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    Clinical Trial Results:
    A Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Belimumab in Subjects with Generalized Myasthenia Gravis (MG).

    Summary
    EudraCT number
    		 2011-002068-26
    Trial protocol
    		 DE   IT  
    Global end of trial date
    27 Oct 2015

    Results information
    Results version number
    		 v3(current)
    This version publication date
    01 Jan 2017
    First version publication date
    08 Apr 2016
    Other versions
    		 v1 , v2
    Version creation reason
    • Correction of full data set
    Corrections required per ctgov changes.

    Trial information

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    Trial identification
    Sponsor protocol code
    BEL115123
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    GSK Response Center, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343, GlaxoSmithKline, +44 (0)208990 4466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343, GlaxoSmithKline, +44 (0)208990 4466, GSKClinicalSupportHD@gsk.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
    03 Dec 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Aug 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Oct 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of belimumab in subjects with MG by testing the hypothesis that belimumab will be more effective than placebo in reducing signs of MG as measured by the Quantitative Myasthenia Gravis (QMG) score.
    Protection of trial subjects
    N/A
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Apr 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Italy: 11
    Country: Number of subjects enrolled
    Canada: 9
    Country: Number of subjects enrolled
    United States: 19
    Worldwide total number of subjects
    40
    EEA total number of subjects
    12
    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)
    26
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants (par.) with myasthenia gravis (MG) and who were acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) antibody positive, on current standard of care therapy and continued to exhibit signs of MG were eligible for participation in the study.

    Pre-assignment
    Screening details
    		 The study was conducted in 3 phases: a 4 week screening period, a 24 week Treatment (trt) Period, and a 12 week Follow-up period. A total of 40 par. were enrolled, however 1 par. withdrew due to MG exacerbation on Day 7 prior to the first efficacy assessment; therefore, 39 par. comprise the Intent-to-Treat (ITT) Population.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo IV
    Arm description
    		 Participants received 250 milliliter (ml) of a normal saline placebo administered as intravenous (IV) infusion on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.
    Arm type
    		 Placebo Comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo was given by using normal saline bags without belimumab administered as Intravenous infusion every 4 weeks for 20 weeks (with an additional dose at Week 2).

    Arm title
    		 Belimumab 10 mg/kg IV
    Arm description
    		 Participants received 10 milligrams per kilogram (mg/kg) of belimumab administered as IV infusion in 250 mL normal saline on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Belimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Belimumab (400 mg in a 20 mL vial) is supplied as a reconstituted solution with a unit dose strength of 10 mg/kg administered as Intravenous infusion every 4 weeks for 20 weeks (with an additional dose at Week 2).

    Number of subjects in period 1 [1]
    		Placebo IV Belimumab 10 mg/kg IV
    Started
    21
    18
    Completed
    17
    16
    Not completed
    4
    2
         Adverse event, serious fatal
    1
    -
         Adverse event, non-fatal
    2
    -
         MG exacerbation or change in medication
    1
    2
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 40 participants were enrolled, however 1 participant withdrew due to MG exacerbation on Day 7 prior to the first efficacy assessment; therefore, 39 participants comprise the ITT Population which is presented in the subject disposition.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo IV
    Reporting group description
    		 Participants received 250 milliliter (ml) of a normal saline placebo administered as intravenous (IV) infusion on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.

    Reporting group title
    Belimumab 10 mg/kg IV
    Reporting group description
    		 Participants received 10 milligrams per kilogram (mg/kg) of belimumab administered as IV infusion in 250 mL normal saline on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.

    Reporting group values
    		 Placebo IV Belimumab 10 mg/kg IV Total
    Number of subjects
    		 21 18 39
    Age categorical
    Units: Subjects
    Age continuous
    Data are presented for the ITT Population which includes participants in the Safety Population (defined as all participants with at least one infusion of study agent) who have provided any post treatment efficacy assessment.
    Units: years
        arithmetic mean (standard deviation)
    		 59 ( 13.88 ) 52.7 ( 17.32 ) -
    Gender categorical
    Data are presented for the ITT Population which includes participants in the Safety Population (defined as all participants with at least one infusion of study agent) who have provided any post treatment efficacy assessment.
    Units: Subjects
        Female
    		 14 10 24
        Male
    		 7 8 15
    Race
    Data are presented for the ITT Population which includes participants in the Safety Population (defined as all participants with at least one infusion of study agent) who have provided any post treatment efficacy assessment.
    Units: Subjects
        American Indian or Alaskan Native
    		 1 0 1
        Asian - East Asian Heritage
    		 1 1 2
        White - White/Caucasian/European Heritage
    		 19 17 36

    End points

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    End points reporting groups
    Reporting group title
    Placebo IV
    Reporting group description
    		 Participants received 250 milliliter (ml) of a normal saline placebo administered as intravenous (IV) infusion on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.

