Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43440   clinical trials with a EudraCT protocol, of which   7185   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 3, Randomized, Open Label, Active Controlled Study of ALXN1210 Versus Eculizumab in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Eculizumab

    Summary
    EudraCT number
    		 2016-002026-36
    Trial protocol
    		 GB   DE   ES   NL   IT  
    Global end of trial date
    08 Apr 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    30 Mar 2023
    First version publication date
    08 Jul 2020
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALXN1210 PNH 302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    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
    lexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 7 87148158, clinicaltrials.eu@alexion.com
    Scientific contact
    Alexion Europe SAS European Clinical Trial Information, Alexion Pharmaceuticals Inc., +33 7 87148158, 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
    31 Mar 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Mar 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Apr 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary purpose of this study was to assess the noninferiority of ravulizumab compared to eculizumab in adult patients with PNH who were clinically stable after having been treated with eculizumab for at least the past 6 months.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonisation (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the countries in which the study was conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    05 Jun 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 4 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 10
    Country: Number of subjects enrolled
    Canada: 10
    Country: Number of subjects enrolled
    France: 29
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Italy: 15
    Country: Number of subjects enrolled
    Japan: 13
    Country: Number of subjects enrolled
    Netherlands: 11
    Country: Number of subjects enrolled
    Korea, Republic of: 20
    Country: Number of subjects enrolled
    Spain: 19
    Country: Number of subjects enrolled
    United Kingdom: 44
    Country: Number of subjects enrolled
    United States: 14
    Worldwide total number of subjects
    195
    EEA total number of subjects
    84
    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)
    165
    From 65 to 84 years
    30
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Participants were stratified into 1 of 2 groups based on their transfusion history. Stratified participants were randomly assigned in a 1:1 ratio to receive ravulizumab or eculizumab. Participants in the full analysis set (FAS) were also reported.

    Period 1
    Period 1 title
    Primary Evaluation Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ravulizumab/Ravulizumab
    Arm description
    		 On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Arm title
    		 Eculizumab/Ravulizumab
    Arm description
    		 Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Number of subjects in period 1
    		Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Started
    97
    98
    Received at least 1 dose of study drug
    97
    98
    Participants in the FAS
    97
    98
    Completed
    96
    95
    Not completed
    1
    3
         Consent withdrawn by subject
    1
    1
         Pregnancy
    -
    1
         Lack of efficacy
    -
    1
    Period 2
    Period 2 title
    Extension Period
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ravulizumab/Ravulizumab
    Arm description
    		 On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ravulizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Arm title
    		 Eculizumab/Ravulizumab
    Arm description
    		 Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eculizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26- week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Number of subjects in period 2
    		Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Started
    96
    95
    Completed
    92
    88
    Not completed
    4
    7
         Adverse event, serious fatal
    -
    3
         Physician decision
    3
    3
         Consent withdrawn by subject
    1
    -
         Lost to follow-up
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ravulizumab/Ravulizumab
    Reporting group description
    		 On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Reporting group title
    Eculizumab/Ravulizumab
    Reporting group description
    		 Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Reporting group values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab Total
    Number of subjects
    		 97 98 195
    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)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 84 81 165
        From 65-84 years
    		 13 17 30
        85 years and over
    		 0 0 0
    Age Continuous
    Age at first infusion of study drug
    Units: years
        arithmetic mean (standard deviation)
    		 46.6 ± 14.41 48.8 ± 13.97 -
    Sex: Female, Male
    Units: participants
        Female
    		 47 50 97
        Male
    		 50 48 98
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 3 4 7
        Not Hispanic or Latino
    		 76 77 153
        Unknown or Not Reported
    		 18 17 35
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 50 61 111
        Asian
    		 23 19 42
        Not Reported
    		 13 13 26
        Black or African American
    		 5 3 8
        Unknown
    		 3 1 4
        Other
    		 2 1 3
        Multiple
    		 1 0 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Ravulizumab/Ravulizumab
    Reporting group description
    		 On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Reporting group title
    Eculizumab/Ravulizumab
    Reporting group description
    		 Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.
    Reporting group title
    Ravulizumab/Ravulizumab
    Reporting group description
    		 On Day 1, participants received weight-based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Reporting group title
    Eculizumab/Ravulizumab
    Reporting group description
    		 Participants received 900 mg of eculizumab every 2 weeks (q2w) for 26 weeks. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Primary: Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183

