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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Cross-Over, Multi-Center Study of Eculizumab in Patients with Generalized Myasthenia Gravis (gMG) Who Have Moderate to Severe Muscle Weakness Despite Treatment with Immunosuppressants.

    Summary
    EudraCT number
    		 2009-014669-13
    Trial protocol
    		 GB  
    Global end of trial date
    16 Mar 2011

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Jan 2017
    First version publication date
    06 Jan 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    C08-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Alexion Pharmaceuticals Incorporated
    Sponsor organisation address
    100 College Street , New Haven, CT, United States, 06510
    Public contact
    European Clinical Trial Information, Alexion Europe SAS, +33 1 47 10 06 06, clinicaltrials.eu@alexion.com
    Scientific contact
    European Clinical Trial Information, Alexion Europe SAS, +33 1 47 10 06 06, 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
    16 Mar 2011
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Mar 2011
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of this study is to determine whether eculizumab is safe and effective in the treatment of patients with generalized myasthenia gravis despite treatment with various immunosuppressants, such as prednisone, methotrexate, Cellcept, cyclosporine, and cyclophosphamide, that are currently available.
    Protection of trial subjects
    Patients must have been vaccinated for N meningitides 14 days prior to randomization at Visit 1 or during the observation period, as determined by the principal investigator's discretion.
    Background therapy
    		 Patients may continue on their MG medications, IST and/or cholinesterase inhibitor but must be on a stable dose prior and during the study.
    Evidence for comparator
    		 This was a Randomized, Double-Blind, Placebo-Controlled, Cross-Over, Multi-Center Study of Eculizumab in Patients with Generalized Myasthenia Gravis (gMG) who have Moderate to Severe Muscle Weakness Despite Treatment with Immunosuppressants. All patients received the treatment.
    Actual start date of recruitment
    01 Oct 2008
    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: 13
    Country: Number of subjects enrolled
    United Kingdom: 1
    Worldwide total number of subjects
    14
    EEA total number of subjects
    1
    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)
    11
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Patients received standard of care during the Screening Period. Patients were randomized to a treatment sequence to receive eculizumab in Period 1 followed by placebo in Period 2 or placebo in Period 1 followed by eculizumab in Period 2. Patients were permitted to continue on background immunosuppressive therapy throughout the study.

    Period 1
    Period 1 title
    Treatment Period 1
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst, Carer, Assessor
    Blinding implementation details
    Patients were centrally randomized via Almac Clinical Service’s secure web-based randomization application, WebEZ. The randomization code was maintained by Almac Clinical Services.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Eculizumab period 1
    Arm description
    		 Patients received eculizumab 600 mg via IVinfusion over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by 900 mg eculizumab via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    eculizumab
    Investigational medicinal product code
    Other name
    soliris
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 dose of 600mg weekly for 4 weeks, 900 mg for the fifth week. And 900 mg every two weeks for 6 doses

    Arm title
    		 Placebo period 1
    Arm description
    		 Patients received placebo via IV infusion... more over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by matching placebo via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Matching placebo
    Investigational medicinal product code
    placebo
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 dose weekly for 4 weeks than 1 dose for the fifth week and 1 doses every two weeks for 6 doses

    Number of subjects in period 1
    		Eculizumab period 1 Placebo period 1
    Started
    7
    7
    Completed
    7
    7
    Period 2
    Period 2 title
    Treatment Period 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Eculizumab period 2
    Arm description
    		 All these patients received placebo during period 1 During Period 2: Patients received eculizumab 600 mg via IV infusion over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by 900 mg eculizumab via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    eculizumab
    Investigational medicinal product code
    Other name
    soliris
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 dose of 600mg weekly for 4 weeks, 900 mg for the fifth week. And 900 mg every two week for 6 doses

    Arm title
    		 Placebo period 2
    Arm description
    		 All these patients received eculizumab during period 1 During period 2: Patients received placebo via IV infusion... more over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by matching placebo via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Matching placebo
    Investigational medicinal product code
    placebo
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    1 dose weekly for 4 weeks than 1 dose for the fifth week and 1 doses every two weeks for 6 doses

    Number of subjects in period 2 [1]
    		Eculizumab period 2 Placebo period 2
    Started
    6
    6
    Completed
    6
    5
    Not completed
    0
    1
         Lack of efficacy
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 1 patient discontinued during the placebo sequence of treatment due to lack of efficacy

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment Period 1
    Reporting group description
    		 -