    Reporting group title
    Belimumab 10 mg/kg IV
    Reporting group description
    		 Participants received 10 milligrams per kilogram (mg/kg) of belimumab administered as IV infusion in 250 mL normal saline on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.

    Subject analysis set title
    Placebo IV
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants received 250 ml of a normal saline placebo administered as IV infusion on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period. Intent-to-Treat (ITT) Population includes participants in the Safety Population who has provided any post treatment efficacy assessment.

    Subject analysis set title
    Belimumab 10 mg/kg IV
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants received 10 mg/kg of belimumab administered as IV infusion in 250 mL normal saline on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period. Intent-to-Treat (ITT) Population includes participants in the Safety Population who has provided any post treatment efficacy assessment.

    Primary: Mean change from Baseline for quantitative myasthenia gravis (QMG) score at Week 24

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    End point title
    		 Mean change from Baseline for quantitative myasthenia gravis (QMG) score at Week 24
    End point description
    The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The total QMG score was calculated by adding the score of each of the 13 individual QMG questions. Possible scoring on the QMG range from 0 (normal) to 39 (severe). A lower score indicates a better clinical outcome. The QMG score at Baseline is the average of the screening and Week 0 Baseline scores. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. The differences in adjusted least square means were presented (Belimumab 10 mg/kg minus Placebo). A negative treatment difference indicates benefit relative to placebo. The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline QMG Score, Treatment by Visit, and Baseline QMG Score by Visit.
    End point type
    Primary
    End point timeframe
    Baseline and Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    17 [1]
    17 [2]
    Units: Units on a scale
        least squares mean (standard error)
    -2.37 ( 1.099 )
    -4.21 ( 1.143 )
    Notes
    [1] - ITT: includes participants in the Safety Population who has provided any post tx efficacy assessment
    [2] - ITT: includes participants in the Safety Population who has provided any post tx efficacy assessment
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Belimumab 10 mg/kg IV v Placebo IV
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.256
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.08
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.592

    Secondary: Number of participants with improvement by greater than or equal to (>=) 3 points from Baseline through to Week 24 in the QMG score

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    End point title
    		 Number of participants with improvement by greater than or equal to (>=) 3 points from Baseline through to Week 24 in the QMG score
    End point description
    The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The total QMG score was calculated by adding the score of each of the 13 individual QMG questions. Possible scoring on the QMG range from 0 (normal) to 39 (severe). A lower score indicates a better clinical outcome. The QMG score at Baseline is the average of the screening and Week 0 Baseline scores. Proportions compared using exact analyses stratified by the observed median Baseline score (less than or equal to [<=] median, greater than [ >] median). Exact odds ratio, double the exact one-sided p-value and exact confidence intervals were presented. Participants with missing data were assumed to have a negative response.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [3]
    18 [4]
    Units: Number of participants
        number (not applicable)
    6
    11
    Notes
    [3] - ITT Population
    [4] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.082
    Method
    		 exact methods
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 19.02

    Secondary: Number of participants worsening by >=3 points in QMG score from Baseline through to Week 24

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    End point title
    		 Number of participants worsening by >=3 points in QMG score from Baseline through to Week 24
    End point description
    The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The total QMG score was calculated by adding the score of each of the 13 individual QMG questions. Possible scoring on the QMG range from 0 (normal) to 39 (severe). A lower score indicates a better clinical outcome. The QMG score at Baseline is the average of the screening and Week 0 Baseline scores. Proportions compared using exact analyses stratified by the observed median Baseline score (<=median, > median). Exact odds ratio, double the exact one-sided p-value and exact confidence interval were presented. Participants with missing data were assumed to have a worsening response.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [5]
    18 [6]
    Units: Number of participants
        number (not applicable)
    4
    2
    Notes
    [5] - ITT Population
    [6] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.827
    Method
    		 exact methods
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.05
         upper limit
    		 4.35

    Secondary: Number of participants with a sustained response in the QMG score

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    End point title
    		 Number of participants with a sustained response in the QMG score
    End point description
    A sustained response during the treatment phase is when a participant improves by >=3 points from Baseline at Week 12, and the participant maintains at least a 3 point improvement from Baseline through Week 24. The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The total QMG score was calculated by adding the score of each of the 13 individual QMG questions. Possible scoring on the QMG range from 0 (normal) to 39 (severe). A lower score indicates a better clinical outcome. The QMG score at Baseline is the average of the screening and Week 0 Baseline scores. Odds ratios are calculated by Cochran-Mantel-Haenszel method stratified by the observed median baseline score (<= median, > median). Wald confidence intervals and p-values were presented.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [7]
    18 [8]
    Units: Number of participants
        number (not applicable)
    5
    8
    Notes
    [7] - ITT Population
    [8] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.184
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 10.1

    Secondary: Mean change from Baseline for QMG score at Week 28, Week 32 and Week 36

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    End point title
    		 Mean change from Baseline for QMG score at Week 28, Week 32 and Week 36
    End point description
    The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. Total QMG score was calculated by adding the score of each of the 13 individual QMG questions. Possible scoring on the QMG range from 0 (mild) to 39 (severe). A lower score indicates a better clinical outcome. The QMG score at BL is the average of the screening and Week 0 BL scores. Change from BL was calculated by subtracting the BL value from the post-Baseline value. The differences in adjusted least square means are presented (Belimumab 10 mg/kg minus Placebo). A negative trt difference indicates benefit relative to placebo. Analysis method was Mixed-Model Repeated Measures adjusted for Trt, Visit, BL QMG Score, Trt by Visit and BL QMG Score by Visit. Only follow-up visits are presented but the analysis also includes all trt phase visits. Only those par. available at the indicated time points (represented by n=X, X in the category title) were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 28, Week 32 and Week 36
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [9]
    18 [10]
    Units: Units on a scale
    least squares mean (standard error)
        Week 28, n=16, 14
    -3.33 ( 0.839 )
    -5.03 ( 0.889 )
        Week 32, n=15, 16
    -2.82 ( 0.88 )
    -4.12 ( 0.904 )
        Week 36, n=17, 14
    -2.44 ( 0.872 )
    -4.73 ( 0.921 )
    Notes
    [9] - ITT Population
    [10] - ITT Population
    Statistical analysis title
    		 Statisitcal analysis 1
    Comparison groups
    Belimumab 10 mg/kg IV v Placebo IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [11]
    P-value
    		 = 0.175
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 0.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.228
    Notes
    [11] - Analysis for Week 28. Standard error of mean is for adjusted difference.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [12]
    P-value
    		 = 0.31
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.89
         upper limit
    		 1.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.267
    Notes
    [12] - Analysis for Week 32. Standard error of mean is for adjusted difference.
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [13]
    P-value
    		 = 0.081
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -2.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.88
         upper limit
    		 0.3
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.272
    Notes
    [13] - Analysis for Week 36. Standard error of mean is for adjusted difference.

    Secondary: Mean change from Baseline in Myasthenia Gravis Composite (MGC) scale through to Week 24

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    End point title
    		 Mean change from Baseline in Myasthenia Gravis Composite (MGC) scale through to Week 24
    End point description
    The total MGC score was calculated by adding the score of each of the 10 individual MGC questions. Possible total MGC scores range from 0 (normal) to 50 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participants last available assessment prior to initiation of study IV infusion. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. The differences in adjusted least square means are presented (Belimumab 10 mg/kg minus Placebo). A negative treatment difference indicates benefit relative to placebo. The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline MGC Score, Treatment by Visit, and Baseline MGC Score by Visit.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    17 [14]
    17 [15]
    Units: Units on a scale
        least squares mean (standard error)
    -3.86 ( 1.037 )
    -3.81 ( 1.064 )
    Notes
    [14] - ITT Population
    [15] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Standard error of mean is for adjusted difference.
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.972
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.97
         upper limit
    		 3.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.486

    Secondary: Number of participants with improvement by >=3 points from Baseline through to Week 24 in the MGC score

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    End point title
    		 Number of participants with improvement by >=3 points from Baseline through to Week 24 in the MGC score
    End point description
    The total MGC score was calculated by adding the score of each of the 10 individual MGC questions. Possible total MGC scores range from 0 (normal) to 50 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participants last available assessment prior to initiation of study IV infusion. Proportions compared using exact analyses stratified by the observed median baseline score (<= median, > median). Exact odds ratios, double the exact one-sided p-values and exact confidence intervals were presented. Participants with missing data were assumed to have a negative response.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [16]
    18 [17]
    Units: Number of participants
        number (not applicable)
    10
    9
    Notes
    [16] - ITT Population
    [17] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 1
    Method
    		 exact methods
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 5.48

    Secondary: Number of participants worsening by >=3 points from Baseline through to Week 24 in the MGC score

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    End point title
    		 Number of participants worsening by >=3 points from Baseline through to Week 24 in the MGC score
    End point description
    The total MGC score was calculated by adding the score of each of the 10 individual MGC questions. Possible total MGC scores range from 0 (normal) to 50 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participants last available assessment prior to initiation of study IV infusion. Proportions compared using exact analyses stratified by the observed median baseline score (<= median, > median). Exact odds ratios, double the exact one-sided p-values and exact confidence intervals were presented. Participants with missing data were assumed to have a worsening response.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [18]
    18 [19]
    Units: Number of participants
        number (not applicable)
    5
    2
    Notes
    [18] - ITT Population.
    [19] - ITT Population.
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.53
    Method
    		 exact methods
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.03
         upper limit
    		 2.89

    Secondary: Number of participants with a sustained response in the MGC score

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    End point title
    		 Number of participants with a sustained response in the MGC score
    End point description
    A sustained response during the treatment phase is when a participant improves by >=3 points from Baseline at Week 12, and the participant maintains at least a 3 point improvement from Baseline through Week 24. The total MGC score was calculated by adding the score of each of the 10 individual MGC questions. Possible total MGC scores range from 0 (normal) to 50 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participants last available assessment prior to initiation of study IV infusion. Odds ratios are calculated by Cochran-Mantel-Haenszel method without adjusting for any strata. Wald confidence intervals and p-values were presented.
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [20]
    18 [21]
    Units: Number of participants
        number (not applicable)
    4
    7
    Notes
    [20] - ITT Population
    [21] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.175
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 11.46

    Secondary: Mean change from Baseline in the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) at Week 12 and Week 24

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    End point title
    		 Mean change from Baseline in the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) at Week 12 and Week 24
    End point description
    The total MG-ADL score was calculated by adding the score of each of the 8 individual MG-ADL questions. Possible total MG-ADL scores ranges from 0 (normal) to 24 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participants last available assessment prior to initiation of study IV infusion. Change from Baseline was calculated by subtracting the Baseline value from the post-baseline value. The differences in adjusted least square means are presented (Belimumab 10 mg/kg minus Placebo). A negative treatment difference indicates benefit relative to placebo. The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline MG-ADL Score, Treatment by Visit, and Baseline MG-ADL Score by Visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 12 and Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [22]
    18 [23]
    Units: Units on a scale
    least squares mean (standard error)
        Week 12, n=19, 18
    -1.33 ( 0.489 )
    -1.83 ( 0.511 )
        Week 24, n=17, 17
    -2.01 ( 0.589 )
    -2.32 ( 0.603 )
    Notes
    [22] - ITT Population
    [23] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Statistical analysis is presented for Week 12. Standard error of mean is for adjusted mean difference.
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.483
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.94
         upper limit
    		 0.93
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.707
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Statistical analysis is presented for Week 24. Standard error of mean is for adjusted mean difference.
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.711
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.31
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.03
         upper limit
    		 1.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.844

    Secondary: Median time to QMG response which is sustained from earliest time point at which improvement by >=3 points from Baseline is observed and maintained through Week 24

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    End point title
    		 Median time to QMG response which is sustained from earliest time point at which improvement by >=3 points from Baseline is observed and maintained through Week 24
    End point description
    A sustained response during the treatment phase is when a participant improves by >=3 points from Baseline at Week 12, and the participant maintains at least a 3 point improvement from Baseline through Week 24. The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The total QMG score was calculated by adding the score of each of the 13 individual QMG questions. Possible scoring on the QMG range from 0 (normal) to 39 (severe). A lower score indicates a better clinical outcome. The QMG score at Baseline is the average of the screening and Week 0 Baseline scores. As per the criteria documented in the Reporting and Analysis Plan, these analyses were not conducted since <50% of subjects met the criteria (i.e. had the event in question).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    0 [24]
    0 [25]
    Units: weeks
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [24] - Greater than 50% of the participants did not had a response. Hence, the analysis was not performed.
    [25] - Greater than 50% of the participants did not had a response. Hence, the analysis was not performed.
    No statistical analyses for this end point

    Secondary: Median time to MGC response which is sustained from earliest time point at which improvement by >=3 points from Baseline is observed and maintained through Week 24

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    End point title
    		 Median time to MGC response which is sustained from earliest time point at which improvement by >=3 points from Baseline is observed and maintained through Week 24
    End point description
    A sustained response during the treatment phase is when a participant improves by >=3 points from Baseline at Week 12, and the participant maintains at least a 3 point improvement from Baseline through Week 24. The total MGC score was calculated by adding the score of each of the 10 individual MGC questions. Possible total MGC scores range from 0 (normal) to 50 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participants' last available assessment prior to initiation of study intravenous (IV) infusion. As per the criteria documented in the Reporting and Analysis Plan these analyses were not conducted since <50% of subjects met the criteria (i.e. had the event in question).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    0 [26]
    0 [27]
    Units: Weeks
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [26] - Greater than 50% of the participants did not had a response. Hence, the analysis was not performed.
    [27] - Greater than 50% of the participants did not had a response. Hence, the analysis was not performed.
    No statistical analyses for this end point

    Secondary: Mean change from Baseline for MGC score at Week 28, Week 32 and Week 36

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    End point title
    		 Mean change from Baseline for MGC score at Week 28, Week 32 and Week 36
    End point description
    The total MGC score was calculated by adding the score of each of the 10 individual MGC questions. Possible total MGC scores range from 0 (normal) to 50 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participant's last available assessment prior to initiation of study IV infusion. Change from Baseline was calculated by subtracting the Baseline value from the post-Baseline value. The differences in adjusted least square means are presented (Belimumab 10 mg/kg minus Placebo). A negative treatment difference indicates benefit relative to placebo. The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline MGC Score, Treatment by Visit, and Baseline MGC Score by Visit. Only follow-up visits are presented but the analysis also includes all treatment phase visits. Only those participants available at the indicated time points (represented by n=X, X in the category titles) were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 28, Week 32 and Week 36
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [28]
    18 [29]
    Units: Units on a scale
    least squares mean (standard error)
        Week 28, n=16, 14
    -4.63 ( 0.856 )
    -5.64 ( 0.905 )
        Week 32, n=15, 16
    -5.46 ( 0.975 )
    -5.44 ( 0.948 )
        Week 36, n=17, 14
    -4.77 ( 0.97 )
    -5.04 ( 1.052 )
    Notes
    [28] - ITT Population
    [29] - ITT Population
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Belimumab 10 mg/kg IV v Placebo IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    P-value
    		 = 0.423
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.56
         upper limit
    		 1.53
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.245
    Notes
    [30] - Analysis for Week 28. Standard error of mean is for adjusted difference.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Belimumab 10 mg/kg IV v Placebo IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    P-value
    		 = 0.986
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.76
         upper limit
    		 2.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.361
    Notes
    [31] - Analysis for Week 32. Standard error of mean is for adjusted difference.
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    Placebo IV v Belimumab 10 mg/kg IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    P-value
    		 = 0.848
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.21
         upper limit
    		 2.65
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.43
    Notes
    [32] - Analysis for Week 36. Standard error of mean is for adjusted difference.

    Secondary: Number of participants with a MGFA-PIS of minimal manifestation or better at Week 24 and Week 36

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    End point title
    		 Number of participants with a MGFA-PIS of minimal manifestation or better at Week 24 and Week 36
    End point description
    Myasthenia Foundation of America (MGFA) post intervention status (PIS) assesses whether subjects can be categorized as being in a status of Minimal Manifestation (MM), Pharmacologic Remission (PR) or Complete Remission (CR). Only MM and PR were assessed in this study as CR is not achievable based on the definition. The Reporting and Analysis Plan pre-specified that these analyses would not be conducted since during a review of blinded data it was identified that the MGFA scale had been inconsistently performed across sites and any statistical analyses would not be interpretable.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 36
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    0 [33]
    0 [34]
    Units: Number of participants
        number (not applicable)
    Notes
    [33] - ITT Population. Analysis would not be conducted.
    [34] - ITT Population. Analysis would not be conducted.
    No statistical analyses for this end point

    Secondary: Number of participants with MGFA-PIS of minimal manifestation sustained response (MM at Week 12 and maintained the response through Week 24)

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    End point title
    		 Number of participants with MGFA-PIS of minimal manifestation sustained response (MM at Week 12 and maintained the response through Week 24)
    End point description
    Myasthenia Foundation of America (MGFA) post intervention status (PIS) assesses whether subjects can be categorized as being in a status of Minimal Manifestation (MM), Pharmacologic Remission (PR) or Complete Remission (CR). Only MM and PR were assessed in this study as CR is not achievable based on the definition. The Reporting and Analysis Plan pre-specified that these analyses would not be conducted since during a review of blinded data it was identified that the MGFA scale had been inconsistently performed across sites and any statistical analyses would not be interpretable.
    End point type
    Secondary
    End point timeframe
    Week 12 through Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    0 [35]
    0 [36]
    Units: Number of participants
        number (not applicable)
    Notes
    [35] - ITT Population. Analysis would not be conducted.
    [36] - ITT Population. Analysis would not be conducted.
    No statistical analyses for this end point

    Secondary: Number of participants with MGFA-PIS of pharmacologic remission or better at Week 24 and Week 36

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    End point title
    		 Number of participants with MGFA-PIS of pharmacologic remission or better at Week 24 and Week 36
    End point description
    Myasthenia Foundation of America (MGFA) post intervention status (PIS) assesses whether subjects can be categorized as being in a status of Minimal Manifestation (MM), Pharmacologic Remission (PR) or Complete Remission (CR). Only MM and PR were assessed in this study as CR is not achievable based on the definition. The Reporting and Analysis Plan pre-specified that these analyses would not be conducted since during a review of blinded data it was identified that the MGFA scale had been inconsistently performed across sites and any statistical analyses would not be interpretable.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 36
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    0 [37]
    0 [38]
    Units: Number of participants
        number (not applicable)
    Notes
    [37] - ITT Population. Analysis would not be conducted.
    [38] - ITT Population. Analysis would not be conducted.
    No statistical analyses for this end point

    Secondary: Number of participants with MGFA-PIS of pharmacologic response sustained response (PR at week 12 and maintained the response through Week 24)

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    End point title
    		 Number of participants with MGFA-PIS of pharmacologic response sustained response (PR at week 12 and maintained the response through Week 24)
    End point description
    Myasthenia Foundation of America (MGFA) post intervention status (PIS) assesses whether subjects can be categorized as being in a status of Minimal Manifestation (MM), Pharmacologic Remission (PR) or Complete Remission (CR). Only MM and PR were assessed in this study as CR is not achievable based on the definition. The Reporting and Analysis Plan pre-specified that these analyses would not be conducted since during a review of blinded data it was identified that the MGFA scale had been inconsistently performed across sites and any statistical analyses would not be interpretable.
    End point type
    Secondary
    End point timeframe
    Week 12 through Week 24
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    0 [39]
    0 [40]
    Units: Number of participants
        number (not applicable)
    Notes
    [39] - ITT Population. Analysis would not be conducted.
    [40] - ITT Population. Analysis would not be conducted.
    No statistical analyses for this end point

    Secondary: Number of participants with MGFA-PIS (Unchanged, Improved, Worsened) at Week 24 and Week 36

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    End point title
    		 Number of participants with MGFA-PIS (Unchanged, Improved, Worsened) at Week 24 and Week 36
    End point description
    Myasthenia Foundation of America (MGFA) post intervention status (PIS) assesses whether subjects can be categorized as being unchanged, improved or worsened. The Reporting and Analysis Plan pre-specified that these analyses would not be conducted since during a review of blinded data it was identified that the MGFA scale had been inconsistently performed across sites and any statistical analyses would not be interpretable.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 36
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    0 [41]
    0 [42]
    Units: Number of participants
        number (not applicable)
    Notes
    [41] - ITT Population. Analysis would not be conducted.
    [42] - ITT Population. Analysis would not be conducted.
    No statistical analyses for this end point

    Secondary: Mean change from Baseline in the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) at Week 28, Week 32 and Week 36

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    End point title
    		 Mean change from Baseline in the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) at Week 28, Week 32 and Week 36
    End point description
    The total MG-ADL score was calculated by adding the score of each of the 8 individual MG-ADL questions. Possible total MG-ADL scores range from 0 (normal) to 24 (severe). A lower score indicates a better clinical outcome. Baseline is defined as the participant's last available assessment prior to initiation of study IV infusion. Change from Baseline was calculated by subtracting the Baseline value from the post-Baseline value. The differences in adjusted least square means are presented (Belimumab 10 mg/kg minus Placebo). A negative treatment difference indicates benefit relative to placebo. The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline MG-ADL Score, Treatment by Visit, and Baseline MG-ADL Score by Visit. Only follow-up visits are presented but the analysis also includes all treatment phase visits. Only those participants available at the indicated time points (represented by n=X, X in the category titles) were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 28, Week 32 and Week 36
    End point values
    		 Placebo IV Belimumab 10 mg/kg IV
    Number of subjects analysed
    21 [43]
    18 [44]
    Units: Units on a scale
    least squares mean (standard error)
        Week 28, n=16, 14
    -1.21 ( 0.522 )
    -2.96 ( 0.546 )
        Week 32, n=15, 16
    -1.52 ( 0.632 )
    -1.8 ( 0.619 )
        Week 36, n=17, 14
    -1.51 ( 0.621 )
    -1.78 ( 0.663 )
    Notes
    [43] - ITT Population
    [44] - ITT Population
    Statistical analysis title
    		 Statisitcal analysis 1
    Comparison groups
    Belimumab 10 mg/kg IV v Placebo IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [45]
    P-value
    		 = 0.028
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 -0.2
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.757
    Notes
    [45] - Analysis for Week 28. Standard error of mean is for adjusted difference.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Belimumab 10 mg/kg IV v Placebo IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [46]
    P-value
    		 = 0.756
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.1
         upper limit
    		 1.55
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.887
    Notes
    [46] - Analysis for Week 32. Standard error of mean is for adjusted difference.
    Statistical analysis title
    		 Statistical analysis 3
    Comparison groups
    Belimumab 10 mg/kg IV v Placebo IV
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [47]
    P-value
    		 = 0.775
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.12
         upper limit
    		 1.59
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.909
    Notes
    [47] - Analysis for Week 36. Standard error of mean is for adjusted difference.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the date first infusion of investigational product up to the Week 24 visit.
    Adverse event reporting additional description
    AEs and SAEs are reported for the safety population which is comprised of participants who had at least one infusion of study agent.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18
    Reporting groups
    Reporting group title
    Placebo IV
    Reporting group description
    		 Participants received 250 ml of a normal saline placebo administered as IV infusion on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.

    Reporting group title
    Belimumab 10 mg/kg IV
    Reporting group description
    		 Participants received 10 mg/kg of belimumab administered as IV infusion in 250 mL normal saline on Days 0, 14, 28 and then every 28 days through Week 20 of the treatment period. Participants continued with the standard of care therapy throughout the treatment period.

    Serious adverse events
    		 Placebo IV Belimumab 10 mg/kg IV
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 22 (18.18%)
    0 / 18 (0.00%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    1
    0
    Vascular disorders
    Aortic dissection rupture
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Myasthenia gravis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 18 (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 / 22 (4.55%)
    0 / 18 (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
    Nephrolithiasis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 18 (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
    Sepsis
         subjects affected / exposed
    1 / 22 (4.55%)
    0 / 18 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo IV Belimumab 10 mg/kg IV
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 22 (72.73%)
    14 / 18 (77.78%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    3
    1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 18 (11.11%)
         occurrences all number
    1
    2
    Fatigue
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Feeling hot
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Productive cough
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    3
    1
    Dyspnoea
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    Epistaxis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Throat tightness
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Wheezing
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    2
    0
    Depression
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Investigations
    Neutrophil count increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    White blood cell count increased
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Wound
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    1
    1
    Tooth fracture
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 22 (13.64%)
    1 / 18 (5.56%)
         occurrences all number
    6
    1
    Dizziness
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    1
    1
    Sciatica
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    1
    2
    Hypoaesthesia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Lethargy
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Somnolence
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    2
    2
    Eye pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Photopsia
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 22 (18.18%)
    1 / 18 (5.56%)
         occurrences all number
    5
    1
    Nausea
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 18 (16.67%)
         occurrences all number
    0
    6
    Abdominal pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Dental caries
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    3
    Photosensitivity reaction
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    2 / 22 (9.09%)
    2 / 18 (11.11%)
         occurrences all number
    2
    2
    Back pain
         subjects affected / exposed
    3 / 22 (13.64%)
    0 / 18 (0.00%)
         occurrences all number
    6
    0
    Muscle spasms
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    3
    1
    Groin pain
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    2
    Infections and infestations
    Influenza
         subjects affected / exposed
    0 / 22 (0.00%)
    3 / 18 (16.67%)
         occurrences all number
    0
    3
    Nasopharyngitis
         subjects affected / exposed
    2 / 22 (9.09%)
    1 / 18 (5.56%)
         occurrences all number
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 22 (4.55%)
    2 / 18 (11.11%)
         occurrences all number
    2
    2
    Cystitis
         subjects affected / exposed
    2 / 22 (9.09%)
    0 / 18 (0.00%)
         occurrences all number
    3
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 22 (4.55%)
    1 / 18 (5.56%)
         occurrences all number
    2
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Ear infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1
    Tooth infection
         subjects affected / exposed
    0 / 22 (0.00%)
    1 / 18 (5.56%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Aug 2011
    This amendment provides clarity for the conduct of the study and corrects typographical errors.
    11 Jun 2012
    Addition of a 3-hour clinical supervision period after subjects receive the first 2 infusions. Removal of the week 24 IP infusion (all efficacy and safety endpoints remain unchanged). Widen inclusion criteria to allow enrollment of MuSK antibody positive subjects. Enrollment to be stratified by MuSK antibody status. Revision to the timing of pharmacodynamic and pharmacokinetic endpoints.
    08 Aug 2013
    Safety sections updated to reflect new information on possible delayed hypersensitivity reactions. Amended timing such that analysis of data to be conducted twice – once when all subjects have reached week 24 (pre-specified primary endpoint) and again at week 36 when all subjects have completed post-treatment follow up). Criteria updated to exclude subjects positive for Hepatitis B surface antigen (HBsAg) and/or Hepatitis B core antibody (HBcAb). Patients who are positive for hepatitis C antibody but negative for a confirmatory RNA assay will be eligible to participate. Criteria updated to specify that doses of cholinesterase inhibitor which exceed 300 mg/day may be allowed after discussion with the GSK Medical Monitor. Removal of MGFA Post-Intervention status at Week 4, 8, 16, 20, 28 and 32. MG Composite Score (MGC) updated to include Mean change from baseline in MGC at Week 24. Mean change from baseline in MGC at Week 24 added as secondary endpoint under Multiple Comparisons Adjustments. Removed secondary endpoints from the Multiple Comparisons Adjustments section for Minimal Manifestation (MM) and Pharmacologic Response (PR). Footnotes in the Time and Events Table corrected.
    05 Mar 2014
    Progressive multifocal leukoencephalopathy (PML) has been reported in SLE patients receiving immunosuppressant pharmacotherapy, including belimumab. Section 6.3.8 updated to include this information.
    15 Apr 2014
    Allow enrollment of subjects taking methotrexate; reduce the time prior to screening for use of IVIg and/or plasmapheresis; and allow prior treatment with rituximab provided treatment was more than 12 months prior to screening.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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