an LDH-time profile evaluable for the time-adjusted AUEC, according to treatment per the randomized sequence regardless of treatment actually received.
    End point type
    Primary
    End point timeframe
    From Week 13 to Week 27, from Week 39 to Week 53, and from Week 65 to Week 79
    End point values
    ABP 959 Eculizumab
    Number of subjects analysed
    40
    40
    Units: U*day/L/week
        least squares mean (confidence interval 95%)
    1445.76 (1295.63 to 1613.28)
    1473.44 (1321.86 to 1642.41)
    Statistical analysis title
    Ratio of LDH levels (ABP 959/eculizumab)
    Comparison groups
    ABP 959 v Eculizumab
    Number of subjects included in analysis
    80
    Analysis specification
    Pre-specified
    Analysis type
    other [2]
    Method
    Parameter type
    GMR
    Point estimate
    0.9812
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.9403
         upper limit
    1.0239
    Notes
    [2] - The clinical similarity of the AUEC between treatments was assessed by comparing 2-sided 90% CI for the GMR of the time-adjusted AUEC of LDH (Week 13 to Week 27, Week 39 to Week 53, and Week 65 to Week 79) between ABP 959 treatment and eculizumab treatment with a similarity margin of (0.77, 1.30).

    Secondary: Mean Total Complement (50% Total Hemolytic Complement Activity [CH50])

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    End point title
    Mean Total Complement (50% Total Hemolytic Complement Activity [CH50])
    End point description
    Total complement (%) was measured in serum using an assay method and compared the total hemolytic complement activity to the lower limit of the normal human reference (LLN) of 58 U/mL for all CH50 values. The percent of LLN of CH50 at each time point was calculated as mean CH50 results/LLN x 100%. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: Percent of LLN for all CH50 values
    arithmetic mean (standard deviation)
        Baseline (N = 20; 22)
    6.4 ( 13.48 )
    2.6 ( 4.11 )
        Week 27 (N = 19; 21)
    7.5 ( 16.68 )
    6.3 ( 12.25 )
        Week 39 (N = 17; 21)
    7.4 ( 23.80 )
    5.1 ( 10.36 )
        Week 53 (N = 20; 21)
    12.0 ( 34.29 )
    4.6 ( 6.84 )
        Week 65 (N = 16; 18)
    25.6 ( 65.27 )
    7.8 ( 11.37 )
        Week 79 (N = 18; 20)
    15.8 ( 35.65 )
    6.5 ( 12.67 )
    No statistical analyses for this end point

    Secondary: Mean Total Hemoglobin Levels

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    End point title
    Mean Total Hemoglobin Levels
    End point description
    Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: g/L
    arithmetic mean (standard deviation)
        Baseline (N = 20; 21)
    113.0 ( 15.03 )
    113.8 ( 16.09 )
        Week 27 (N = 18; 20)
    110.6 ( 15.19 )
    116.1 ( 16.08 )
        Week 39 (N = 16; 20)
    114.6 ( 14.12 )
    115.0 ( 15.39 )
        Week 53 (N = 19; 21)
    109.8 ( 15.17 )
    115.8 ( 15.20 )
        Week 65 (N = 15; 18)
    106.9 ( 17.74 )
    115.7 ( 18.36 )
        Week 79 (N = 19; 20)
    113.0 ( 16.78 )
    115.7 ( 16.75 )
    No statistical analyses for this end point

    Secondary: Mean Serum-free Hemoglobin Levels

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    End point title
    Mean Serum-free Hemoglobin Levels
    End point description
    Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: mg/dL
    arithmetic mean (standard deviation)
        Baseline (N = 20; 22)
    9.30 ( 26.960 )
    3.76 ( 2.758 )
        Week 27 (N = 17; 21)
    5.38 ( 14.839 )
    3.10 ( 2.920 )
        Week 39 (N = 17; 21)
    3.74 ( 5.093 )
    10.25 ( 27.926 )
        Week 53 (N = 18; 21)
    13.60 ( 33.793 )
    3.08 ( 2.529 )
        Week 65 (N = 16; 18)
    3.22 ( 2.249 )
    2.75 ( 2.077 )
        Week 79 (N = 17; 15)
    6.59 ( 10.232 )
    13.89 ( 41.634 )
    No statistical analyses for this end point