    		 Close Top of page
    End point title
    		 Percent Change In Lactate Dehydrogenase Levels From Baseline To Day 183
    End point description
    Lactate dehydrogenase (LDH) is an indicator of intravascular hemolysis that occurs in participants with paroxysmal nocturnal hemoglobinuria. A decrease in LDH indicates reduction (improvement) in hemolysis. Baseline was defined as the average of all available on-study assessments prior to the first study drug infusion. The percent change in LDH was analyzed using a mixed-effect model for repeated measures (MMRM) with the fixed, categorical effects of treatment, study visit, and study visit by treatment group interaction, as well as the continuous, fixed covariate of baseline LDH and the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1).
    End point type
    Primary
    End point timeframe
    Baseline, Day 183
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    97
    98
    Units: percent change
        least squares mean (confidence interval 95%)
    -0.82 (-7.75 to 6.11)
    8.39 (1.47 to 15.32)
    Statistical analysis title
    		 Percent Change In Lactate Dehydrogenase Level
    Statistical analysis description
    Adjusting for a possible 10% dropout rate, a minimum of 192 participants were estimated to provide 90% power to demonstrate noninferiority of ravulizumab to eculizumab.
    Comparison groups
    Ravulizumab/Ravulizumab v Eculizumab/Ravulizumab
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    -9.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.84
         upper limit
    		 0.42
    Notes
    [1] - A difference in percent change in LDH between the ravulizumab and eculizumab treatment groups at Day 183 along with a 2-sided 95% confidence interval (CI) was calculated. Noninferiority margin (NIM) was based on the upper bound of the 95% CI. NIM was 15%.

    Secondary: Number Of Participants With Breakthrough Hemolysis Through Day 183

    		 Close Top of page
    End point title
    		 Number Of Participants With Breakthrough Hemolysis Through Day 183
    End point description
    Breakthrough hemolysis (BTH) was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin <10 grams (g)/deciliter (dL)], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times the upper limit of normal (ULN).
    End point type
    Secondary
    End point timeframe
    Baseline through Day 183
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    97
    98
    Units: number of participants
        number (confidence interval 95%)
    0 (0.00 to 3.73)
    5 (1.68 to 11.51)
    Statistical analysis title
    		 Number of Participants with Breakthrough Hemolysis
    Statistical analysis description
    A difference in the percentages of participants with BTH was calculated between the ravulizumab and eculizumab treatment groups, along with a 95% CI for the difference using the stratified Newcombe CI method. The stratification factor observed was transfusion history within 1 year prior to first dose of study drug.
    Comparison groups
    Ravulizumab/Ravulizumab v Eculizumab/Ravulizumab
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [2]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    -5.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.99
         upper limit
    		 8.89
    Notes
    [2] - NIM was based on the upper bound of the 95% CI. NIM was 20%.

    Secondary: Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores

    		 Close Top of page
    End point title
    		 Change From Baseline To Day 183 In Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Scores
    End point description
    FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline was defined as the last non-missing assessment value prior to first study drug dose. Change in FACIT-Fatigue score from Baseline to Day 183 was analyzed using an MMRM with the fixed, categorical effects of treatment, the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1), study visit, and study visit by treatment group interaction, as well as the continuous fixed covariate of Baseline FACIT-Fatigue score.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 183
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    97
    98
    Units: units on a scale
        least squares mean (confidence interval 95%)
    2.01 (0.64 to 3.39)
    0.54 (-0.84 to 1.93)
    Statistical analysis title
    		 Change from Baseline in FACIT-Fatigue Scores
    Comparison groups
    Ravulizumab/Ravulizumab v Eculizumab/Ravulizumab
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [3]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    1.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 3.15
    Notes
    [3] - NIM was based on the lower bound of the 95% CI. NIM margin was -3.

