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    Clinical Trial Results:
    A Phase 3, Open-Label, Multicenter Study of ALXN1210 in Children and Adolescents With Atypical Hemolytic Uremic Syndrome (aHUS)

    Summary
    EudraCT number
    		 2016-002499-29
    Trial protocol
    		 GB   DE   AT   SE   ES   BE   IT   FR  
    Global end of trial date
    20 Dec 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    02 Jul 2023
    First version publication date
    16 Jul 2022
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    ALXN1210-aHUS-312
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03131219
    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)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001943-PIP01-16
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Mar 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Dec 2022
    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 efficacy of ravulizumab to control disease activity in children and adolescents with aHUS who have not previously used a complement inhibitor (complement inhibitor treatment-naïve), as well as in complement inhibitor-experienced (eculizumab-experienced) adolescent participants.
    Protection of trial subjects
    This trial was conducted in compliance with Good Clinical Practice.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Sep 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
    United States: 14
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Japan: 5
    Country: Number of subjects enrolled
    United Kingdom: 1
    Worldwide total number of subjects
    34
    EEA total number of subjects
    8
    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)
    7
    Children (2-11 years)
    17
    Adolescents (12-17 years)
    10
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This is an ongoing study and the data presented are the study results from the 26-week Initial Evaluation Period and data from the Extension Period through the data cutoff date at 03 Dec 2019.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Complement Inhibitor Treatment Naïve
    Arm description
    		 Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    ALXN1210
    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.

    Arm title
    		 Eculizumab Experienced
    Arm description
    		 Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    ALXN1210
    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
    		Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Started
    24
    10
    Received At Least 1 Dose of Study Drug
    24
    10
    Completed
    17
    10
    Not completed
    7
    0
         Physician decision
    1
    -
         Adverse event
    2
    -
         Deemed ineligible post treatment
    3
    -
         Protocol deviation
    1
    -
    Period 2
    Period 2 title
    Extension Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Complement Inhibitor Treatment Naïve
    Arm description
    		 Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    ALXN1210
    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.

    Arm title
    		 Eculizumab Experienced
    Arm description
    		 Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    ALXN1210
    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
    		Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Started
    17
    10
    Received At Least 1 Dose of Study Drug
    17
    10
    Completed
    16
    10
    Not completed
    1
    0
         Physician decision
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Complement Inhibitor Treatment Naïve
    Reporting group description
    		 Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.

    Reporting group title
    Eculizumab Experienced
    Reporting group description
    		 Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.

    Reporting group values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced Total
    Number of subjects
    		 24 10 34
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 6 1 7
        Children (2-11 years)
    		 15 2 17
        Adolescents (12-17 years)
    		 3 7 10
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 6.0 ( 4.79 ) 11.0 ( 4.97 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 14 1 15
        Male
    		 10 9 19
    Baseline Estimated Glomerular Filtration Rate (eGFR)
    Units: mL/min/1.73 m^2
        arithmetic mean (standard deviation)
    		 26.4 ( 21.17 ) 104.90 ( 29.545 ) -

    End points

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    End points reporting groups
    Reporting group title
    Complement Inhibitor Treatment Naïve
    Reporting group description
    		 Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.

    Reporting group title
    Eculizumab Experienced
    Reporting group description
    		 Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.
    Reporting group title
    Complement Inhibitor Treatment Naïve
    Reporting group description
    		 Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.

    Reporting group title
    Eculizumab Experienced
    Reporting group description
    		 Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.

    Primary: Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26

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    End point title
    		 Percentage Of Complement Inhibitor Treatment-naïve Participants With Complete Thrombotic Microangiopathy (TMA) Response at Week 26 [1] [2]
    End point description
    Complete TMA response during the 26-week Initial Evaluation Period is a composite endpoint that required normalization of hematological parameters (platelet count and lactate dehydrogenase) and improvement in kidney function (≥25% reduction in serum creatinine from baseline); for participants on dialysis, baseline was established at least 6 days after the end of dialysis. Participants had to meet these criteria for 2 separate assessments obtained at least 4 weeks apart, and any measurement in between. To be considered a responder, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment. Percentage based on the responders among treated participants. Full Analysis Set: 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'= those who were 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 analysis was planned to be reported for this endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be reported for "Complement Inhibitor Treatment Naïve" arm only.
    End point values
    		 Complement Inhibitor Treatment Naïve
    Number of subjects analysed
    18
    Units: percentage of participants
    number (confidence interval 95%)
        Complete TMA response
    77.8 (52.4 to 93.6)
        Platelet count normalization
    94.4 (72.7 to 99.9)
        LDH normalization
    88.9 (65.3 to 98.6)
        ≥25% improvement in serum creatinine from baseline
    83.3 (58.6 to 96.4)
    No statistical analyses for this end point