    Secondary: Mean Haptoglobin Levels

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    End point title
    Mean Haptoglobin Levels
    End point description
    Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: g/L
    arithmetic mean (standard deviation)
        Baseline (N = 20; 22)
    0.200 ( 0.2562 )
    0.286 ( 0.3714 )
        Week 27 (N = 19; 21)
    0.201 ( 0.2809 )
    0.300 ( 0.4153 )
        Week 39 (N = 18; 21)
    0.196 ( 0.3085 )
    0.301 ( 0.4266 )
        Week 53 (N = 20; 21)
    0.196 ( 0.2571 )
    0.383 ( 0.6550 )
        Week 65 (N = 16; 18)
    0.201 ( 0.2521 )
    0.466 ( 0.5624 )
        Week 79 (N = 19; 20)
    0.201 ( 0.2473 )
    0.335 ( 0.4744 )
    No statistical analyses for this end point

    Secondary: Mean Bilirubin Levels

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    End point title
    Mean Bilirubin Levels
    End point description
    Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: micromol/L
    arithmetic mean (standard deviation)
        Baseline (N = 20; 22)
    23.63 ( 12.537 )
    21.12 ( 13.872 )
        Week 27 (N = 19; 21)
    28.69 ( 22.529 )
    24.30 ( 19.209 )
        Week 39 (N = 18; 21)
    24.08 ( 14.258 )
    24.15 ( 16.655 )
        Week 53 (N = 20; 21)
    25.76 ( 17.156 )
    21.32 ( 14.036 )
        Week 65 (N = 16; 18)
    24.51 ( 16.736 )
    20.02 ( 13.808 )
        Week 79 (N = 19; 20)
    23.73 ( 16.161 )
    23.15 ( 17.286 )
    No statistical analyses for this end point

    Secondary: Degree of Hemoglobinuria

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    End point title
    Degree of Hemoglobinuria
    End point description
    The degree of hemoglobinuria was categorized as negative, trace, small, moderate, and large based on the analysis of urine samples collected from each participant at the specified timepoints. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Data is presented for the number of urine samples assessed at each timepoint for the FAS which included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 27, Week 39, Week 53, Week 65, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: Participants
        Baseline: Negative (N = 20; 21)
    17
    21
        Baseline: Trace (N = 20; 21)
    0
    0
        Baseline: Small (N = 20; 21)
    2
    0
        Baseline: Moderate (N = 20; 21)
    0
    0
        Baseline: Large (N = 20; 21)
    1
    0
        Week 27: Negative (N = 19; 21)
    17
    20
        Week 27: Trace (N = 19; 21)
    0
    1
        Week 27: Small (N = 19; 21)
    1
    0
        Week 27: Moderate (N = 19; 21)
    0
    0
        Week 27: Large (N = 19; 21)
    1
    0
        Week 39: Negative (N= 17; 21)
    16
    20
        Week 39: Trace (N= 17; 21)
    1
    1
        Week 39: Small (N= 17; 21)
    0
    0
        Week 39: Moderate (N= 17; 21)
    0
    0
        Week 39: Large (N= 17; 21)
    0
    0
        Week 53: Negative (N = 19; 20)
    16
    19
        Week 53: Trace (N = 19; 20)
    1
    1
        Week 53: Small (N = 19; 20)
    1
    0
        Week 53: Moderate (N = 19; 20)
    1
    0
        Week 53: Large (N = 19; 20)
    0
    0
        Week 65: Negative (N =16; 18)
    15
    17
        Week 65: Trace (N =16; 18)
    0
    1
        Week 65: Small (N = 16; 18)
    0
    0
        Week 65: Moderate (N = 16; 18)
    0
    0
        Week 65: Large (N = 16; 18)
    1
    0
        Week 79: Negative (N = 18; 20)
    16
    19
        Week 79: Trace (N = 18; 20)
    0
    1
        Week 79: Small (N = 18; 20)
    1
    0
        Week 79: Moderate (N = 18; 20)
    0
    0
        Week 79: Large (N = 18; 20)
    1
    0
    No statistical analyses for this end point