    Secondary: Percentage Of Participants Who Achieved Transfusion Avoidance Through Day 183

    		 Close Top of page
    End point title
    		 Percentage Of Participants Who Achieved Transfusion Avoidance Through Day 183
    End point description
    Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines (hemoglobin value of ≤9 g/dL with signs or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin value of ≤7 g/dL regardless of presence of clinical signs or symptoms) through Day 183.
    End point type
    Secondary
    End point timeframe
    Baseline through Day 183
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    97
    98
    Units: percentage of participants
        number (confidence interval 95%)
    87.6 (81.08 to 94.18)
    82.7 (75.16 to 90.15)
    Statistical analysis title
    		 Participants with Transfusion Avoidance
    Statistical analysis description
    A difference in the percentages of participants achieving transfusion avoidance was calculated between the ravulizumab and eculizumab treatment groups, along with a 95% CI for the difference using the stratified Newcombe CI method. The stratification factor observed was transfusion history within 1 year prior to first dose of study drug
    Comparison groups
    Ravulizumab/Ravulizumab v Eculizumab/Ravulizumab
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [4]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    5.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.27
         upper limit
    		 15.68
    Notes
    [4] - NIM was based on the lower bound of the 95% CI. NIM was -20%.

    Secondary: Percentage Of Participants With Stabilized Hemoglobin Levels Through Day 183

    		 Close Top of page
    End point title
    		 Percentage Of Participants With Stabilized Hemoglobin Levels Through Day 183
    End point description
    Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline in the absence of transfusion through Day 183.
    End point type
    Secondary
    End point timeframe
    Baseline through Day 183
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    97
    98
    Units: percentage of participants
        number (confidence interval 95%)
    76.3 (67.82 to 84.75)
    75.5 (67.00 to 84.02)
    Statistical analysis title
    		 Participants with Stabilized Hemoglobin Levels
    Statistical analysis description
    A difference in the percentages of participants with stabilized hemoglobin was calculated between the ravulizumab and eculizumab treatment groups, along with a 95% CI for the difference using the stratified Newcombe CI method. The stratification factor observed was transfusion history within 1 year prior to first dose of study drug.
    Comparison groups
    Ravulizumab/Ravulizumab v Eculizumab/Ravulizumab
    Number of subjects included in analysis
    195
    Analysis specification
    Pre-specified
    Analysis type
    		 [5]
    Method
    Parameter type
    		 Treatment Difference
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.41
         upper limit
    		 13.31
    Notes
    [5] - NIM was based on the lower bound of the 95% CI. NIM was -20%.

    Secondary: Number Of Participants With Breakthrough Hemolysis Through End of Study

    		 Close Top of page
    End point title
    		 Number Of Participants With Breakthrough Hemolysis Through End of Study
    End point description
    BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin <10 g/dL], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2 times the ULN.
    End point type
    Secondary
    End point timeframe
    Baseline through end of study (up to 5 years)
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    96
    95
    Units: number of participants
        number (confidence interval 95%)
    9 (4.38 to 17.05)
    6 (2.35 to 13.24)
    No statistical analyses for this end point

    Secondary: Change From Baseline To End of Study In FACIT-Fatigue Scores Through End of Study

    		 Close Top of page
    End point title
    		 Change From Baseline To End of Study In FACIT-Fatigue Scores Through End of Study
    End point description
    FACIT-Fatigue score ranges from 0 to 52, with a higher score indicating less fatigue. Baseline was defined as the last non-missing assessment value prior to first study drug dose. Change in FACIT-Fatigue score from Baseline to Day 183 was analyzed using an MMRM with the fixed, categorical effects of treatment, the stratification randomization indicator of packed red blood cells transfusion history (yes/no within 12 months prior to Day 1), study visit, and study visit by treatment group interaction, as well as the continuous fixed covariate of Baseline FACIT-Fatigue score.
    End point type
    Secondary
    End point timeframe
    Baseline, End of Study (up to 5 years)
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    14
    13
    Units: units on a scale
        arithmetic mean (standard deviation)
    -1.43 ± 5.694
    0.00 ± 5.944
    No statistical analyses for this end point

    Secondary: Percentage Of Participants Who Achieved Transfusion Avoidance Through End of Study

    		 Close Top of page
    End point title
    		 Percentage Of Participants Who Achieved Transfusion Avoidance Through End of Study
    End point description
    Transfusion avoidance was defined as the percentage of participants who remained transfusion free and did not require a transfusion per protocol-specified guidelines (hemoglobin value of ≤9 g/dL with signs or symptoms of sufficient severity to warrant a transfusion, or a hemoglobin value of ≤7 g/dL regardless of presence of clinical signs or symptoms) through the end of study.
    End point type
    Secondary
    End point timeframe
    Baseline through end of study (up to 5 years)
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    96
    95
    Units: percentage of participants
        number (confidence interval 95%)
    70.83 (60.67 to 79.67)
    70.53 (60.29 to 79.44)
    No statistical analyses for this end point