    Secondary: Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants

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    End point title
    		 Time To Complete TMA Response In Complement Inhibitor Treatment-naïve Participants [3]
    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. Participants had to meet all complete TMA response criteria at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. 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' signifies those who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline through at least Week 52 and up to Week 111
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be reported for "Complement Inhibitor Treatment Naïve" arm only.
    End point values
    		 Complement Inhibitor Treatment Naïve
    Number of subjects analysed
    18
    Units: days
        median (inter-quartile range (Q1-Q3))
    30.0 (22.0 to 88.0)
    No statistical analyses for this end point

    Secondary: Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response at Week 52

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    End point title
    		 Proportion Of Complement Inhibitor Treatment-naïve Participants With Complete TMA Response at Week 52 [4]
    End point description
    The proportion of participants considered responders, along with a 2-sided 95% CI based on exact confidence limits using the Clopper Pearson method 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' signifies those who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Week 52
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be reported for "Complement Inhibitor Treatment Naïve" arm only.
    End point values
    		 Complement Inhibitor Treatment Naïve
    Number of subjects analysed
    18
    Units: proportion of participants
    number (confidence interval 95%)
        Complete TMA responder
    0.882 (0.636 to 0.985)
        Platelet count normalization
    0.882 (0.636 to 0.985)
        LDH normalization
    1.000 (0.805 to 1.000)
        ≥25% improvement in serum creatinine from baseline
    1.000 (0.805 to 1.000)
    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' signifies those who were evaluable for this outcome measure and ‘Number Analyzed’ signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Week 26 and Week 52
    End point values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Number of subjects analysed
    6
    0 [5]
    Units: participants
        Week 26
    5
        Week 52
    6
    Notes
    [5] - No participants were analyzed for this reporting group.
    No statistical analyses for this end point