    Secondary: Mean Percentage of Type III Erythrocytes

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    End point title
    Mean Percentage of Type III Erythrocytes
    End point description
    As a measure of hemolysis the mean percentage of Type III erythrocytes was measured at the specified timepoints. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 27, Week 39, Week 53, Week 65 and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: Percentage of Type III Erythrocytes
    arithmetic mean (standard deviation)
        Baseline (N = 18; 21)
    39.9197 ( 25.36275 )
    36.7478 ( 29.93810 )
        Week 27 (N = 17; 21)
    40.9121 ( 23.17684 )
    40.1304 ( 30.01551 )
        Week 39 (N = 16; 20)
    41.2158 ( 24.81071 )
    43.3663 ( 29.65777 )
        Week 53 (N = 19; 21)
    41.8196 ( 23.23819 )
    40.4676 ( 31.14150 )
        Week 65 (N = 15; 17)
    39.1192 ( 22.20104 )
    37.5379 ( 28.76642 )
        Week 79 (N = 15; 16)
    43.7609 ( 21.51712 )
    42.5501 ( 30.20582 )
    No statistical analyses for this end point

    Secondary: LDH Levels at Week 53 and Week 79

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    End point title
    LDH Levels at Week 53 and Week 79
    End point description
    The analysis of the crossover comparison of hemolysis, as measured by LDH at Week 53 and Week 79. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Week 53 (first week of Period 2) and Week 79 (last week of Period 2)
    End point values
    ABP 959 Eculizumab
    Number of subjects analysed
    39
    40
    Units: U/L
        least squares mean (confidence interval 95%)
    209.95 (183.817 to 239.802)
    203.56 (178.387 to 232.295)
    Statistical analysis title
    GMR (ABP 959/Eculizumab)
    Comparison groups
    ABP 959 v Eculizumab
    Number of subjects included in analysis
    79
    Analysis specification
    Pre-specified
    Analysis type
    other
    Method
    Parameter type
    GMR
    Point estimate
    1.0314
    Confidence interval
         level
    97.5%
         sides
    1-sided
         lower limit
    -
         upper limit
    1.1201

    Secondary: Mean LDH Levels by Visit up to Week 79

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    End point title
    Mean LDH Levels by Visit up to Week 79
    End point description
    Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS with data available at each time point. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 3, Week 7, Week 13, Week 15, Week 19, Week 25, Week 27, Week 29, Week 33, Week 39, Week 41, Week 43, Week 45, Week 47, Week 49, Week 51, Week 53, Week 55, Week 59, Week 65, Week 67, Week 69, Week 71, Week 73, Week 75, Week 77, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: U/L
    arithmetic mean (standard deviation)
        Baseline (N = 20; 22)
    199.7 ( 61.06 )
    193.9 ( 45.09 )
        Week 3 (N = 19; 20)
    210.7 ( 77.80 )
    185.8 ( 42.22 )
        Week 7 (N = 19; 21)
    201.4 ( 48.41 )
    194.0 ( 38.33 )
        Week 13 (N = 18; 21)
    207.7 ( 76.14 )
    206.2 ( 63.82 )
        Week 15 (N = 17; 22)
    213.4 ( 105.86 )
    197.0 ( 55.63 )
        Week 19 (N = 19; 21)
    188.5 ( 27.58 )
    201.0 ( 59.21 )
        Week 25 (N = 18; 21)
    230.5 ( 76.07 )
    190.2 ( 46.91 )
        Week 27 (N = 18; 20)
    191.7 ( 35.99 )
    192.2 ( 63.83 )
        Week 29 (N = 19; 21)
    207.2 ( 50.35 )
    202.1 ( 58.46 )
        Week 33 (N = 17; 20)
    194.6 ( 29.36 )
    206.8 ( 59.44 )
        Week 39 (N = 18; 21)
    188.1 ( 37.55 )
    196.9 ( 66.73 )
        Week 41 (N = 19; 21)
    196.1 ( 49.21 )
    199.7 ( 51.00 )
        Week 43 (N = 18; 21)
    215.9 ( 62.41 )
    207.1 ( 79.95 )
        Week 45 (N = 19; 21)
    202.8 ( 53.15 )
    199.4 ( 66.14 )
        Week 47 (N = 19; 20)
    199.4 ( 51.72 )
    197.6 ( 65.25 )
        Week 49 (N = 19; 21)
    216.2 ( 111.26 )
    203.2 ( 68.65 )
        Week 51 (N = 19; 21)
    229.9 ( 125.47 )
    197.7 ( 57.02 )
        Week 53 (N = 20; 21)
    224.0 ( 64.49 )
    184.7 ( 46.32 )
        Week 55 (N = 18; 19)
    213.9 ( 103.58 )
    188.0 ( 48.91 )
        Week 59 (N = 19; 18)
    209.4 ( 98.42 )
    191.4 ( 79.01 )
        Week 65 (N = 16; 18)
    230.6 ( 135.26 )
    180.9 ( 55.50 )
        Week 67 (N = 19; 17)
    196.1 ( 40.61 )
    186.2 ( 50.57 )
        Week 69 (N = 19; 17)
    200.1 ( 38.12 )
    186.2 ( 38.48 )
        Week 71 (N = 18; 18)
    196.8 ( 36.36 )
    186.6 ( 48.02 )
        Week 73 (N = 19; 19)
    210.3 ( 43.90 )
    181.9 ( 49.31 )
        Week 75 (N = 17; 19)
    207.9 ( 67.51 )
    191.4 ( 65.08 )
        Week 77 (N = 14; 20)
    209.6 ( 54.35 )
    181.4 ( 38.72 )
        Week 79 (N = 19; 19)
    229.2 ( 116.85 )
    185.8 ( 45.11 )
    No statistical analyses for this end point

