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    Clinical Trial Results:
    A Double-masked, Placebo-controlled Study with Open-label Period to Evaluate the Efficacy and Safety of MEDI-551 in Adult Subjects with Neuromyelitis Optica and Neuromyelitis Optica Spectrum Disorders

    Summary
    EudraCT number
    		 2014-000253-36
    Trial protocol
    		 CZ   DE   EE   BG   PL   ES   HU   GR   NL  
    Global end of trial date
    06 Nov 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Nov 2021
    First version publication date
    19 Nov 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CD-IA-MEDI-551-1155
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02200770
    WHO universal trial number (UTN)
    		 U1111-1159-8686
    Sponsors
    Sponsor organisation name
    MedImmune LLC
    Sponsor organisation address
    OneMedImmune Way, Gaithersburg, United States, MD 20878
    Public contact
    MedImmune LLC, Global ClinicalLead, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    MedImmune LLC, Global ClinicalLead, +1 877-240-9479, information.center@astrazeneca.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
    09 Jun 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Nov 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to compare the efficacy of inebilizumab versus placebo in reducing the risk of an neuromyelitis optica spectrum disorders (NMOSD) attack in participants with NMOSD.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Jan 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Colombia: 15
    Country: Number of subjects enrolled
    Hong Kong: 4
    Country: Number of subjects enrolled
    Israel: 5
    Country: Number of subjects enrolled
    Japan: 8
    Country: Number of subjects enrolled
    Korea, Republic of: 19
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    Moldova, Republic of: 1
    Country: Number of subjects enrolled
    New Zealand: 1
    Country: Number of subjects enrolled
    Peru: 15
    Country: Number of subjects enrolled
    Russian Federation: 23
    Country: Number of subjects enrolled
    Serbia: 10
    Country: Number of subjects enrolled
    South Africa: 4
    Country: Number of subjects enrolled
    Taiwan: 3
    Country: Number of subjects enrolled
    Thailand: 11
    Country: Number of subjects enrolled
    Turkey: 4
    Country: Number of subjects enrolled
    United States: 41
    Country: Number of subjects enrolled
    Bulgaria: 9
    Country: Number of subjects enrolled
    Estonia: 3
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Hungary: 6
    Country: Number of subjects enrolled
    Poland: 21
    Country: Number of subjects enrolled
    Czechia: 8
    Worldwide total number of subjects
    231
    EEA total number of subjects
    56
    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)
    221
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 231 participants were randomised at 81 participating sites in 24 countries. Out of 231 participants, 1 participant was randomised but not treated due to an NMOSD attack on the day of randomisation prior to dosing.

    Period 1
    Period 1 title
    Randomized-controlled Period (RCP)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Inebilizumab
    Arm description
    		 Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received intravenous (IV) dose of placebo matched to inebilizumab on Day 1 and Day 15 of the randomized-controlled period (RCP). The participants who entered open-label period (OLP) received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the Safety Follow up Period (SFP) at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Intravenous dose of placebo matched to inebilizumab was administered on Day 1 and Day 15 of the RCP.

    Arm title
    		 Inebilizumab/Inebilizumab
    Arm description
    		 AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab (MEDI551) 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Inebilizumab
    Investigational medicinal product code
    MEDI-551
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of the RCP.

    Number of subjects in period 1 [1]
    		Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Started
    56
    174
    Completed
    54
    169
    Not completed
    2
    5
         Consent withdrawn by subject
    1
    1
         Adverse event, non-fatal
    -
    2
         Not specified
    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: Total 231 participants were randomized in the study, out of which one participant did not receive any treatment due to an NMOSD attack on the day of randomisation prior to dosing. Baseline characteristics are reported only for treated (230) participants.
    Period 2
    Period 2 title
    Open-label Period (OLP)
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Inebilizumab
    Arm description
    		 Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received intravenous (IV) dose of placebo matched to inebilizumab on Day 1 and Day 15 of the randomized-controlled period (RCP). The participants who entered open-label period (OLP) received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Inebilizumab
    Investigational medicinal product code
    Other name
    MEDI-551
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants who received placebo in RCP and entered in OLP received IV inebilizumab 300 mg on both Day 1 and Day 15 followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP.

    Arm title
    		 Inebilizumab/Inebilizumab
    Arm description
    		 AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab (MEDI551) 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants who received inebilizumab in RCP and entered in OLP received IV placebo matched to inebilizumab on Day 15.