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

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    End point title
    		 Change From Baseline In eGFR At Weeks 26 and 52
    End point description
    Kidney function evaluated by eGFR was summarized at baseline and the Week 26 and Week 52 time points using descriptive statistics for continuous variables for the observed value, as well as the change from baseline. The baseline value was defined as the average of the values from the assessments performed prior to the first study drug infusion (these could include results from Screening and the Day 1 visit). A value of 10 mL/min/1.73 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. Analysis population was Full Analysis Set. Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure and ‘Number Analyzed’ signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Number of subjects analysed
    18
    10
    Units: mL/min/1.73 m^2
    median (full range (min-max))
        Baseline (n=17, 10)
    22.0 (10 to 84)
    99.75 (54 to 136.5)
        Change From Baseline at Week 26 (n=17, 10)
    80.0 (0 to 222)
    -2.00 (-94 to 18)
        Change From Baseline at Week 52 (n=16, 10)
    94.0 (10 to 230)
    -3.00 (-20 to 9)
    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 (classified based on the National Kidney Foundation CKD Stage) is presented as the change from baseline in the 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 the CKD stage at baseline. Baseline was derived based on the last available eGFR before starting treatment. Stage 5 was considered the worst category, while Stage 1 was considered the 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. Analysis population was Full Analysis Set. Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this endpoint and ‘Number Analyzed’ signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26, and Week 52
    End point values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Number of subjects analysed
    18
    10
    Units: participants
        Week 26, Improved (n=17, 10)
    15
    0
        Week 26, Worsened (n=17, 10)
    0
    3
        Week 26, Stayed the Same (n=17, 10)
    2
    7
        Week 52, Improved (n=16, 10)
    16
    0
        Week 52, Worsened (n=11, 10)
    0
    0
        Week 52, Stayed the Same (n=16, 10)
    0
    10
    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 time point (Week 26 or Week 52). Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this endpoint and ‘Number Analyzed’ signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Number of subjects analysed
    18
    10
    Units: platelets*10^9/L
    median (full range (min-max))
        Baseline (n=18, 10)
    51.25 (14 to 125)
    281.75 (207 to 415.5)
        Change from Baseline at Week 26 (n=18, 10)
    247.00 (57.5 to 368.5)
    -2.25 (-74.5 to 123.5)
        Change from Baseline at Week 52 (n=17, 10)
    213.00 (19.5 to 471.5)
    -34.75 (-109 to 109)
    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 serum. 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, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this endpoint and ‘Number Analyzed’ signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Number of subjects analysed
    18
    10
    Units: U/L
    median (full range (min-max))
        Baseline (n=17, 10)
    1963.00 (772 to 4985)
    206.50 (138.5 to 356)
        Change From Baseline at Week 26 (n=16, 10)
    -1851.50 (-4713 to -513)
    -8.50 (-50.5 to 50.5)
        Change From Baseline at Week 52 (n=16, 10)
    -1825.50 (-4724 to -579)
    -17.50 (-34.5 to 29.5)
    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 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 timepoint (Week 26 or Week 52). Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this endpoint and ‘Number Analyzed’ signifies participants evaluable for specified categories.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Number of subjects analysed
    18
    10
    Units: g/L
    median (full range (min-max))
        Baseline (n=18, 10)
    74.25 (32 to 106)
    132.00 (114.5 to 148)
        Change From Baseline at Week 26 (n=15, 10)
    46.50 (26.5 to 86)
    -3.50 (-19.5 to 8)
        Change From Baseline at Week 52 (n=17, 10)
    51.50 (-19 to 80)
    5.50 (-7.5 to 13.5)
    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 [6]
    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 (28 days) 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. The 95% CIs are based on exact confidence limits using the Clopper-Pearson method. 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). Analysis population was Full Analysis Set. Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Baseline through Week 26 and through Week 52
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint was planned to be reported for "Complement Inhibitor Treatment Naïve" arm only.
    End point values
    		 Complement Inhibitor Treatment Naïve
    Number of subjects analysed
    18
    Units: percentage of participants
    number (confidence interval 95%)
        Week 26
    100 (80.5 to 100)
        Week 52
    94.1 (71.3 to 99.9)
    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 (Participants ≥5 Years Of Age) 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 (Participants ≥5 Years Of Age) At Weeks 26 and 52
    End point description
    Quality of life was assessed in participants >5 years of age by the Pediatric FACIT-Fatigue Questionnaire (reported by participants who were ≥8 years of age at the time of enrollment; caregiver reported or caregiver assistance for participants who were 5 to <8 years of age at the time of enrollment). The FACIT Fatigue data were summarized at baseline and each post baseline time point using descriptive statistics for continuous variables for the observed value as well as the change from baseline. The FACIT Fatigue Version 4 questionnaire at baseline and each post-infusion time point was scored using standard scoring algorithms. The score ranges from 0 to 52, with a higher score indicating less fatigue. An increase in score indicated an improvement in quality of life. Analysis population was Full Analysis Set. Here, Overall 'Number of Participants Analyzed' signifies those who were evaluable for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 26 and Week 52
    End point values
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Number of subjects analysed
    9
    8
    Units: units on a scale
    median (full range (min-max))
        Baseline
    35.00 (4 to 44)
    50.00 (42 to 52)
        Change From Baseline at Week 26
    10.00 (4 to 48)
    0.00 (-5 to 3)
        Change From Baseline at Week 52
    9.00 (3 to 47)
    -1.00 (-7 to 2)
    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 (Day 1) through data cutoff (at least 52 weeks and up to a maximum of 111 weeks of treatment, representing 36.2 patient-years of exposure).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Complement Inhibitor Treatment Naïve
    Reporting group description
    		 Complement inhibitor treatment-naïve participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.

    Reporting group title
    Eculizumab Experienced
    Reporting group description
    		 Eculizumab-experienced participants received weight-based doses of ravulizumab during the 26-week Initial Evaluation Period. After the Initial Evaluation Period, participants rolled over into an Extension Period in which all participants continued their weight-based maintenance dose of ravulizumab.

    Serious adverse events
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 24 (66.67%)
    1 / 10 (10.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    4 / 24 (16.67%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Glomerulonephritis membranoproliferative
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Juvenile idiopathic arthritis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus enteritis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia pyelonephritis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Human bocavirus infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral pharyngitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 10 (10.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Complement Inhibitor Treatment Naïve Eculizumab Experienced
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 24 (91.67%)
    10 / 10 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic naevus
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 24 (25.00%)
    1 / 10 (10.00%)
         occurrences all number
    7
    1
    Hypotension
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Hot flush
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    12 / 24 (50.00%)
    1 / 10 (10.00%)
         occurrences all number
    25
    1
    Fatigue
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 10 (10.00%)
         occurrences all number
    3
    1
    Oedema
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Device related thrombosis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Vascular device occlusion
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Dysplasia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Face oedema
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Peripheral swelling
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Vaccination site reaction
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Chills
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    Reproductive system and breast disorders
    Penile erythema
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Sinus disorder
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    Epistaxis
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 10 (20.00%)
         occurrences all number
    5
    2
    Oropharyngeal pain
         subjects affected / exposed
    2 / 24 (8.33%)
    3 / 10 (30.00%)
         occurrences all number
    3
    3
    Productive cough
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Dyspnoea
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Nasal congestion
         subjects affected / exposed
    4 / 24 (16.67%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    Rhinorrhoea
         subjects affected / exposed
    4 / 24 (16.67%)
    0 / 10 (0.00%)
         occurrences all number
    7
    0
    Cough
         subjects affected / exposed
    5 / 24 (20.83%)
    2 / 10 (20.00%)
         occurrences all number
    10
    2
    Wheezing
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Bronchospasm
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pharyngeal erythema
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pulmonary oedema
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pleural effusion
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Tachypnoea
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Depressed mood
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Attention deficit hyperactivity disorder
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Device malfunction
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Influenza A virus test positive
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Vitamin D decreased
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences all number
    5
    0
    Clostridium test positive
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Amylase increased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Salmonella test positive
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    White blood cell count increased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Blood iron decreased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Blood potassium increased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Crystal urine present
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Transaminases increased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    White blood cell count decreased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    6
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    5 / 24 (20.83%)
    1 / 10 (10.00%)
         occurrences all number
    10
    1
    Head injury
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Skin abrasion
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Ligament sprain
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Arthropod sting
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    Limb injury
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Eye injury
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Radial head dislocation
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Thermal burn
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Torus fracture
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Wound
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Lip injury
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Scratch
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Traumatic haematoma
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Cardiac disorders
    Cardiomegaly
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Left ventricular hypertrophy
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Angina pectoris
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Tachycardia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    8 / 24 (33.33%)
    1 / 10 (10.00%)
         occurrences all number
    26
    1
    Dizziness
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Central nervous system lesion
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Seizure
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Cerebral disorder
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Lethargy
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 10 (10.00%)
         occurrences all number
    2
    1
    Anaemia
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences all number
    6
    0
    Neutropenia
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Macrocytosis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Increased tendency to bruise
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    External ear inflammation
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Photophobia
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Lacrimation increased
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Eye discharge
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Amblyopia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hypermetropia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Periorbital oedema
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Strabismus
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Conjunctival oedema
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Eye pain
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Ocular hyperaemia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    8 / 24 (33.33%)
    2 / 10 (20.00%)
         occurrences all number
    30
    3
    Dyspepsia
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 10 (10.00%)
         occurrences all number
    3
    1
    Diarrhoea
         subjects affected / exposed
    7 / 24 (29.17%)
    2 / 10 (20.00%)
         occurrences all number
    14
    2
    Abdominal pain
         subjects affected / exposed
    5 / 24 (20.83%)
    1 / 10 (10.00%)
         occurrences all number
    10
    1
    Abdominal distension
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Nausea
         subjects affected / exposed
    4 / 24 (16.67%)
    0 / 10 (0.00%)
         occurrences all number
    12
    0
    Constipation
         subjects affected / exposed
    5 / 24 (20.83%)
    0 / 10 (0.00%)
         occurrences all number
    9
    0
    Pancreatitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorder
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Acetonaemic vomiting
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Breath odour
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Gingival bleeding
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Mouth haemorrhage
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Rectal prolapse
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Duodenal ulcer
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Faecaloma
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Gastric ulcer
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Odynophagia
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    Lip dry
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Tooth disorder
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Dermatitis diaper
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Rash
         subjects affected / exposed
    4 / 24 (16.67%)
    0 / 10 (0.00%)
         occurrences all number
    5
    0
    Erythema
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Asteatosis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Dry skin
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    5
    0
    Skin exfoliation
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Alopecia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Dermatitis contact
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Keratosis pilaris
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Scab
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Skin hypopigmentation
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Erythema multiforme
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Nail discolouration
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Rash papular
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Miliaria
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Chronic kidney disease
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hydronephrosis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Proteinuria
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Haematuria
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Tenosynovitis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 10 (10.00%)
         occurrences all number
    2
    2
    Osteochondrosis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    3 / 24 (12.50%)
    1 / 10 (10.00%)
         occurrences all number
    4
    1
    Myalgia
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences all number
    7
    0
    Arthralgia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Mobility decreased
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Juvenile idiopathic arthritis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Osteopenia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Tendonitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Otitis media
         subjects affected / exposed
    1 / 24 (4.17%)
    2 / 10 (20.00%)
         occurrences all number
    1
    3
    Pharyngitis
         subjects affected / exposed
    2 / 24 (8.33%)
    3 / 10 (30.00%)
         occurrences all number
    2
    3
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 24 (16.67%)
    4 / 10 (40.00%)
         occurrences all number
    6
    23
    Viral infection
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    Pneumonia
         subjects affected / exposed
    2 / 24 (8.33%)
    1 / 10 (10.00%)
         occurrences all number
    2
    1
    Influenza
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 10 (10.00%)
         occurrences all number
    1
    1
    Impetigo
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Hand-foot-and-mouth disease
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    2
    Bronchitis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    4
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 10 (20.00%)
         occurrences all number
    5
    3
    Nasopharyngitis
         subjects affected / exposed
    7 / 24 (29.17%)
    2 / 10 (20.00%)
         occurrences all number
    14
    2
    Sinusitis
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Conjunctivitis
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Tonsilitis
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences all number
    4
    0
    Rhinovirus infection
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    5
    0
    Otitis externa
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Gastroenteritis
         subjects affected / exposed
    2 / 24 (8.33%)
    2 / 10 (20.00%)
         occurrences all number
    2
    2
    COVID-19
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 24 (4.17%)
    1 / 10 (10.00%)
         occurrences all number
    4
    1
    Oral herpes
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Ear infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Body tinea
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Skin infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Vaginal infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Enterobiasis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Molluscum contagiosum
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Myringitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Cellulitis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Cytomegalovirus enteritis
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Soft tissue infection
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Croup infectious
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    2
    2
    Onychomycosis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Tinea pedis
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 24 (4.17%)
    2 / 10 (20.00%)
         occurrences all number
    4
    2
    Iron deficiency
         subjects affected / exposed
    3 / 24 (12.50%)
    0 / 10 (0.00%)
         occurrences all number
    3
    0
    Decreased appetite
         subjects affected / exposed
    2 / 24 (8.33%)
    0 / 10 (0.00%)
         occurrences all number
    2
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0
    Underweight
         subjects affected / exposed
    0 / 24 (0.00%)
    1 / 10 (10.00%)
         occurrences all number
    0
    1
    Acetonaemia
         subjects affected / exposed
    1 / 24 (4.17%)
    0 / 10 (0.00%)
         occurrences all number
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Aug 2018
    •The loading dose for patients 5 to < 10 kg was increased from 300 milligrams (mg) to 600 mg. •The entry criteria were revised to allow enrollment into Cohort 2 of adolescent participants previously treated with eculizumab for at least the past 90 days. •Revised the entry criterion to allow LDH and hemoglobin results obtained during the Screening Period or within 28 days prior to the start of the Screening Period. •New objectives and endpoints were added to evaluate the safety and efficacy of ALXN1210 in Cohort 2. •Added 2 interim analyses: 1) when 12 to 14 complement inhibitor treatment-naïve participants (i.e., Cohort 1) have completed or withdrawn from the end of the 26-week Initial Evaluation Period; and 2) when all study participants have completed or withdrawn from the 26-week Initial Evaluation Period. •The Screening Period was clarified as 28 days for Cohort 2. •Added a provision to allow a supplemental dose of ALXN1210 to be administered to a participant if the Investigator and Sponsor mutually agree that a participant will potentially benefit. •Added a provision to allow for a dose to be administered as 2 separate infusions no more than approximately 24 hours apart if the Investigator and Sponsor mutually agree that the infusion volume (120 mL) of the loading dose for patients ≥ 5 to < 10 kg (600 mg) was too high for an individual participant. •The study sample size was increased to align with the planned sample size for each age category. • Statistical language was clarified to indicate that the analyses for Cohort 1 and Cohort 2 would be conducted and reported separately. •To reduce the participant data collection burden, removed the exploratory endpoints of Additional Signs or Symptoms of aHUS and Healthcare Resource Utilization.
    16 Jul 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, pharmacokinetic/pharmacodynamic (PK/PD), and immunogenicity evaluations. •Revised schedule of assessments to align with the increased duration of the Extension Period. •To improve clarity, to differentiate early termination of participants from study versus discontinuation of ravulizumab treatment with continuation in the study (for monitoring visits) in the Extension Period. •Added criteria on TMA recurrence and guidance on retreatment with ravulizumab for participants who discontinue ravulizumab and remain in the study in the Extension Period. •Expanded secondary efficacy and PK/PD endpoints to include evaluation of participants who discontinue study drug as well as those who resume treatment. •The language in the Data Monitoring Committee was aligned with other protocols at a program level.

    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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