    Secondary: Percentage Of Participants With Stabilized Hemoglobin Levels Through End of Study

    		 Close Top of page
    End point title
    		 Percentage Of Participants With Stabilized Hemoglobin Levels Through End of Study
    End point description
    Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from Baseline in the absence of transfusion through end of study.
    End point type
    Secondary
    End point timeframe
    Baseline through end of study (up to 5 years)
    End point values
    		 Ravulizumab/Ravulizumab Eculizumab/Ravulizumab
    Number of subjects analysed
    96
    95
    Units: percentage of participants
        number (confidence interval 95%)
    58.33 (47.82 to 68.32)
    67.37 (59.68 to 76.64)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From Baseline (after first dose) to end of study (up to 5 years)
    Adverse event reporting additional description
    Ravulizumab arm: data for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events are for participants in the Ravulizumab-Treated Set. Eculizumab arm: data for All-Cause Mortality, Serious Adverse Events, and Other Adverse Events are for the participants in the Safety Set.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Ravulizumab
    Reporting group description
    		 On Day 1, participants received weight- based doses of ravulizumab ranging from 2400 to 3000 mg. Thereafter, weight- based doses of ravulizumab ranging from 3000 to 3600 mg were administered on Days 15, 71, and 127. After completion of the 26-week Primary Evaluation Period, participants had the opportunity to enter the Extension Period, wherein participants received weight-based doses of ravulizumab for up to 4 years.

    Reporting group title
    Eculizumab
    Reporting group description
    		 Participants received 900 mg of eculizumab q2w for 26 weeks.