    Secondary: Mean number of packed RBC Units Transfused per Month

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    End point title
    Mean number of packed RBC Units Transfused per Month
    End point description
    Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Results are presented for participants in the FAS who had packed RBC units transfused. The FAS included all randomized participants.
    End point type
    Secondary
    End point timeframe
    Baseline to End of Study (up to Week 79)
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    2
    6
    Units: packed RBC units per month
        arithmetic mean (standard deviation)
    0.200 ( 0.1980 )
    0.238 ( 0.2078 )
    No statistical analyses for this end point

    Secondary: Total and Unbound Pharmacokinetics (PK) Area Under the Curve (AUC) of ABP 959 and Eculizumab From Week 13 to Week 15 (Period 1)

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    End point title
    Total and Unbound Pharmacokinetics (PK) Area Under the Curve (AUC) of ABP 959 and Eculizumab From Week 13 to Week 15 (Period 1)
    End point description
    The total and unbound PK concentration AUC values from Week 13 to Week 15 in Period 1 are presented by actual treatment received. The PK parameter analysis set consisted of a subset of participants from the safety analysis set with an evaluable ABP 959 or eculizumab serum concentration time profile from Week 13 to Week 15
    End point type
    Secondary
    End point timeframe
    PK samples were collected predose and immediately postdose Week 13, 7 days post the Week 13 dose (Week 14), and predose at Week 15
    End point values
    ABP 959 Eculizumab
    Number of subjects analysed
    18
    19
    Units: µg*day/mL
    geometric mean (geometric coefficient of variation)
        Total PK AUC
    3898.05 ( 37.5 )
    4273.28 ( 30.6 )
        Unbound PK AUC
    2761.19 ( 51.3 )
    2903.93 ( 40.6 )
    Statistical analysis title
    Unbound PK AUC GMR (ABP 959/Eculizumab)
    Comparison groups
    ABP 959 v Eculizumab
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    GMR
    Point estimate
    0.9508
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.7454
         upper limit
    1.213
    Statistical analysis title
    Total PK AUC GMR (ABP 959/Eculizumab)
    Comparison groups
    ABP 959 v Eculizumab
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    Method
    Parameter type
    GMR
    Point estimate
    0.9122
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.7586
         upper limit
    1.0968

    Secondary: Total and Unbound Trough Serum Concentrations of ABP 959 and Eculizumab

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    End point title
    Total and Unbound Trough Serum Concentrations of ABP 959 and Eculizumab
    End point description
    The total and unbound serum trough concentrations are presented by treatment sequence received for the prespecified time points. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. The PK concentration analysis set consisted of a subset of participants from the safety analysis set with at least one serum concentration (including results below the quantifiable limit) of ABP 959 or eculizumab, with data analyzed according to actual treatment received. Participants with data available at each time point are presented.
    End point type
    Secondary
    End point timeframe
    PK samples were collected predose at the prespecified timepoints: baseline, Week 3, Week 7, Week 13, Week 15, Week 19, Week 27, Week 33, Week 39, Week 45, Week 51, Week 53, Week 55, Week 59, Week 65, Week 71, Week 77, and Week 79
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: µg/mL
    geometric mean (geometric coefficient of variation)
        Baseline: Total (N = 20; 22)
    200.15 ( 52.8 )
    202.58 ( 44.3 )
        Baseline: Unbound (N = 20; 22)
    94.62 ( 100.1 )
    117.48 ( 71.5 )
        Week 3: Total (N = 20; 21)
    205.25 ( 48.8 )
    197.67 ( 42.9 )
        Week 3: Unbound (N = 20; 21)
    113.99 ( 91.5 )
    116.87 ( 68.9 )
        Week 7: Total (N = 20; 20)
    213.51 ( 50.1 )
    194.80 ( 42.5 )
        Week 7: Unbound (N = 20; 20)
    116.57 ( 92.1 )
    98.34 ( 108.9 )
        Week 13: Total (N = 20; 21)
    215.54 ( 55.8 )
    201.60 ( 45.6 )
        Week 13: Unbound (N = 20; 21)
    114.40 ( 98.4 )
    123.73 ( 69.1 )
        Week 15: Total (N = 18; 21)
    192.80 ( 49.1 )
    205.07 ( 36.9 )
        Week 15: Unbound (N = 18; 21)
    98.68 ( 87.0 )
    123.11 ( 66.1 )
        Week 19: Total (N = 19; 21)
    216.46 ( 46.3 )
    200.51 ( 49.1 )
        Week 19: Unbound (N = 19; 21)
    133.39 ( 75.2 )
    120.54 ( 77.3 )
        Week 25: Total (N = 18; 21)
    217.75 ( 50.2 )
    200.59 ( 51.7 )
        Week 25: Unbound (N = 18; 21)
    134.37 ( 95.5 )
    112.73 ( 96.4 )
        Week 27: Total (N = 19; 21)
    198.17 ( 58.9 )
    203.19 ( 45.3 )
        Week 27: Unbound (N = 19; 21)
    112.02 ( 111.0 )
    122.00 ( 83.8 )
        Week 33: Total (N = 17; 21)
    211.62 ( 55.5 )
    196.57 ( 49.1 )
        Week 33: Unbound (N = 17; 21)
    130.12 ( 117.3 )
    126.36 ( 78.4 )
        Week 39: Total (N = 17; 21)
    183.57 ( 68.3 )
    201.47 ( 48.1 )
        Week 39: Unbound (N = 17; 21)
    131.50 ( 104.8 )
    129.89 ( 75.1 )
        Week 45: Total (N = 18; 21)
    204.62 ( 52.7 )
    197.67 ( 47.9 )
        Week 45: Unbound (N = 18; 21)
    130.30 ( 92.0 )
    126.36 ( 77.3 )
        Week 51: Total (N = 18; 21)
    207.20 ( 59.6 )
    200.41 ( 45.5 )
        Week 51: Unbound (N = 18; 21)
    130.32 ( 117.4 )
    123.27 ( 68.3 )
        Week 53: Total (N = 20; 21)
    193.77 ( 54.4 )
    198.89 ( 46.3 )
        Week 53: Unbound (N = 20; 21)
    108.40 ( 130.3 )
    124.82 ( 74.6 )
        Week 55: Total (N = 19; 20)
    210.22 ( 59.0 )
    185.34 ( 48.4 )
        Week 55: Unbound (N = 19; 20)
    132.20 ( 125.4 )
    117.93 ( 77.2 )
        Week 59: Total (N = 19; 20)
    184.38 ( 58.9 )
    192.66 ( 46.6 )
        Week 59: Unbound (N = 19; 20)
    111.48 ( 121.5 )
    122.01 ( 78.5 )
        Week 65: Total (N = 16; 18)
    190.09 ( 62.0 )
    202.83 ( 51.5 )
        Week 65: Unbound (N = 16; 18)
    110.57 ( 146.9 )
    120.72 ( 87.7 )
        Week 71: Total (N = 17; 16)
    160.43 ( 99.5 )
    188.05 ( 58.6 )
        Week 71: Unbound (N = 17; 16)
    101.66 ( 156.7 )
    104.82 ( 115.0 )
        Week 77: Total (N = 15; 17)
    211.80 ( 47.2 )
    198.24 ( 54.8 )
        Week 77: Unbound (N = 15; 17)
    140.07 ( 98.3 )
    111.83 ( 99.8 )
        Week 79: Total (N = 18; 20)
    178.29 ( 60.7 )
    199.91 ( 50.0 )
        Week 79: Unbound (N = 18; 20)
    101.98 ( 133.1 )
    116.28 ( 96.5 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
    End point description
    TEAEs are any adverse event (AE) that began or increased in severity or frequency at or after the time of first treatment up to end of study (up to Week 79). A treatment-emergent serious adverse event (SAE) was a TEAE that met at least 1 of the following criteria: was fatal, life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was another medically important serious event. The treatment-emergent events of interest (EOI) prespecified for this study included serious infections (meningococcus aspergillus, and other serious infections/sepsis), and infusion reactions. The safety analysis set included all treated participants, with treatment assigned based on actual treatment received.
    End point type
    Secondary
    End point timeframe
    Day 1 to End of Study (up to Week 79)
    End point values
    Eculizumab ABP 959
    Number of subjects analysed
    42
    41
    Units: Participants
        All TEAEs
    39
    33
        Any Treatment-emergent SAE
    2
    7
        Any Treatment-emergent EOI: Infusion reaction
    15
    15
        Any Treatment-emergent EOI: Serious infection
    0
    3
    No statistical analyses for this end point

    Secondary: Number of Participants with Antidrug Antibodies (ADAs)

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    End point title
    Number of Participants with Antidrug Antibodies (ADAs)
    End point description
    Any samples that tested positive for binding antibodies were also tested for neutralizing antibodies. Treatment boosted ADAs were defined as a positive immunoassay result at baseline and at least 1 postbaseline immunoassay result that was ≥ 4 times the magnitude of the baseline result. Baseline was defined as the last non-missing assessment taken prior to the first dose of IP. Ab = antibody; NAb = neutralizing antibody; +ve = positive; -ve = negative; BL = baseline
    End point type
    Secondary
    End point timeframe
    Blood samples for ADA assessments were taken predose at baseline, Week 3, Week 7, Week 13, Week 19, Week 25, Week 27, Week 33, Week 39, Week 45, Week 51, Week 53, Week 55, Week 59, Week 65, Week 71, Week 77 and Week 79.
    End point values
    ABP 959/Eculizumab Eculizumab/ABP 959
    Number of subjects analysed
    20
    22
    Units: Participants
        Binding Ab +ve anytime
    0
    2
        NAb +ve anytime
    0
    0
        Binding Ab +ve at/before BL
    0
    0
        NAb +ve at/before BL
    0
    0
        Treatment boosted Ab +ve
    0
    0
        Binding Ab +ve post-BL with -ve/no result at BL
    0
    2
        NAb +ve post-BL with -ve/no result at BL
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 to End of Study (up to Week 79)
    Adverse event reporting additional description
    All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Period 1: ABP 959
    Reporting group description
    Participants received ABP 959 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1.

    Reporting group title
    Period 2: ABP 959
    Reporting group description
    Participants received ABP 959 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Reporting group title
    Period 2: Eculizumab
    Reporting group description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 26 weeks in Period 2.

    Reporting group title
    Period 1: Eculizumab
    Reporting group description
    Participants received eculizumab 900 mg administered IV every 14 ± 2 days for 52 weeks in Period 1.

    Serious adverse events
    Period 1: ABP 959 Period 2: ABP 959 Period 2: Eculizumab Period 1: Eculizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 20 (15.00%)
    4 / 21 (19.05%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Meniscus injury
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 22 (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
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (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
    Vertigo CNS origin
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    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
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (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
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (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
    COVID-19
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 22 (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
    Period 1: ABP 959 Period 2: ABP 959 Period 2: Eculizumab Period 1: Eculizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 20 (75.00%)
    17 / 21 (80.95%)
    18 / 20 (90.00%)
    20 / 22 (90.91%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lipoma
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    5 / 22 (22.73%)
         occurrences all number
    0
    0
    1
    5
    Flushing
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hypotension
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 21 (9.52%)
    3 / 20 (15.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    2
    4
    2
    Chills
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Catheter site pruritus
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    0
    1
    Fatigue
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    2 / 22 (9.09%)
         occurrences all number
    2
    3
    1
    3
    Influenza like illness
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    4
    0
    0
    2
    Pyrexia
         subjects affected / exposed
    6 / 20 (30.00%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    9
    4
    2
    1
    Pain
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    2
    Malaise
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Reproductive system and breast disorders
    Vaginal discharge
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Intermenstrual bleeding
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    0
    2
    Dyspnoea
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    1
    1
    Cough
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    3 / 22 (13.64%)
         occurrences all number
    2
    2
    1
    3
    Sinonasal obstruction
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Vitamin D decreased
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Weight increased
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Contusion
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    1
    4
    Vaccination complication
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 21 (9.52%)
    2 / 20 (10.00%)
    5 / 22 (22.73%)
         occurrences all number
    1
    2
    2
    6
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nervous system disorders
    Vertigo CNS origin
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Somnolence
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Migraine
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    3 / 20 (15.00%)
    2 / 21 (9.52%)
    1 / 20 (5.00%)
    9 / 22 (40.91%)
         occurrences all number
    3
    2
    2
    11
    Dizziness
         subjects affected / exposed
    2 / 20 (10.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    2
    3
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 20 (20.00%)
    3 / 21 (14.29%)
    1 / 20 (5.00%)
    4 / 22 (18.18%)
         occurrences all number
    5
    3
    1
    12
    Haemolysis
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    2 / 20 (10.00%)
    2 / 22 (9.09%)
         occurrences all number
    3
    0
    5
    3
    Thrombocytopenia
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    3
    0
    2
    Neutropenia
         subjects affected / exposed
    1 / 20 (5.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    2
    3
    0
    2
    Leukopenia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    2
    Eye disorders
    Eye pruritus
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Neovascular age-related macular degeneration
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Haemorrhoids
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Nausea
         subjects affected / exposed
    3 / 20 (15.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    3
    0
    1
    1
    Dyspepsia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 20 (15.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    4
    2
    1
    2
    Abdominal pain upper
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 21 (9.52%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    2
    0
    2
    Abdominal pain
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Abdominal distension
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Cholecystitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Ocular icterus
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    8
    0
    0
    1
    Skin and subcutaneous tissue disorders
    Rash pruritic
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Pruritus
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    2
    1
    2
    Erythema
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    2
    Eczema
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    2
    1
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Haemoglobinuria
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Chromaturia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    1
    1
    2
    Bilirubinuria
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 21 (4.76%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    3
    1
    0
    1
    Arthritis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Back pain
         subjects affected / exposed
    2 / 20 (10.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    2
    1
    1
    Flank pain
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    0
    1
    Muscle fatigue
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Enterovirus infection
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gingivitis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Influenza
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Lyme disease
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    5 / 20 (25.00%)
    4 / 21 (19.05%)
    1 / 20 (5.00%)
    2 / 22 (9.09%)
         occurrences all number
    8
    4
    1
    3
    Pharyngitis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cystitis
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    1
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    0
    1
    COVID-19
         subjects affected / exposed
    0 / 20 (0.00%)
    3 / 21 (14.29%)
    5 / 20 (25.00%)
    1 / 22 (4.55%)
         occurrences all number
    0
    3
    5
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
    1 / 20 (5.00%)
    1 / 22 (4.55%)
         occurrences all number
    1
    1
    1
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Wound infection
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
    0 / 20 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Vitamin B12 deficiency
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
    1 / 20 (5.00%)
    0 / 22 (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
    17 Sep 2018
    - To allow randomization ≤ 8 days before the first dose of IP administration and add RBC transfusion received within the last 12 months as stratification factor. - To update text describing dosing schedule for participants who require dose adjustments for IP based on signs and symptoms of intravascular hemolysis, including LDH levels. - To update statistical sections - To clarify study discontinuation procedures for participants who develop meningococcal infection, who become pregnant, or who require continuous dose adjustments for IP. - To clarify urine collection for hemoglobinuria assessment. - To add dates for concomitant medications. - To remove outcome from blood transfusion data collected. - To clarify laboratory testing category for hemolysis-related laboratory tests. - To update site geographical regions. - To update inclusion/exclusion criteria. - To update sampling schedule for serum chemistry, hematology, hemolysis-related tests, and coagulation. - To add follow-up period information. - To reduce liver Doppler ultrasound assessments to screening only. - To add and clarify C-reactive protein sample collection.
    29 Apr 2019
    - To update the planned number of sites from 12 to 25 and to clarify that the study would be performed globally and not only in Europe. - To update the planned study duration from approximately 24 months to approximately 27 months. - To update the planned study start and end dates. - To remove subgroup analyses by age and ethnicity for the safety analysis set.
    05 Mar 2020
    - To update the number of planned study sites from 25 to 45. - To update the threshold of the aggregated intra-subject coefficient of variation (CV). - To update the primary endpoint for the crossover comparison to include an additional assessment period. - To add the End of Study definition as last participant, last visit. - To clarify text in the Prior and Concomitant Therapy section to include prophylactic antibiotics as concomitant medications. - To update the timing the first blinded interim check of CV. - To clarify the criteria for discontinuation.

    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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