    Reporting group values
    		 Treatment Period 1 Total
    Number of subjects
    		 14 14
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 11 11
        From 65-84 years
    		 3 3
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 49 ± 14 -
    Gender categorical
    Units: Subjects
        Female
    		 8 8
        Male
    		 6 6
    Race
    Units: Subjects
        Caucasian
    		 11 11
        Hispanic
    		 2 2
        Black
    		 1 1
    Myasthenia Gravis Fondation of America (MGFA) classification at screening
    Units: Subjects
        IIa
    		 2 2
        IIb
    		 2 2
        IIIa
    		 8 8
        IVa
    		 2 2

    End points

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    End points reporting groups
    Reporting group title
    Eculizumab period 1
    Reporting group description
    		 Patients received eculizumab 600 mg via IVinfusion over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by 900 mg eculizumab via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.

    Reporting group title
    Placebo period 1
    Reporting group description
    		 Patients received placebo via IV infusion... more over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by matching placebo via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.
    Reporting group title
    Eculizumab period 2
    Reporting group description
    		 All these patients received placebo during period 1 During Period 2: Patients received eculizumab 600 mg via IV infusion over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by 900 mg eculizumab via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.

    Reporting group title
    Placebo period 2
    Reporting group description
    		 All these patients received eculizumab during period 1 During period 2: Patients received placebo via IV infusion... more over approximately 35 minutes once a week (every 7 ± 2 days) for 4 weeks followed by matching placebo via IV infusion over approximately 35 minutes every two weeks (every 14 ± 2 days) for 7 doses.

    Subject analysis set title
    Eculizumab Both Period
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Eculizumab Eculizumab: eculizumab 600 mg IV weekly for 4 doses followed by eculizumab 900 mg IV every two weeks for 7 doses

    Subject analysis set title
    Placebo Both Period
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Placebo Placebo: Placebo IV weekly for 4 doses then every two weeks for 7 doses

    Primary: Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity.

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    End point title
    		 Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity. [1]
    End point description
    The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG.
    End point type
    Primary
    End point timeframe
    16 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analysis provided for Quantitative Myasthenia Gravis (QMG): The Primary Efficacy Endpoint in This Study Was the Percentage of Patients With a 3-point Reduction From Baseline in the QMG Total Score for Disease Severity.
    End point values
    		 Eculizumab period 1 Placebo period 1
    Number of subjects analysed
    7
    7
    Units: percentage of patients
        number (not applicable)
    86
    57
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in QMG Total Score

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    End point title
    		 Mean Change From Baseline in QMG Total Score
    End point description
    The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The Myasthenia Gravis Foundation of America task force has recommended that the QMG score be used in prospective studies of therapy for MG. The QMG scoring system consists of 13 items. Each item is graded 0 to 3, with 3 being the most severe. The range of total QMG score is 0-39.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1 Eculizumab Both Period Placebo Both Period
    Number of subjects analysed
    7
    7
    7 [2]
    7 [3]
    Units: unit on a scale
        arithmetic mean (standard deviation)
    -7.43 ± 5.563
    -2.71 ± 4.855
    -7.92 ± 5.054
    -3.67 ± 4.008
    Notes
    [2] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    [3] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0144 [4]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.45
         upper limit
    		 -1.05
    Notes
    [4] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.117 [5]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.8
         upper limit
    		 1.37
    Notes
    [5] - No multiple comparisons or multiplicity adjustments were conducted

    Secondary: Change From Baseline in the MGFA Post-Intervention Status (PIS)

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    End point title
    		 Change From Baseline in the MGFA Post-Intervention Status (PIS)
    End point description
    The MGFA PIS is designed to assess the clinical state of MG patients at any time after treatment of MG is initiated. Change in status categories of Improved, Unchanged, Worse, Exacerbation, and Died of MG was to be assessed and recorded at every visit from Visits 3 to 24 (Weeks 1 to 16). Minimal manifestations were to be assessed at these visits.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1 Eculizumab period 2 Placebo period 2
    Number of subjects analysed
    7
    7
    6
    6
    Units: subject
        Improved
    5
    6
    6
    2
        Unchanged
    2
    1
    0
    4
        Worse
    0
    0
    0
    0
        Exacerbation
    0
    0
    0
    0
        Died of MG
    0
    0
    0
    0
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 1 [6]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [6] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Eculizumab period 2 v Placebo period 2
    Number of subjects included in analysis
    12
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0606 [7]
    Method
    		 Chi-squared
    Confidence interval
    Notes
    [7] - No multiple comparisons or multiplicity adjustments were conducted.

    Secondary: Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL)

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    End point title
    		 Change From Baseline in the MG-Activity of Daily Living Profile (MG-ADL)
    End point description
    The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living (ADL) in MG patients. The 8 items of the MG-ADL were derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 – 24. MG-ADL was to be performed at every study visit. The recall period for MG-ADL was since the preceding study visit (1 or 2 weeks).
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1 Eculizumab Both Period Placebo Both Period
    Number of subjects analysed
    7
    7
    7 [8]
    7 [9]
    Units: unit on a scale
        arithmetic mean (standard deviation)
    4.29 ± 1.799
    7.86 ± 3.716
    5.42 ± 3.315
    7 ± 3.464
    Notes
    [8] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    [9] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo Both Period v Eculizumab Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.1873 [10]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.08
         upper limit
    		 0.91
    Notes
    [10] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Placebo period 1 v Eculizumab period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.041 [11]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.97
         upper limit
    		 -0.17
    Notes
    [11] - No multiple comparisons or multiplicity adjustments were conducted.

    Secondary: Change From Baseline in the QoL Instrument, SF-36.

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    End point title
    		 Change From Baseline in the QoL Instrument, SF-36.
    End point description
    The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (physical functioning, role-physical, bodily pain, general health, mental health, role-emotional, social functioning and vitality) as well as psychometrically-based physical and mental health summary measures. It is a generic measure, as opposed to one that targets a specific age, disease or treatment group. The lower the score the more disability; the higher the score the less disability. Norm-based scoring involving a linear T-score transformation method was used so that scores for each of the health domain scales and component summary measures have a mean of 50 and a standard deviation of 10 based on the 1998 US general population. Thus, scores above and below 50 are above and below the average, respectively, in the 1998 US general.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1 Eculizumab Both Period Placebo Both Period
    Number of subjects analysed
    7
    7
    7 [12]
    7 [13]
    Units: unit on a scale
    arithmetic mean (standard deviation)
        Physical Functioning (Last Visit)
    56.43 ± 29.255
    64.29 ± 24.054
    57.92 ± 26.921
    57.08 ± 27.507
        Role Physical (Last Visit)
    61.61 ± 38.6
    68.75 ± 25.769
    64.06 ± 31.771
    60.94 ± 27.324
        Bodily Pain (Last Visit)
    60 ± 24.235
    74.86 ± 20.651
    66.75 ± 22.511
    76.17 ± 15.689
        General Health (Last Visit)
    47.86 ± 16.994
    40.43 ± 23.201
    44.67 ± 16.267
    37.5 ± 19.365
        Vitality (Last Visit)
    50 ± 23.936
    52.68 ± 15.67
    53.13 ± 19.31
    48.96 ± 18.238
        Social Functioning (Last Visit)
    66.07 ± 25.733
    82.14 ± 17.466
    66.67 ± 24.034
    78.13 ± 17.778
        Role Emotional (Last Visit)
    77.38 ± 36.233
    71.43 ± 29.603
    70.83 ± 34.542
    82.64 ± 25.981
        Mental Health (Last Visit)
    76.43 ± 17.728
    58.57 ± 25.284
    69.17 ± 20.542
    68.75 ± 23.27
        Physical Component Score (Last Visit)
    38.73 ± 10.235
    44.97 ± 7.721
    41.4 ± 8.591
    40.32 ± 10.025
        Mental Component Score (Last Visit)
    49.5 ± 12.066
    43.95 ± 12.53
    46.11 ± 12.596
    49.03 ± 11.476
    Notes
    [12] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    [13] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    No multiple comparisons or multiplicity adjustments were conducted.
    Comparison groups
    Placebo Both Period v Eculizumab Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.919
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.94
         upper limit
    		 18.6
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo period 1 v Eculizumab period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority [14]
    P-value
    		 = 0.5931
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -7.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.05
         upper limit
    		 23.33
    Notes
    [14] - Physical Functioning
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Role Physical
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.7319 [15]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.64
         upper limit
    		 22.89
    Notes
    [15] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Role Physical
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.691 [16]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Median difference (net)
    Point estimate
    -7.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -45.36
         upper limit
    		 31.08
    Notes
    [16] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 5
    Statistical analysis description
    Bodily Pain
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.1311 [17]
    Method
    		 paired t-test
    Parameter type
    		 Median difference (net)
    Point estimate
    -9.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22.18
         upper limit
    		 3.34
    Notes
    [17] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 6
    Statistical analysis description
    Bodily Pain
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.2406 [18]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -14.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.08
         upper limit
    		 11.36
    Notes
    [18] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 7
    Statistical analysis description
    General Health
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0578 [19]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    7.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.29
         upper limit
    		 14.62
    Notes
    [19] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 8
    Statistical analysis description
    General Health
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.5073 [20]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    7.43
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.26
         upper limit
    		 31.11
    Notes
    [20] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 9
    Statistical analysis description
    Vitality
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.2474 [21]
    Method
    		 paired t-test
    Parameter type
    		 Median difference (net)
    Point estimate
    4.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.39
         upper limit
    		 11.72
    Notes
    [21] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 10
    Statistical analysis description
    Vitality
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.8085 [22]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.24
         upper limit
    		 20.88
    Notes
    [22] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 11
    Statistical analysis description
    Social Functioning
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0716 [23]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    -11.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.13
         upper limit
    		 1.21
    Notes
    [23] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 12
    Statistical analysis description
    Social Functioning
    Comparison groups
    Placebo period 1 v Eculizumab period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.1966 [24]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -16.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.86
         upper limit
    		 9.54
    Notes
    [24] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 13
    Statistical analysis description
    Role Emotional
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.1701 [25]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    -11.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.6
         upper limit
    		 5.99
    Notes
    [25] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 14
    Statistical analysis description
    Role emotional
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.7422 [26]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    5.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.58
         upper limit
    		 44.48
    Notes
    [26] - No multiple comparison or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 15
    Statistical analysis description
    Mental Health
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.9007 [27]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.42
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.83
         upper limit
    		 7.67
    Notes
    [27] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 16
    Statistical analysis description
    Mental Health
    Comparison groups
    Placebo period 1 v Eculizumab period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.1519 [28]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    17.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.57
         upper limit
    		 43.29
    Notes
    [28] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 17
    Statistical analysis description
    Physical Component Score
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.6807 [29]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.57
         upper limit
    		 6.72
    Notes
    [29] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 18
    Statistical analysis description
    Physical Component Score
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.2226 [30]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Median difference (net)
    Point estimate
    -6.23
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.79
         upper limit
    		 4.32
    Notes
    [30] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 19
    Statistical analysis description
    Mental Component Score
    Comparison groups
    Placebo Both Period v Eculizumab Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.1505 [31]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.1
         upper limit
    		 1.26
    Notes
    [31] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 20
    Statistical analysis description
    Mental Component Score
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.4151 [32]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    5.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.77
         upper limit
    		 19.87
    Notes
    [32] - No multiple comparisons or multiplicity adjustments were conducted.

    Secondary: Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles

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    End point title
    		 Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles
    End point description
    Change from Baseline in Forced Vital Capacity
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1 Eculizumab Both Period Placebo Both Period
    Number of subjects analysed
    7
    7
    7 [33]
    7 [34]
    Units: percentage of predicted
    arithmetic mean (standard deviation)
        Change From Baseline in Respiratory Function Tests
    76.43 ± 15.328
    87 ± 23.544
    80 ± 14.894
    76.75 ± 23.152
    Notes
    [33] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    [34] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Forced Vital Capacity
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.3377 [35]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.94
         upper limit
    		 10.44
    Notes
    [35] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    No multiple comparisons or multiplicity adjustments were conducted.
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.3391 [36]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Median difference (net)
    Point estimate
    -10.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.71
         upper limit
    		 12.56
    Notes
    [36] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Negative Inspiratory Force
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.35
         upper limit
    		 4.35
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Negative Inspiratory Force
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.2292 [37]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (net)
    Point estimate
    -6.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.87
         upper limit
    		 4.73
    Notes
    [37] - No multiple comparisons or multiplicity adjustments were conducted.

    Secondary: Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles

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    End point title
    		 Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles
    End point description
    Change from Baseline in Forced Vital Capacity
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1 Eculizumab Both Period Placebo Both Period
    Number of subjects analysed
    7
    7
    7 [38]
    7 [39]
    Units: Percentage of Predicted
    arithmetic mean (standard deviation)
        Change from Baseline in Respiratory Function Test
    76.43 ± 15.328
    87 ± 23.544
    80 ± 14.894
    76.75 ± 23.152
    Notes
    [38] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    [39] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Forced Vital Capacity
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.3377 [40]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.94
         upper limit
    		 10.44
    Notes
    [40] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    Forced Vital Capacity
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.3391 [41]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Median difference (net)
    Point estimate
    -10.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.71
         upper limit
    		 12.56
    Notes
    [41] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 3
    Statistical analysis description
    Negative Inspiratory Force
    Comparison groups
    Eculizumab Both Period v Placebo Both Period
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 1 [42]
    Method
    		 paired t-test
    Parameter type
    		 Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.35
         upper limit
    		 4.35
    Notes
    [42] - No multiple comparisons or multiplicity adjustments were conducted.
    Statistical analysis title
    		 Statistical Analysis 4
    Statistical analysis description
    Negative Inspiratory Force
    Comparison groups
    Eculizumab period 1 v Placebo period 1
    Number of subjects included in analysis
    14
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.2292 [43]
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -6.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.87
         upper limit
    		 4.73
    Notes
    [43] - No multiple comparisons or multiplicity adjustments were conducted.

    Secondary: Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles

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    End point title
    		 Change From Baseline in Respiratory Function Tests to Characterize the Degree of Involvement of Respiratory Muscles
    End point description
    Change from Baseline in Negative Inspiratory Force. NIF is a measurement of respiratory muscle strength and ventilator reserve. NIF is represented by centimeters of water pressure (cmH2O). A normal NIF measurement is negative 60 cmH2O, or as 100% predicted value.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1 Eculizumab Both Period Placebo Both Period
    Number of subjects analysed
    7
    7
    7 [44]
    7 [45]
    Units: Percentage of Predicted
    arithmetic mean (standard deviation)
        Change From Baseline in Respiratory Function Tests
    92.43 ± 13.464
    99 ± 2.646
    93.5 ± 12.087
    93.5 ± 12.042
    Notes
    [44] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    [45] - There are 12 subjects in this group (Eculizumab period 1+ Eculizumab period 2)
    No statistical analyses for this end point

    Secondary: Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision)

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    End point title
    		 Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Double Vision)
    End point description
    The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1
    Number of subjects analysed
    7 [46]
    7 [47]
    Units: Unit on a scale
    arithmetic mean (standard deviation)
        Change From Baseline to the End of Treatment
    -0.71 ± 1.113
    -0.29 ± 0.488
    Notes
    [46] - Eculizumab
    [47] - Placebo
    No statistical analyses for this end point

    Secondary: Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis)

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    End point title
    		 Change From Baseline to the End of Treatment (16 Weeks) in the Two Most Affected QMG Items for Disease Severity (Individual Test Item: Ptosis)
    End point description
    The QMG scoring system is considered to be an objective evaluation of muscle strength based on quantitative testing of sentinel muscle groups. The MGFA task force has recommended that the QMG score be used in prospective studies of therapy for MG.
    End point type
    Secondary
    End point timeframe
    16 weeks
    End point values
    		 Eculizumab period 1 Placebo period 1
    Number of subjects analysed
    4 [48]
    4 [49]
    Units: Unit on a scale
    arithmetic mean (standard deviation)
        Change From Baseline to the End of Treatment
    -1 ± 1.155
    -0.5 ± 1
    Notes
    [48] - Eculizumab
    [49] - Placebo
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    46 weeks (Screening Period [up to 4 weeks], Treatment Period 1 [16 weeks], Washout Period [5 weeks], Treatment Period 2 [16 weeks], Follow-up Period [5 weeks]) for adverse events (AEs); 42 weeks for treatment emergent AEs (TEAEs).
    Adverse event reporting additional description
    TEAEs were collected at every visit and follow-up
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    11.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Placebo Placebo: Placebo IV weekly for 4 doses then every two weeks for 7 doses Events that occurred during the Washout Period were attributed to treatment assignment during Treatment Period 1.

    Reporting group title
    Eculizumab
    Reporting group description
    		 Eculizumab Eculizumab: eculizumab 600 mg IV weekly for 4 doses followed by eculizumab 900 mg IV every two weeks for 7 doses Events that occurred during the Washout Period were attributed to treatment assignment during Treatment Period 1.

    Serious adverse events
    		 Placebo Eculizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 13 (7.69%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Nervous system disorders
    Myasthenia Gravis A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia Gravis Crisis A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (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
    		 Placebo Eculizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 13 (84.62%)
    13 / 13 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acrochordon A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Haematoma A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Application Site Pruritus A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Chest Discomfort A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Chest Pain A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Cyst A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Fatigue A †
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 13 (15.38%)
         occurrences all number
    1
    2
    Influenza Like Illness A †
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Pain A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Pyrexia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Vessel Puncture Site Haematoma A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Hepatic Steatosis A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Erectile Dysfunction A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Menstrual Disorder A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Polymenorrhoea A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough A †
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 13 (23.08%)
         occurrences all number
    0
    4
    Dysphonia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Dyspnoea A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Hyperventilation A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Pharyngolaryngeal Pain A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Respiratory Tract Congestion A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Insomnia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Investigations
    Heart Rate Increased A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Lymphocyte Count Decreased A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Weight Decreased A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Weight Increased A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    White Blood Cell Count Decreased A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Injury, poisoning and procedural complications
    Contusion A †
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 13 (15.38%)
         occurrences all number
    3
    2
    Limb Injury A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Muscle Strain A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Procedural Nausea A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Scratch A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Tendon Rupture A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Tooth Fracture A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Wound A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nervous system disorders
    Carpal Tunnel Syndrome A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Cholinergic Syndrome A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Dizziness A †
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Headache A †
         subjects affected / exposed
    4 / 13 (30.77%)
    3 / 13 (23.08%)
         occurrences all number
    9
    14
    Memory Impairment A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Presyncope A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Sensory Disturbance A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Sinus Headache A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Haematochezia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Leukopenia A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Lip Dry A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nausea A †
         subjects affected / exposed
    2 / 13 (15.38%)
    4 / 13 (30.77%)
         occurrences all number
    4
    9
    Eye disorders
    Diplopia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Eye Discharge A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Lacrimation Increased A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Ocular Hyperaemia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal Discomfort A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Abdominal Pain A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Abdominal Pain Upper A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Constipation A †
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Dental Caries A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Diarrhoea A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Oesophageal Food Impaction A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Salivary Gland Enlargement A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Vomiting A †
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Skin and subcutaneous tissue disorders
    Dermatitis Allergic A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Eczema A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Erythema A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Hyperhidrosis A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Pruritus Generalised A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Rash A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Skin Lesion A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Haematuria A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nephrolithiasis A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia A †
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Back Pain A †
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 13 (30.77%)
         occurrences all number
    3
    5
    Bone Pain A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Muscle Spasms A †
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    3
    Musculoskeletal Pain A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Musculoskeletal Stiffness A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Myalgia A †
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 13 (23.08%)
         occurrences all number
    5
    3
    Neck Pain A †
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 13 (23.08%)
         occurrences all number
    1
    3
    Pain In Extremity A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Bronchitis A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Cellulitis A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Fungal Infection A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Gastroenteritis Viral A †
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Influenza A †
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Nasopharyngitis A †
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 13 (23.08%)
         occurrences all number
    3
    3
    Onychomycosis A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Oral Infection A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Rhinitis A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Sinusitis A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Upper Respiratory Tract Infection A †
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Viral Infection A †
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 13 (15.38%)
         occurrences all number
    2
    2
    Viral Upper Respiratory Tract Infection A †
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Type 2 Diabetes Mellitus A †
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Mar 2009
    Amendment 2 (US only) To address the recruitment concerns, this amendment will remove the inclusion criterion #3 "Duration of MG symptoms less than or equal to 10 years" and modify exclusion criterion #3 to specify a patient with MG status that, in the opinion of the Investigator, has reached a "burned out" stage will be excluded. This change will allow the recruitment of patients who have a likelihood of response to therapy based on their disease severity and MG treatment history.
    07 May 2009
    Amendment 2 (Canada Only) To address the recruitment concerns, this amendment will remove the inclusion criterion #3 "Duration ofMG symptoms less than or equal to 10 years" and modify exclusion criterion #3 to specify a patient with MG status that, in the opinion of the Investigator, has reached a "burned out" stage will be excluded. This change will allow the recruitment of patients who have a likelihood of response to therapy based on their disease severity and MG treatment history.
    17 Nov 2009
    Amendment 4 (UK Only) The purpose of this Amendment is to specify that women of childbearing potential must use adequate contraception methods during the study and for 5 months after treatment.

    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.
    Small sample size limited ability to detect intercohort differences. Carryover effect from Treatment Period (TP) 1 warrants cautious interpretation of TP 2 data. Study terminated early; 13 patients received eculizumab or placebo in TP2.
    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.

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