    Serious adverse events
    		 Ravulizumab Eculizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    60 / 192 (31.25%)
    8 / 98 (8.16%)
         number of deaths (all causes)
    3
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Endometrial cancer
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive papillary breast carcinoma
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cancer metastatic
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Hyperthermia
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 192 (2.60%)
    3 / 98 (3.06%)
         occurrences causally related to treatment / all
    2 / 6
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Major depression
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Liver function test increased
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Transfusion reaction
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ligament injury
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrospinal fluid retention
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (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
    Haemolysis
         subjects affected / exposed
    5 / 192 (2.60%)
    2 / 98 (2.04%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Breakthrough haemolysis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aplastic anaemia
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    3 / 192 (1.56%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Toothache
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumoperitoneum
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 192 (0.52%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    2 / 192 (1.04%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary colic
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver disorder
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermal cyst
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (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
    Ureterolithiasis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc degeneration
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dupuytren's contracture
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (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
    Pyelonephritis acute
         subjects affected / exposed
    0 / 192 (0.00%)
    1 / 98 (1.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    5 / 192 (2.60%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 192 (1.56%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 192 (1.04%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 192 (1.04%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    2 / 192 (1.04%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumococcal infection
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Suspected COVID-19
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 192 (0.52%)
    0 / 98 (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: 5%
    Non-serious adverse events
    		 Ravulizumab Eculizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    175 / 192 (91.15%)
    85 / 98 (86.73%)
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    10 / 192 (5.21%)
    0 / 98 (0.00%)
         occurrences all number
    12
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    26 / 192 (13.54%)
    7 / 98 (7.14%)
         occurrences all number
    30
    8
    Headache
         subjects affected / exposed
    60 / 192 (31.25%)
    17 / 98 (17.35%)
         occurrences all number
    94
    26
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    16 / 192 (8.33%)
    3 / 98 (3.06%)
         occurrences all number
    22
    4
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    12 / 192 (6.25%)
    9 / 98 (9.18%)
         occurrences all number
    15
    12
    Fatigue
         subjects affected / exposed
    41 / 192 (21.35%)
    6 / 98 (6.12%)
         occurrences all number
    87
    8
    Pyrexia
         subjects affected / exposed
    40 / 192 (20.83%)
    2 / 98 (2.04%)
         occurrences all number
    61
    4
    Influenza like illness
         subjects affected / exposed
    21 / 192 (10.94%)
    8 / 98 (8.16%)
         occurrences all number
    45
    10
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    15 / 192 (7.81%)
    4 / 98 (4.08%)
         occurrences all number
    18
    4
    Nausea
         subjects affected / exposed
    35 / 192 (18.23%)
    9 / 98 (9.18%)
         occurrences all number
    43
    9
    Diarrhoea
         subjects affected / exposed
    36 / 192 (18.75%)
    7 / 98 (7.14%)
         occurrences all number
    50
    7
    Constipation
         subjects affected / exposed
    13 / 192 (6.77%)
    5 / 98 (5.10%)
         occurrences all number
    14
    6
    Abdominal pain
         subjects affected / exposed
    29 / 192 (15.10%)
    9 / 98 (9.18%)
         occurrences all number
    41
    9
    Abdominal pain upper
         subjects affected / exposed
    16 / 192 (8.33%)
    0 / 98 (0.00%)
         occurrences all number
    19
    0
    Dysphagia
         subjects affected / exposed
    11 / 192 (5.73%)
    0 / 98 (0.00%)
         occurrences all number
    12
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    32 / 192 (16.67%)
    10 / 98 (10.20%)
         occurrences all number
    43
    11
    Dyspnoea
         subjects affected / exposed
    16 / 192 (8.33%)
    6 / 98 (6.12%)
         occurrences all number
    26
    8
    Oropharyngeal pain
         subjects affected / exposed
    20 / 192 (10.42%)
    9 / 98 (9.18%)
         occurrences all number
    25
    9
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    10 / 192 (5.21%)
    0 / 98 (0.00%)
         occurrences all number
    12
    0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    0 / 192 (0.00%)
    5 / 98 (5.10%)
         occurrences all number
    0
    5
    Pain in extremity
         subjects affected / exposed
    24 / 192 (12.50%)
    4 / 98 (4.08%)
         occurrences all number
    28
    6
    Back pain
         subjects affected / exposed
    26 / 192 (13.54%)
    0 / 98 (0.00%)
         occurrences all number
    34
    0
    Arthralgia
         subjects affected / exposed
    22 / 192 (11.46%)
    0 / 98 (0.00%)
         occurrences all number
    26
    0
    Myalgia
         subjects affected / exposed
    10 / 192 (5.21%)
    0 / 98 (0.00%)
         occurrences all number
    17
    0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    53 / 192 (27.60%)
    10 / 98 (10.20%)
         occurrences all number
    79
    13
    Rhinitis
         subjects affected / exposed
    19 / 192 (9.90%)
    4 / 98 (4.08%)
         occurrences all number
    32
    5
    Nasopharyngitis
         subjects affected / exposed
    58 / 192 (30.21%)
    20 / 98 (20.41%)
         occurrences all number
    96
    21
    Gastroenteritis
         subjects affected / exposed
    11 / 192 (5.73%)
    0 / 98 (0.00%)
         occurrences all number
    15
    0
    Influenza
         subjects affected / exposed
    14 / 192 (7.29%)
    0 / 98 (0.00%)
         occurrences all number
    15
    0
    Urinary tract infection
         subjects affected / exposed
    16 / 192 (8.33%)
    0 / 98 (0.00%)
         occurrences all number
    31
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Oct 2017
    - Revised the statistical analysis description regarding control of Type I error when testing the primary and secondary end points for noninferiority and superiority. - Clarified that the last recorded study visit body weight should be used for determination of weight-based dose, and if study drug is prepared the night before a visit, the weight from the most recent study visit should be used. - Indicated the maximum permitted duration of an eculizumab infusion. - In order to reduce the incidence of ex vivo hemolyzed blood samples, it was specified that draws should not be made via a heparinized tube. - To reduce the participant data collection burden, removed the exploratory end points of Patient-Reported PNH Symptoms and Healthcare Resource Utilization, their description, and the questionnaires. - Clarified that participants who have home visits during the extension phase must return to the study site for any visit at which an abbreviated physical examination is required, as specified in the Schedule of Assessments.
    01 Mar 2019
    • Prolonged Extension Period from 2 years to 3 years and revised Schedule of Assessments.

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

    European Medicines Agency © 1995-2023 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA