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    Clinical Trial Results:
    Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult And Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

    Summary
    EudraCT number
    		 2016-002027-29
    Trial protocol
    		 GB   DE   AT   ES   SE   BE   CZ   IT  
    Global end of trial date
    24 Jan 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    09 Feb 2024
    First version publication date
    22 Jul 2022
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    ALXN1210-aHUS-311
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02949128
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Alexion Pharmaceuticals Inc.
    Sponsor organisation address
    100 College Street, New Haven, CT, United States, 06510
    Public contact
    Alexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 787148158, clinicaltrials.eu@alexion.com
    Scientific contact
    Alexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 787148158, clinicaltrials.eu@alexion.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 Feb 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Jan 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of the study is to assess the safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor.
    Protection of trial subjects
    This trial was conducted in compliance with Good Clinical Practice.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Mar 2017
    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
    Australia: 4
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Japan: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 8
    Country: Number of subjects enrolled
    Russian Federation: 2
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Taiwan: 3
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    United States: 5
    Worldwide total number of subjects
    58
    EEA total number of subjects
    27
    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)
    49
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The study included 2 periods: Initial evaluation period and Extension period.

    Period 1
    Period 1 title
    Initial Evaluation Period (26 Weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Ravulizumab
    Arm description
    		 Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Evaluation Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter. After the Initial Evaluation Period, participants entered an Extension Period and received ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received ravulizumab at prespecified dose and timepoints.

    Number of subjects in period 1
    		Ravulizumab
    Started
    58
    Received At Least 1 Dose of Study Drug
    58
    Completed
    49
    Not completed
    9
         Adverse event, serious fatal
    2
         Physician decision
    1
         Adverse event, non-fatal
    3
         Failed to Meet Eligibility Criteria
    2
         Protocol deviation
    1
    Period 2
    Period 2 title
    Extension Period (Up to 4.5 Years)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Ravulizumab
    Arm description
    		 Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Evaluation Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter. After the Initial Evaluation Period, participants entered an Extension Period and received ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received ALXN1210 at prespecified dose and timepoints.

    Number of subjects in period 2
    		Ravulizumab
    Started
    49
    Received At Least 1 Dose of Study Drug
    47
    Completed
    28
    Not completed
    21
         Consent withdrawn by subject
    9
         Physician decision
    5
         Death
    1
         Other than specified
    5
         Protocol deviation
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ravulizumab
    Reporting group description
    		 Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Evaluation Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter. After the Initial Evaluation Period, participants entered an Extension Period and received ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.

    Reporting group values
    		 Ravulizumab Total
    Number of subjects
    		 58 58
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 49 49
        From 65-84 years
    		 9 9
        85 years and over
    		 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 43.4 ( 16.04 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 39 39
        Male
    		 19 19
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 3
        Not Hispanic or Latino
    		 42 42
        Unknown or Not Reported
    		 13 13
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 1
        Asian
    		 16 16
        Native Hawaiian or Other Pacific Islander
    		 0 0
        Black or African American
    		 2 2
        White
    		 30 30
        More than one race
    		 1 1
        Unknown or Not Reported
    		 8 8

    End points

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    End points reporting groups
    Reporting group title
    Ravulizumab
    Reporting group description
    		 Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Evaluation Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter. After the Initial Evaluation Period, participants entered an Extension Period and received ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.
    Reporting group title
    Ravulizumab
    Reporting group description
    		 Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Evaluation Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter. After the Initial Evaluation Period, participants entered an Extension Period and received ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.

    Primary: Percentage Of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26

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    End point title
    		 Percentage Of Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 [1]
    End point description
    Complete TMA response during 26-week Initial Evaluation Period is a composite endpoint that required normalization of hematological parameters and improvement in kidney function (≥25% reduction in serum creatinine from baseline); for participants on dialysis, baseline was established at least 6 days after end of dialysis. Participants had to meet these criteria for 2 separate assessments obtained at least 4 weeks apart, and any measurement in between. For a responder, latest time point a participant could first meet response criteria was 28 days before the Week 26 assessment. % was based on responders among treated participants. 95% CI: based on asymptotic Gaussian approximation method with a continuity correction. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria. Number of Participants Analyzed signifies participants evaluable for this endpoint.
    End point type
    Primary
    End point timeframe
    Week 26
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analyses was planned to be reported for this endpoint.
    End point values
    		 Ravulizumab
    Number of subjects analysed
    56
    Units: percentage of participants
    number (confidence interval 95%)
        Complete TMA Response
    53.6 (39.6 to 67.5)
        Platelet count normalization
    83.9 (73.4 to 94.4)
        LDH normalization
    76.8 (64.8 to 88.7)
        ≥25% improvement in serum creatinine from baseline
    58.9 (45.2 to 72.7)
    No statistical analyses for this end point

    Secondary: Time To Complete TMA Response

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    End point title
    		 Time To Complete TMA Response
    End point description
    Participants that did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed. The time to complete TMA Response is reported in days. The time of the event of a confirmed complete TMA response was considered the first time point at which all the criteria for complete TMA response were met. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, and met pre-specified eligibility criteria. Here, Overall Number of Participants analyzed (N) signifies those who were evaluable for this endpoint. 99999 signifies that the data were not available.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 114
    End point values
    		 Ravulizumab
    Number of subjects analysed
    56
    Units: days
        median (inter-quartile range (Q1-Q3))
    86.0 (42.0 to 99999)
    No statistical analyses for this end point

    Secondary: Proportion Of Participants With Complete TMA Response At Week 52

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    End point title
    		 Proportion Of Participants With Complete TMA Response At Week 52
    End point description
    The proportion of participants considered responders, along with a 2-sided 95% CI for the Week 52 time point, is reported. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment (components of the response maintained for at least 28 days). Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at specified timepoint (Week 52).
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    44
    Units: proportion of participants
    number (confidence interval 95%)
        Complete TMA Response
    0.500 (0.346 to 0.654)
        Platelet Count Normalization
    0.909 (0.783 to 0.975)
        LDH Normalization
    0.750 (0.597 to 0.868)
        ≥25% improvement in serum creatinine from baseline
    0.659 (0.501 to 0.795)
    No statistical analyses for this end point

    Secondary: Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Weeks 26 and 52

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    End point title
    		 Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Weeks 26 and 52
    End point description
    Kidney function evaluated by eGFR was summarized at baseline and Week 26 and Week 52 time points using descriptive statistics for continuous variables for the observed value, as well as change from baseline. Baseline value was defined as average of values from assessments performed prior to first study drug infusion (these could include results from Screening and Day 1 visit). A value of 10 mL/min/1.73 meters squared (m^2) for eGFR was imputed for participants requiring dialysis for acute kidney injury. The observed value and change from baseline are reported in mL/min/1.73 m^2. An increase indicated improvement in kidney function. FAS: all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here,"N" signifies those who were evaluable for this endpoint and "n" signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    48
    Units: mL/min/1.73 m^2
    median (full range (min-max))
        Baseline (n=48)
    10.00 (4 to 80)
        Change From Baseline at Week 26 (n=47)
    29.00 (-13 to 108)
        Change From Baseline at Week 52 (n=43)
    23.00 (-13 to 95)
    No statistical analyses for this end point

    Secondary: Participants Who Do Not Require Dialysis at Weeks 26 and 52

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    End point title
    		 Participants Who Do Not Require Dialysis at Weeks 26 and 52
    End point description
    For participants requiring dialysis within 5 days prior to ALXN1210 treatment initiation, the number of participants no longer requiring dialysis is reported. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at specified timepoint. Here, Overall Number of Participants analyzed (N) signifies those who were evaluable for this endpoint and Number Analyzed (n) signifies participants evaluable at specified time points.
    End point type
    Secondary
    End point timeframe
    Week 26 and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    24
    Units: Participants
        Week 26 (n=24)
    16
        Week 52 (n=22)
    16
    No statistical analyses for this end point

    Secondary: Participants With Change From Baseline In CKD Stage At Weeks 26 and 52

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    End point title
    		 Participants With Change From Baseline In CKD Stage At Weeks 26 and 52
    End point description
    The CKD stage is presented as change from baseline in participants that Improved (excluding those with Stage 1 [normal renal function] at baseline as they cannot improve), Worsened (excluding those with Stage 5 at baseline as they cannot worsen), and Stayed the Same, compared to CKD stage at baseline. Baseline was derived based on the last available eGFR before starting treatment. Stage 5 was considered worst category, while Stage 1 was considered best category. A 2-sided 95% CI for the proportion, based on exact confidence limits using the Clopper-Pearson method, was provided for each category. FAS: all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, "N" signifies those who were evaluable for this endpoint and “n” signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26, and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    47
    Units: participants
        Week 26, Improved (n=47)
    32
        Week 26, Worsened (n=47)
    2
        Week 26, Stayed the Same (n=47)
    13
        Week 52, Improved (n=43)
    30
        Week 52, Worsened (n=12)
    2
        Week 52, Stayed the Same (n=43)
    11
    No statistical analyses for this end point

    Secondary: Change From Baseline In Platelet Count At Weeks 26 and 52

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    End point title
    		 Change From Baseline In Platelet Count At Weeks 26 and 52
    End point description
    The hematologic TMA parameter of platelet count was summarized at baseline and at Week 26 and Week 52 using descriptive statistics for continuous variables for the change from baseline. Results are reported in platelets*10^9/liter (L) blood. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoints (Week 26 or 52). Here, "N" signifies those who were evaluable for this endpoint and “n” signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    56
    Units: platelets*10^9/L
    median (full range (min-max))
        Baseline (n=56)
    95.25 (18 to 473)
        Change From Baseline at Week 26 (n=48)
    125.00 (-126 to 338)
        Change From Baseline at Week 52 (n=44)
    126.25 (-51.5 to 335)
    No statistical analyses for this end point

    Secondary: Change From Baseline In LDH At Weeks 26 and 52

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    End point title
    		 Change From Baseline In LDH At Weeks 26 and 52
    End point description
    The hematologic TMA parameter of serum LDH was summarized at baseline and at Week 26 and Week 52 using descriptive statistics for continuous variables for the change from baseline. Results are reported in units (U)/L. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoints (Week 26 or 52). Here, "N" signifies those who were evaluable for this endpoint and “n” signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    56
    Units: U/L
    median (full range (min-max))
        Baseline (n=56)
    508.00 (229.5 to 3249)
        Change From Baseline at Week 26 (n=48)
    -310.75 (-3072 to 8.5)
        Change From Baseline at Week 52 (n=44)
    -293.75 (-3107 to 81)
    No statistical analyses for this end point

    Secondary: Change From Baseline In Hemoglobin At Weeks 26 and 52

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    End point title
    		 Change From Baseline In Hemoglobin At Weeks 26 and 52
    End point description
    The hematologic TMA parameter of hemoglobin level was summarized at baseline and at Week 26 and Week 52 using descriptive statistics for continuous variables for the change from baseline. Results are reported in grams (g)/L. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoints (Week 26 or 52). Here, "N" signifies those who were evaluable for this endpoint and “n” signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    56
    Units: g/L
    median (full range (min-max))
        Baseline (n=56)
    85.00 (60.5 to 140)
        Change From Baseline at Week 26 (n=56)
    35.00 (-9 to 69)
        Change From Baseline at Week 52 (n=44)
    41.75 (-25 to 83.5)
    No statistical analyses for this end point

    Secondary: Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin ≥20 g/L Through Week 26 and Week 52

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    End point title
    		 Percentage Of Complement Inhibitor Treatment-naïve Participants With An Increase From Baseline In Hemoglobin ≥20 g/L Through Week 26 and Week 52
    End point description
    The percentage of participants with an increase from baseline in hemoglobin ≥20 g/L, observed at 2 separate assessments obtained at least 4 weeks apart, and any measurement in between, was assessed through Week 26 and Week 52 and is presented as the percentage of responders, along with a 2-sided 95% CI. To be considered a responder during the 26-week and 52-week Extension Periods, the latest time point a participant could first meet the response criteria was 28 days before the respective Week 26 and Week 52 assessments (components of the response maintained for at least 28 days). FAS: all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoints (Week 26 or 52). Here, "N" signifies those who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 26 and through Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    38
    Units: percentage of participants
    number (confidence interval 95%)
        Week 26
    75.5 (61.1 to 86.7)
        Week 52
    86.4 (72.6 to 94.8)
    No statistical analyses for this end point

    Secondary: Change From Baseline In Quality Of Life As Measured By The EuroQol 5-Dimension 3-Level (EQ-5D-3L) At Weeks 26 and 52

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    End point title
    		 Change From Baseline In Quality Of Life As Measured By The EuroQol 5-Dimension 3-Level (EQ-5D-3L) At Weeks 26 and 52
    End point description
    The EQ-5D-3L is a participant-answered questionnaire that scores 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (scored as a 1, 2, or 3, with 3 being the worst health state), as well as health state on a visual analogue scale (0 to 100, with 100 representing the best health state). From these scores, a summary index score is derived using the time trade-off valuation set for the United States and ranges from -1 to 1, where a score above 0.94 indicates full health. An increase in score from baseline indicates improvement in quality of life. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, "N" signifies those who were evaluable for this endpoint and “n” signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    53
    Units: units on a scale
    median (full range (min-max))
        Baseline (n=53)
    0.59 (-0.113 to 0.753)
        Change from Baseline at Week 26 (n=46)
    0.15 (-0.138 to 0.723)
        Change from Baseline at Week 52 (n=42)
    0.26 (-0.143 to 0.707)
    No statistical analyses for this end point

    Secondary: Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire At Weeks 26 and 52

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    End point title
    		 Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire At Weeks 26 and 52
    End point description
    Quality of life was evaluated in part using FACIT Fatigue Version 4. The data were summarized at baseline and at the Week 26 and Week 52 time point using descriptive statistics for continuous variables. The FACIT Fatigue Version 4 questionnaire at baseline and the Week 52 timepoint was scored using standard scoring algorithms. The score ranges from 0-52, with a higher score indicating less Fatigue. An increase in score indicated an improvement in quality of life. Full Analysis Set (FAS): all participants who received at least 1 dose of ravulizumab, had at least 1 post-baseline efficacy assessment, met pre-specified eligibility criteria, and had evaluable data at the specified timepoint (Week 26 or Week 52). Here, "N" signifies those who were evaluable for this endpoint and “n” signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Ravulizumab
    Number of subjects analysed
    48
    Units: units on a scale
    median (full range (min-max))
        Baseline (n=48)
    24.00 (0 to 51)
        Change From Baseline at Week 26 (n=44)
    20.00 (-16 to 48)
        Change From Baseline at Week 52 (n=40)
    16.50 (-17 to 50)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the beginning of the initial evaluation period (Day1) up to 4.5 years
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Ravulizumab
    Reporting group description
    		 Participants received weight-based dosages of ravulizumab for 26 weeks during the Initial Evaluation Period. Participants received a loading dose of ravulizumab intravenously on Day 1, followed by maintenance dosing on Day 15 and once every 8 weeks thereafter. After the Initial Evaluation Period, participants entered an Extension Period and received ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.

    Serious adverse events
    		 Ravulizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    38 / 58 (65.52%)
         number of deaths (all causes)
    4
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Arteriovenous fistula
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Nephrectomy
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Kidney transplant rejection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transplant rejection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Milk allergy
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Hypoxia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Acute pulmonary oedema
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Product issues
    Device leakage
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Biopsy kidney
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Seroma
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shunt occlusion
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vascular access site thrombosis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shunt thrombosis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post procedural complication
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Shunt stenosis
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Ventricular arrhythmia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Lacunar infarction
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cervicobrachial syndrome
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Atypical haemolytic uraemic syndrome
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune thrombocytopenia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Vitreous haemorrhage
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vitreous disorder
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Toothache
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancreatitis relapsing
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis bullous
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal haematoma
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Renal pseudoaneurysm
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    End stage renal disease
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pharyngitis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritonitis bacterial
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Fungaemia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 58 (8.62%)
         occurrences causally related to treatment / all
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    2 / 58 (3.45%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 2
    Escherichia pyelonephritis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Large intestine infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hantaviral infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterovirus infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Stenotrophomonas infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterococcal infection
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypervolaemia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 58 (1.72%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ravulizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    56 / 58 (96.55%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    13 / 58 (22.41%)
         occurrences all number
    21
    Hypotension
         subjects affected / exposed
    6 / 58 (10.34%)
         occurrences all number
    7
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    13 / 58 (22.41%)
         occurrences all number
    14
    Oedema peripheral
         subjects affected / exposed
    11 / 58 (18.97%)
         occurrences all number
    20
    Fatigue
         subjects affected / exposed
    9 / 58 (15.52%)
         occurrences all number
    10
    Pain
         subjects affected / exposed
    5 / 58 (8.62%)
         occurrences all number
    6
    Asthenia
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    8
    Face oedema
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Catheter site pain
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    5 / 58 (8.62%)
         occurrences all number
    7
    Reproductive system and breast disorders
    Intermenstrual bleeding
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Ovarian cyst
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    12 / 58 (20.69%)
         occurrences all number
    13
    Dyspnoea
         subjects affected / exposed
    11 / 58 (18.97%)
         occurrences all number
    17
    Epistaxis
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Oropharyngeal pain
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Productive cough
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    8 / 58 (13.79%)
         occurrences all number
    13
    Insomnia
         subjects affected / exposed
    5 / 58 (8.62%)
         occurrences all number
    5
    Depression
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    5
    Delirium
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 58 (8.62%)
         occurrences all number
    8
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    5
    Blood creatinine increased
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Weight decreased
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    5
    Fall
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Infusion related reaction
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    4
    Skin abrasion
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    7
    Somnolence
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Headache
         subjects affected / exposed
    25 / 58 (43.10%)
         occurrences all number
    41
    Hypoaesthesia
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Paraesthesia
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Presyncope
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    10 / 58 (17.24%)
         occurrences all number
    10
    Thrombocytopenia
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Eye disorders
    Vision blurred
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    5
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    21 / 58 (36.21%)
         occurrences all number
    32
    Vomiting
         subjects affected / exposed
    17 / 58 (29.31%)
         occurrences all number
    22
    Nausea
         subjects affected / exposed
    17 / 58 (29.31%)
         occurrences all number
    27
    Constipation
         subjects affected / exposed
    10 / 58 (17.24%)
         occurrences all number
    13
    Abdominal pain
         subjects affected / exposed
    6 / 58 (10.34%)
         occurrences all number
    9
    Dyspepsia
         subjects affected / exposed
    6 / 58 (10.34%)
         occurrences all number
    7
    Abdominal pain upper
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    8
    Gastritis
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    4
    Haemorrhoids
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    6 / 58 (10.34%)
         occurrences all number
    6
    Dry Skin
         subjects affected / exposed
    6 / 58 (10.34%)
         occurrences all number
    6
    Rash
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    7
    Pruritus
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    8
    Renal and urinary disorders
    End stage renal disease
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Haematuria
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Acute kidney injury
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    4
    Dysuria
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    16 / 58 (27.59%)
         occurrences all number
    22
    Back pain
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    7
    Muscle spasms
         subjects affected / exposed
    6 / 58 (10.34%)
         occurrences all number
    6
    Pain in extremity
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    10
    Neck pain
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    12 / 58 (20.69%)
         occurrences all number
    25
    Nasopharyngitis
         subjects affected / exposed
    9 / 58 (15.52%)
         occurrences all number
    29
    Oral herpes
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Device related infection
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Gastroenteritis
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Rhinitis
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    5
    Cystitis
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    6
    Bronchitis
         subjects affected / exposed
    5 / 58 (8.62%)
         occurrences all number
    5
    Sinusitis
         subjects affected / exposed
    5 / 58 (8.62%)
         occurrences all number
    7
    Pneumonia
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    7
    Influenza
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 58 (10.34%)
         occurrences all number
    6
    Metabolism and nutrition disorders
    Hypokalaemia 
         subjects affected / exposed
    7 / 58 (12.07%)
         occurrences all number
    16
    Hypocalcaemia
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    3
    Vitamin D deficiency
         subjects affected / exposed
    3 / 58 (5.17%)
         occurrences all number
    4
    Decreased appetite
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4
    Iron deficiency
         subjects affected / exposed
    4 / 58 (6.90%)
         occurrences all number
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Sep 2016
    Ravulizumab loading and maintenance doses were lowered for all body weight groups.
    23 Jan 2017
    • Added clarification to primary endpoint description that participants must meet all Complete TMA Response criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. • Added clarification to secondary objectives (CKD stage as evaluated by eGFR; hemoglobin increase observed at 2 separate assessments obtained at least 4 weeks [28 days] apart, and any measurement in between). • Revised Exclusion Criteria 2 to allow administration of the first dose of study drug while awaiting the results of stool Shiga toxin test results. • Removed the requirement of systolic blood pressure ≤ 140 millimeters of mercury (mmHg) for at least 4 days. • Added benefit/risk assessment text. • Clarified withdrawal criteria to specify serious infusion reaction, severe uncontrolled infection, and pregnancy. • Minor corrections and clarifications were made to the schedule of assessments and language describing drug packaging, storage, and preparation; prior/concomitant medications/procedures; prohibited medications; vaccination; contraception; medical history; vital signs; immunogenicity; suspected unexpected serious adverse reaction (SUSAR) reporting, adverse events; pharmacokinetic (PK)/pharmacodyanamic (PD) assessment; genetics; statistical analysis; data monitoring committee (DMC); regulatory considerations; references; appendices.
    19 Jul 2017
    • Revised Inclusion Criteria to include platelet count, LDH, and hemoglobin laboratory results during the Screening Period or within 28 days prior to the start of the Screening Period from a local laboratory; these changes allow participants with recent plasma exchange/plasma infusion (which alters laboratory results) to enter the study based on laboratory results prior to plasma exchange/plasma infusion. • Continued to require that serum creatinine results for Inclusion Criterion must be based on central laboratory results from a specimen collected during the Screening Period. Since the primary endpoint is a change from baseline in creatinine, it is important to have both baseline and on-treatment serum samples from the same laboratory. • Provided clarification that eligibility may be determined using results from tests carried out as standard of care for the treatment of the current TMA prior to a participant giving informed consent, including tests noted in Exclusion Criteria. • Removed the requirement for culture/antigen test. • Clarified participants with genetic defects in vitamin B12 metabolism (a rare cause of HUS not related to complement), rather than a deficit in vitamin B12, were excluded. • Provided Sponsor opportunity to exclude participants on basis of risk to participant or impact on the interpretation of the efficacy or safety results for the study. • Added a requirement to have at least 30 participants enrolled who met all 4 TMA requirements at Day 1 (platelet count of < 150,000/microliter (μL), LDH ≥ 1.5 × upper limit of normal (ULN), hemoglobin ≤ lower limit of normal (LLN), and serum creatinine level ≥ ULN) to ensure that a majority of participants enrolled had abnormal baseline laboratory values. • Provided the option for serum pregnancy tests to be used at any time points. • Removed the option for “a designee” to perform the physical examination.
    19 Jul 2017
    • Added pregnancy test assessment prior to first dose in Extension Period; removed requirement for pregnancy test to use urine (serum may now be used at all indicated timepoints). • Clarified terminology on “meeting” vs “satisfying” inclusion and exclusion criteria and added option for the participant’s legally authorized representative to provide informed consent. • Corrected use of “assent” vs “consent”. • Clarified that there were separate tests for urine chemistry and urinalysis.
    07 May 2019
    • Increased duration of the Extension Period from 2 years to 4.5 years or until the product is registered or approved (in accordance with country-specific regulations), whichever occurs first, to allow additional safety, PK/PD, and immunogenicity evaluations. • Revised schedule of assessments to align with the increased duration of the Extension Period. • Information on discontinuation of participants was clarified by differentiating early termination of participants from study versus discontinuation of ravulizumab treatment with continuation in the study for monitoring visit. • Added criteria on TMA recurrence and guidance on retreatment with ravulizumab for participants who discontinue ravulizumab and remain in the study.

    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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