    Investigational medicinal product name
    Inebilizumab
    Investigational medicinal product code
    Other name
    MEDI-551
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants who received inebilizumab in RCP and entered in OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP.

    Number of subjects in period 2 [2]
    		Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Started
    51
    165
    Completed
    43
    131
    Not completed
    8
    34
         Adverse event, serious fatal
    1
    2
         Consent withdrawn by subject
    -
    14
         Adverse event, non-fatal
    1
    2
         Not specified
    6
    15
         Lost to follow-up
    -
    1
    Notes
    [2] - 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: Three participants in Placebo/Inebilizumab arm and 4 participants in Inebilizumab/Inebilizumab arm, did not roll over to open-label period.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo/Inebilizumab
    Reporting group description
    		 Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received intravenous (IV) dose of placebo matched to inebilizumab on Day 1 and Day 15 of the randomized-controlled period (RCP). The participants who entered open-label period (OLP) received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the Safety Follow up Period (SFP) at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.

    Reporting group title
    Inebilizumab/Inebilizumab
    Reporting group description
    		 AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab (MEDI551) 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.

    Reporting group values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab Total
    Number of subjects
    		 56 174 230
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 52 168 220
        From 65-84 years
    		 4 6 10
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 42.6 ( 13.9 ) 43.0 ( 11.6 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 50 159 209
        Male
    		 6 15 21
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 5 14 19
        Asian
    		 8 39 47
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 5 15 20
        White
    		 28 92 120
        More than one race
    		 0 1 1
        Unknown or Not Reported
    		 10 13 23
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 15 28 43
        Not Hispanic or Latino
    		 41 146 187
        Unknown or Not Reported
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Placebo/Inebilizumab
    Reporting group description
    		 Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received intravenous (IV) dose of placebo matched to inebilizumab on Day 1 and Day 15 of the randomized-controlled period (RCP). The participants who entered open-label period (OLP) received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the Safety Follow up Period (SFP) at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.

    Reporting group title
    Inebilizumab/Inebilizumab
    Reporting group description
    		 AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab (MEDI551) 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.
    Reporting group title
    Placebo/Inebilizumab
    Reporting group description
    		 Aquaporin-4-antibody (AQP4-IgG) sero positive and sero negative participants received intravenous (IV) dose of placebo matched to inebilizumab on Day 1 and Day 15 of the randomized-controlled period (RCP). The participants who entered open-label period (OLP) received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.

    Reporting group title
    Inebilizumab/Inebilizumab
    Reporting group description
    		 AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab (MEDI551) 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.

    Subject analysis set title
    Any Inebilizumab
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 in RCP or IV inebilizumab 300 mg on both Day 1 and Day 15 in OLP; followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP.

    Primary: Time to Adjudication Committee (AC)-Determined NMOSD Attack During RCP

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    End point title
    		 Time to Adjudication Committee (AC)-Determined NMOSD Attack During RCP
    End point description
    The NMOSD attack is defined as the presence of new or worsening symptom(s) related to NMOSD that meet at least one of the 18 protocol-defined attack criteria. These criteria were developed in conjunction with a panel of disease experts and with Food and Drug Administration input, and were intended to be clinically meaningful, objective, quantifiable, and able to be used worldwide. Only attacks positively adjudicated by the AC were used for the primary analysis. The arbitrary numbers 0.99999, 99999.0, and 9999.9 signified the data for lower limit of Confidence Interval (CI), upper limit of CI, and median, respectively, were not calculated because there were insufficient NMOSD attacks to determine the data for the specified arm. The Intent-to-treat (ITT) population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment.
    End point type
    Primary
    End point timeframe
    Day 1 (Baseline) through Day 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    56
    174
    Units: Days
        median (confidence interval 95%)
    9999.9 (142.0 to 99999.0)
    9999.9 (0.99999 to 99999.0)
    Statistical analysis title
    		 Total Placebo Vs Total Inebilizumab
    Comparison groups
    Inebilizumab/Inebilizumab v Placebo/Inebilizumab
    Number of subjects included in analysis
    230
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.272
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1496
         upper limit
    		 0.4961

    Secondary: Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP

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    End point title
    		 Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the Last Visit of RCP
    End point description
    EDSS and its associated functional system (FS) score provide a system for quantifying disability and monitoring changes in the level of disability over time. EDSS is a scale for assessing neurologic impairment in multiple sclerosis (MS). It consists of 7 FS (visual FS, brainstem FS, pyramidal FS, cerebellar FS, sensory FS, bowel and bladder FS, and cerebral FS) which are used to derive EDSS score ranging from 0 (normal neurological exam) to 10 (death from MS). A negative change from baseline indicates improvement. A participant was considered to have a worsening in overall EDSS score of at least 2 if baseline EDSS score was 0, or at least 1 point if baseline EDSS score is 1 to 5, or at least 0.5 point if baseline EDSS score is 5.5 or more. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) through Day 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    56
    174
    Units: Percentage of Participants
        number (not applicable)
    33.9
    14.9
    Statistical analysis title
    		 Total Placebo Vs Total Inebilizumab
    Comparison groups
    Placebo/Inebilizumab v Inebilizumab/Inebilizumab
    Number of subjects included in analysis
    230
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0033
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.352
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1755
         upper limit
    		 0.7059

    Secondary: Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP

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    End point title
    		 Change From Baseline in Low-Contrast Visual Acuity Binocular Score to the Last Visit of RCP
    End point description
    Low-contrast visual acuity test is used to determine the number of letters that can be read on a standardized low-contrast Landolt C Broken Rings Chart held at a distance of 3 meters. Binocular score is the number of letters read correctly on an eye chart using both eyes simultaneously. The total score ranges from 0-70. Higher score indicates better vision. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment. Participants with low contrast visual acuity binocular score were analysed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) through Day 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    56
    171
    Units: Score on scale
        least squares mean (standard error)
    1.442 ( 1.217 )
    1.576 ( 0.935 )
    Statistical analysis title
    		 Total Placebo Vs Total Inebilizumab
    Comparison groups
    Placebo/Inebilizumab v Inebilizumab/Inebilizumab
    Number of subjects included in analysis
    227
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.9026
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.134
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.0254
         upper limit
    		 2.2941
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.096

    Secondary: Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP

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    End point title
    		 Cumulative Number of Active Magnetic Resonance Imaging (MRI) Lesions During RCP
    End point description
    The number of new gadolinium-enhancing lesions and new or enlarging T2 lesions were measured by MRI of the brain, optic nerve, and spinal cord. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment. Participants with observed MRI lesions were analysed for this endpoint.
    End point type
    Secondary
    End point timeframe
    From Screening (Day -28) to Day 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    32
    79
    Units: Number of lesions
        arithmetic mean (standard deviation)
    2.3 ( 1.3 )
    1.6 ( 1.0 )
    Statistical analysis title
    		 Total Placebo Vs Total Inebilizumab
    Comparison groups
    Placebo/Inebilizumab v Inebilizumab/Inebilizumab
    Number of subjects included in analysis
    111
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0034
    Method
    		 Negative Binomial Regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.566
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.3866
         upper limit
    		 0.8279

    Secondary: Number of NMOSD-related in-patient Hospitalizations During RCP

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    End point title
    		 Number of NMOSD-related in-patient Hospitalizations During RCP
    End point description
    Participants with relapsing NMOSD have recurrent attacks that can be severe and result in blindness, paralysis, and even death and consequently, such attacks frequently result in in-patient hospitalizations. In-patient hospitalization is defined as a stay in hospital that goes beyond midnight of the first day of admission. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment. Participants with in-patient hospitalisation were analysed for this endpoint.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) through Day 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    8
    11
    Units: Number of In-patient Hospitalizations
        arithmetic mean (standard deviation)
    1.4 ( 0.7 )
    1.0 ( 0 )
    Statistical analysis title
    		 Total Placebo Vs Total Inebilizumab
    Comparison groups
    Placebo/Inebilizumab v Inebilizumab/Inebilizumab
    Number of subjects included in analysis
    19
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0146
    Method
    		 Negative Binomial Regression
    Parameter type
    		 Rate Ratio
    Point estimate
    0.317
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.1257
         upper limit
    		 0.7972

    Secondary: Annualized AC-determined NMOSD Attack Rate During any Exposure to Inebilizumab

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    End point title
    		 Annualized AC-determined NMOSD Attack Rate During any Exposure to Inebilizumab
    End point description
    Annualized attack rate is defined as total number of AC-determined attacks divided by total person years. Total person-years is calculated as the sum of the person-years for individual participant. Person-year for individual participant = (Date of last day before safety follow-up period - first inebilizumab dose date +1)/365.25. Annualized AC-determined NMOSD attack rate during any exposure to inebilizumab (in RCP and OLP) is reported. Any inebilizumab population was analysed which included all participants who received at least one dose of inebilizumab either in the RCP or OLP.
    End point type
    Secondary
    End point timeframe
    For participants randomised to inebilizumab: Day 1 of RCP through end of OLP (approximately 3.5 years); and for participants randomised to placebo: Day 1 of OLP through the end of OLP (approximately 3 years)
    End point values
    		 Any Inebilizumab
    Number of subjects analysed
    225
    Units: Annualized attack rate
        number (not applicable)
    0.086
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP

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    End point title
    		 Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) During RCP
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the RCP. As-treated population was analysed which included all participants who received any dose of study drug and analysed according to the treatment received.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) through Day 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    56
    174
    Units: Participants
        TEAEs
    41
    127
        TESAEs
    6
    9
    No statistical analyses for this end point

    Secondary: Number of Participants With TEAEs and TESAEs During OLP

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    End point title
    		 Number of Participants With TEAEs and TESAEs During OLP
    End point description
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. Open-label population was analysed which included all participants who received at least one dose of inebilizumab during OLP.
    End point type
    Secondary
    End point timeframe
    Day 198 through end of OLP period (maximum of 3 years after the last participant entered, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    51
    165
    Units: Participants
        TEAEs
    45
    144
        TESAEs
    19
    22
    No statistical analyses for this end point

    Secondary: Number of Participants With TEAEs and TESAEs During SFP (Open-label Population)

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    End point title
    		 Number of Participants With TEAEs and TESAEs During SFP (Open-label Population)
    End point description
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. Participant who prematurely discontinued from the RCP or OLP entered in the SFP. Open-label population was analysed which included all participants who received at least one dose of inebilizumab during OLP.
    End point type
    Secondary
    End point timeframe
    Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    51
    165
    Units: Participants
        TEAEs
    3
    5
        TESAEs
    2
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population)

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    End point title
    		 Number of Participants With TEAEs and TESAEs During SFP (Non-OLP Population)
    End point description
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug during the OLP. Participant who prematurely discontinued from the RCP or OLP entered in the SFP. Non-OLP population was analysed which included all participants who received any dose of study drug, analysed according to the treatment received in RCP, but did not roll over to OLP.
    End point type
    Secondary
    End point timeframe
    Every 3 months for a total of 1 year after the last dose of study drug (approximately 3 years)
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    5
    9
    Units: Participants
        TEAEs
    2
    3
        TESAEs
    1
    1
    No statistical analyses for this end point

    Secondary: Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP

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    End point title
    		 Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During RCP
    End point description
    Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during RCP is reported. As-treated population was analysed which included all participants who received any dose of study drug and analysed according to the treatment received.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) through Day 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    56
    173
    Units: Participants
        Hemoglobin (decreased)
    0
    2
        Leukocytes (decreased)
    1
    11
        Lymphocytes (decreased)
    5
    35
        Lymphocytes (increased)
    4
    1
        Neutrophils (decreased)
    0
    10
        Alanine Aminotransferase (increased)
    1
    4
        Aspartate Aminotransferase (increased)
    2
    1
        Bilirubin (increased)
    2
    1
        Cholesterol (increased)
    2
    5
        Creatinine (increased)
    1
    5
        Gamma glutamyl transferase (increased)
    1
    6
        Glucose (decreased)
    1
    1
        Glucose (increased)
    5
    1
        Potassium (decreased)
    0
    1
        Sodium (decreased)
    1
    2
        Triglycerides (increased)
    2
    7
    No statistical analyses for this end point

    Secondary: Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP

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    End point title
    		 Number of Participants With at Least a 2-Grade Shift From Baseline to Worst Toxicity Grade in Hematology and Chemistry During OLP
    End point description
    Number of participants with at least a 2-grade shift from baseline to worst toxicity grade in hematology and chemistry during OLP is reported. As-treated population was analysed which included all participants who received any dose of study drug and analysed according to the treatment received.
    End point type
    Secondary
    End point timeframe
    Day 198 through end of OLP (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    51
    165
    Units: Participants
        Hemoglobin (decreased)
    2
    6
        Leukocytes (decreased)
    1
    12
        Lymphocytes (decreased)
    9
    21
        Lymphocytes (increased)
    1
    4
        Neutrophils (decreased)
    1
    16
        Alanine aminotransferase (increased)
    45
    2
        Albumin (decreased)
    0
    3
        Alkaline phosphatase (increased)
    1
    1
        Aspartate aminotransferase (increased)
    2
    3
        Cholesterol (increased)
    1
    5
        Creatinine (increased)
    3
    7
        Gamma glutamyl transferase (increased)
    1
    10
        Glucose (decreased)
    0
    3
        Glucose (increased)
    5
    5
        Potassium (decreased)
    0
    1
        Potassium (increased)
    1
    2
        Sodium (decreased)
    2
    1
        Triglycerides (increased)
    4
    6
        Urate (increased)
    1
    1
        Hemoglobin (increased)
    0
    1
        Bilirubin
    2
    0
    No statistical analyses for this end point

    Secondary: Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP)

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    End point title
    		 Time to Maximum Serum Concentration (Tmax) of Inebilizumab (During RCP) [1]
    End point description
    Time to maximum serum concentration of inebilizumab during RCP is reported. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment. Here, ‘n' denotes the number of participants who had adequate pharmacokinetic sample of inebilizumab per the specified dose levels (Dose 1 and Dose 2).
    End point type
    Secondary
    End point timeframe
    Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetic analysis was not planned for Placebo/Inebilizumab arm but only for Inebilizumab/Inebilizumab arm.
    End point values
    		 Inebilizumab/Inebilizumab
    Number of subjects analysed
    173
    Units: Days
    median (full range (min-max))
        Dose 1 (n = 173)
    0.07 (0.07 to 7.00)
        Dose 2 (n = 168)
    0.07 (0.07 to 14.00)
    No statistical analyses for this end point

    Secondary: Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP)

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    End point title
    		 Maximum Observed Serum Concentration (Cmax) of Inebilizumab (During RCP) [2]
    End point description
    Maximum observed serum concentration of inebilizumab during RCP is reported. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment. Here, ‘n' denotes the number of participants who had adequate pharmacokinetic sample of inebilizumab per the specified dose levels (Dose 1 and Dose 2).
    End point type
    Secondary
    End point timeframe
    Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetic analysis was not planned for Placebo/Inebilizumab arm but only for Inebilizumab/Inebilizumab arm.
    End point values
    		 Inebilizumab/Inebilizumab
    Number of subjects analysed
    173
    Units: μg/mL
    geometric mean (geometric coefficient of variation)
        Dose 1 (n = 173)
    97.7 ( 37.4 )
        Dose 2 (n = 168)
    108 ( 45.4 )
    No statistical analyses for this end point

    Secondary: Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP)

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    End point title
    		 Area Under the Serum Concentration Time Curve of the Dosing Interval (AUC0-14d) of Inebilizumab (During RCP) [3]
    End point description
    Area under the serum concentration time curve of the dosing interval (AUC0-14d) of inebilizumab during RCP is reported. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment. Here, ‘n' denotes the number of participants who had adequate pharmacokinetic sample of inebilizumab per the specified dose levels (Dose 1 and Dose 2).
    End point type
    Secondary
    End point timeframe
    Dose 1 (Pre and post dose on Day 1 and Day 8); and Dose 2 (pre and post dose on Day 15; and Days 29, 57, 85, 113, 155, and 197)
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Pharmacokinetic analysis was not planned for Placebo/Inebilizumab arm but only for Inebilizumab/Inebilizumab arm.
    End point values
    		 Inebilizumab/Inebilizumab
    Number of subjects analysed
    167
    Units: μg*d/mL
    geometric mean (geometric coefficient of variation)
        Dose 1 (n = 167)
    667 ( 31.3 )
        Dose 2 (n = 164)
    967 ( 39.6 )
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP)

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    End point title
    		 Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During RCP)
    End point description
    Number of participants with positive ADA titer to inebilizumab during RCP is reported. The ITT population was analysed which included all participants who were randomised, received any study drug, and grouped according to their randomised treatment. Here, ‘n' denotes the number of participants who had adequate ADA samples. Baseline (BL) was predose on Day 1.
    End point type
    Secondary
    End point timeframe
    Pre and post dose on Day 1; and on Days 29, 85, and 197
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    56
    174
    Units: Participants
        ADA +ve anytime including BL (n = 56, 174)
    8
    17
        ADA +ve at BL; not detected post-BL (n = 56, 171)
    0
    5
        ADA +ve post-BL; positive at BL (n = 56, 171)
    4
    7
        ADA +ve post-BL; not detected at BL (n = 56, 171)
    4
    5
    No statistical analyses for this end point

    Secondary: Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP)

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    End point title
    		 Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Inebilizumab (During OLP)
    End point description
    Number of participants with positive ADA titer to inebilizumab in OLP is reported. Open-label population was analysed which included all participants who received at least one dose of inebilizumab during OLP. Here, ‘n' denotes the number of participants who had adequate ADA samples. The BL was predose on Day 1.
    End point type
    Secondary
    End point timeframe
    Pre and post dose on Day 1; and on Days 92, 183, 274, and then every 6 months (maximum of 3 years after the last participant enters, until regulatory approval or study discontinuation, whichever occurs first) (approximately 3 years)
    End point values
    		 Placebo/Inebilizumab Inebilizumab/Inebilizumab
    Number of subjects analysed
    51
    165
    Units: Participants
        ADA +ve anytime including BL (n = 51, 165)
    9
    22
        ADA +ve at BL; not detected post-BL (n = 51, 162)
    0
    5
        ADA +ve post-BL and positive at BL (n = 51, 162)
    4
    7
        ADA +ve post-BL; not detected at BL (n = 51, 162)
    5
    10
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until last study visit (approximately 5 years 10 months)
    Adverse event reporting additional description
    Adverse events are reported for all 3 study periods combined (RCP, OLP, and SFP).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    Total Inebilizumab
    Reporting group description
    		 AQP4-IgG sero positive and sero negative participants received IV dose of inebilizumab 300 mg on Day 1 and Day 15 of RCP. The participants who entered OLP received IV inebilizumab 300 mg on Day 1 and matching placebo on Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.

    Reporting group title
    Total Placebo
    Reporting group description
    		 AQP4-IgG sero positive and sero negative participants received IV dose of placebo matched to inebilizumab on Day 1 and Day 15 of the RCP. The participants who entered open-label period (OLP) received IV inebilizumab 300 mg on both Day 1 and Day 15, followed by a single IV dose of inebilizumab 300 mg every 6 months until maximum of 3 years after the last participant enters the OLP. Participants had choice to enter in the SFP at any point during RCP or OLP and were free to pursue other treatment options otherwise prohibited during the RCP and OLP. Participants continued in the SFP for 12 months from last dose of study drug.

    Serious adverse events
    		 Total Inebilizumab Total Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    28 / 174 (16.09%)
    24 / 56 (42.86%)
         number of deaths (all causes)
    2
    1
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer female
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Shock
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 174 (0.57%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pickwickian syndrome
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 174 (0.57%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    International normalised ratio increased
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Burns third degree
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (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
    Migraine
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelitis transverse
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuromyelitis optica spectrum disorder
         subjects affected / exposed
    3 / 174 (1.72%)
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Optic neuritis
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral nerve palsy
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbosacral radiculopathy
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post cardiac arrest syndrome
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Unresponsive to stimuli
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uraemic encephalopathy
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Visual acuity reduced
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blindness unilateral
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis acute
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    1 / 174 (0.57%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus bladder
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    0 / 174 (0.00%)
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Steroid withdrawal syndrome
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 174 (1.15%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 174 (0.57%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Connective tissue disorder
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 174 (0.00%)
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Atypical pneumonia
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 174 (1.72%)
    3 / 56 (5.36%)
         occurrences causally related to treatment / all
    1 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    3 / 174 (1.72%)
    7 / 56 (12.50%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal abscess
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchiolitis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system infection
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chorioretinitis
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral discitis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neuroborreliosis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis chronic
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatitis A
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Progressive multifocal leukoencephalopathy
         subjects affected / exposed
    1 / 174 (0.57%)
    0 / 56 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    0 / 174 (0.00%)
    1 / 56 (1.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 174 (0.00%)
    2 / 56 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Total Inebilizumab Total Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    164 / 174 (94.25%)
    50 / 56 (89.29%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 174 (1.72%)
    3 / 56 (5.36%)
         occurrences all number
    9
    4
    Hypotension
         subjects affected / exposed
    1 / 174 (0.57%)
    3 / 56 (5.36%)
         occurrences all number
    1
    3
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    12 / 174 (6.90%)
    3 / 56 (5.36%)
         occurrences all number
    16
    3
    Influenza like illness
         subjects affected / exposed
    3 / 174 (1.72%)
    4 / 56 (7.14%)
         occurrences all number
    6
    6
    Pyrexia
         subjects affected / exposed
    7 / 174 (4.02%)
    5 / 56 (8.93%)
         occurrences all number
    10
    12
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    15 / 174 (8.62%)
    6 / 56 (10.71%)
         occurrences all number
    18
    15
    Psychiatric disorders
    Depression
         subjects affected / exposed
    8 / 174 (4.60%)
    6 / 56 (10.71%)
         occurrences all number
    8
    6
    Insomnia
         subjects affected / exposed
    10 / 174 (5.75%)
    6 / 56 (10.71%)
         occurrences all number
    10
    6
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    11 / 174 (6.32%)
    3 / 56 (5.36%)
         occurrences all number
    18
    3
    Infusion related reaction
         subjects affected / exposed
    22 / 174 (12.64%)
    9 / 56 (16.07%)
         occurrences all number
    44
    16
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    6 / 174 (3.45%)
    3 / 56 (5.36%)
         occurrences all number
    6
    3
    Headache
         subjects affected / exposed
    27 / 174 (15.52%)
    11 / 56 (19.64%)
         occurrences all number
    76
    13
    Hypoaesthesia
         subjects affected / exposed
    12 / 174 (6.90%)
    2 / 56 (3.57%)
         occurrences all number
    24
    3
    Paraesthesia
         subjects affected / exposed
    12 / 174 (6.90%)
    2 / 56 (3.57%)
         occurrences all number
    15
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    11 / 174 (6.32%)
    4 / 56 (7.14%)
         occurrences all number
    12
    4
    Eye disorders
    Dry eye
         subjects affected / exposed
    4 / 174 (2.30%)
    6 / 56 (10.71%)
         occurrences all number
    4
    6
    Eye pain
         subjects affected / exposed
    8 / 174 (4.60%)
    5 / 56 (8.93%)
         occurrences all number
    27
    5
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 174 (1.72%)
    4 / 56 (7.14%)
         occurrences all number
    3
    4
    Constipation
         subjects affected / exposed
    9 / 174 (5.17%)
    7 / 56 (12.50%)
         occurrences all number
    13
    7
    Diarrhoea
         subjects affected / exposed
    15 / 174 (8.62%)
    8 / 56 (14.29%)
         occurrences all number
    19
    10
    Gastritis
         subjects affected / exposed
    3 / 174 (1.72%)
    3 / 56 (5.36%)
         occurrences all number
    3
    3
    Nausea
         subjects affected / exposed
    11 / 174 (6.32%)
    8 / 56 (14.29%)
         occurrences all number
    16
    8
    Vomiting
         subjects affected / exposed
    9 / 174 (5.17%)
    5 / 56 (8.93%)
         occurrences all number
    11
    7
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    5 / 174 (2.87%)
    3 / 56 (5.36%)
         occurrences all number
    5
    3
    Eczema
         subjects affected / exposed
    4 / 174 (2.30%)
    4 / 56 (7.14%)
         occurrences all number
    5
    4
    Pruritus
         subjects affected / exposed
    7 / 174 (4.02%)
    6 / 56 (10.71%)
         occurrences all number
    7
    6
    Rash
         subjects affected / exposed
    6 / 174 (3.45%)
    3 / 56 (5.36%)
         occurrences all number
    10
    3
    Renal and urinary disorders
    Micturition urgency
         subjects affected / exposed
    2 / 174 (1.15%)
    3 / 56 (5.36%)
         occurrences all number
    2
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    28 / 174 (16.09%)
    12 / 56 (21.43%)
         occurrences all number
    37
    14
    Back pain
         subjects affected / exposed
    24 / 174 (13.79%)
    8 / 56 (14.29%)
         occurrences all number
    38
    8
    Muscle spasms
         subjects affected / exposed
    5 / 174 (2.87%)
    4 / 56 (7.14%)
         occurrences all number
    8
    6
    Muscular weakness
         subjects affected / exposed
    4 / 174 (2.30%)
    4 / 56 (7.14%)
         occurrences all number
    9
    4
    Myalgia
         subjects affected / exposed
    4 / 174 (2.30%)
    3 / 56 (5.36%)
         occurrences all number
    4
    5
    Pain in extremity
         subjects affected / exposed
    11 / 174 (6.32%)
    8 / 56 (14.29%)
         occurrences all number
    20
    13
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    12 / 174 (6.90%)
    5 / 56 (8.93%)
         occurrences all number
    13
    6
    Conjunctivitis
         subjects affected / exposed
    5 / 174 (2.87%)
    3 / 56 (5.36%)
         occurrences all number
    6
    5
    Influenza
         subjects affected / exposed
    17 / 174 (9.77%)
    4 / 56 (7.14%)
         occurrences all number
    20
    10
    Nasopharyngitis
         subjects affected / exposed
    38 / 174 (21.84%)
    11 / 56 (19.64%)
         occurrences all number
    69
    17
    Oral herpes
         subjects affected / exposed
    5 / 174 (2.87%)
    4 / 56 (7.14%)
         occurrences all number
    6
    8
    Rhinitis
         subjects affected / exposed
    9 / 174 (5.17%)
    2 / 56 (3.57%)
         occurrences all number
    10
    3
    Upper respiratory tract infection
         subjects affected / exposed
    28 / 174 (16.09%)
    10 / 56 (17.86%)
         occurrences all number
    51
    15
    Urinary tract infection
         subjects affected / exposed
    40 / 174 (22.99%)
    20 / 56 (35.71%)
         occurrences all number
    77
    54
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 174 (0.57%)
    4 / 56 (7.14%)
         occurrences all number
    1
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Jul 2014
    Changes were made to update Section 2.1.1 (Primary Objective) and Section 1.6.1 (Primary Hypothesis) as: revised participant population for the primary analysis to include both AQP4-IgG seropositive and seronegative participants; Section 2.2.1 (Primary Endpoint) as: revised the timeframe of the primary endpoint definition from Days 183 to 197 to coincide with increased length of RCP, extended by 2 weeks to account for 2-week oral corticosteroid use between Days 1 and 14; removed restriction that primary analysis will be based on AQP4-IgG seropositive participants. The changes were also made to Section 3.1.1 (Overview), Section 3.2.4.1 (Primary Endpoint), Section 4.1.2 (Inclusion Criteria), Section 4.2.1 (Enrollment/Screening Period), Section 4.2.2.1 (Randomized-controlled Treatment Period), and Section 4.2.2.2 (OLP)
    10 Dec 2015
    The majority of changes were to clarify text and tables. Some updates were made in response to scientific advice from the European Medicines Agency and others in response to updates to the Investigator's Brochure. Text in multiple sections was amended to clarify: • The eligibility of AQP4- IgG seronegative participants will be determined by an independent Ethics Committee to reflect actual practice. • Participants may exit the OLP at any time for any reason, including seeking alternative treatment options. • The study is event driven and enrollment of participants will stop when a total of 67 AC determined NMOSD attacks occur. • The study population may be increased up to 252 participants if the ratio of the cumulative number of AC-determined NMOSD attacks to participant ratio is approximately 27% or less. Also, changes are made to Protocol Synopsis, Section 3.1.1.1 (RCP), Section 4.1.2 (Inclusion Criteria), Section 4.1.3 (Exclusion Criteria), Section 4.2.4. (Managing Subjects With Worsening Attacks), Section 4.2.5 (Study Procedures for Attack Follow-up Visit), Section 4.8.2 (Sample Size and Power Calculations), and Section 5.2 (Definition of SAEs).
    18 Oct 2016
    This protocol amendment included text revisions to provide additional clarification for the following sections of the Protocol: Section 4.8.3.1 (Primary Analyses) and Section 4.8.3.2 (Additional Analyses of the Primary Endpoint): Based on feedback from FDA to allow a wider window for the statistical analysis of the primary endpoint to prevent valid attacks from being excluded from analysis; Section 4.8.10.2 (Futility Assessment) and Appendix 10 (Details of Futility Analysis): Text was clarified to provide further information on how the futility assessment will be performed.
    08 Mar 2017
    The primary reasons for changes included removal of the sample size reassessment (as agreed with the FDA) and the inclusion of clear guidance that stopping enrollment is event driven and based on the occurrence of 67 AC-determined NMOSD attacks or when 252 participants have been enrolled, whichever occurs first. In addition, the updates were included in Section 1.4 (Summary of Clinical Experience), Section 5.3 (Definition of adverse event of special interest), and Section 5.6.3 (progressive multifocal leukoencephalopathy).
    16 Jul 2018
    This amendment incorporates updates in definitions, processes for safety reporting, numerous administrative and personnel changes, and corrects existing errors. Changes are made in Synopsis, Section 3.1.1 (Overview), Section 3.1.1.1 (Screening Period), Section 4.1.1 (Number of Subjects), Section 4.2.1 (Enrollment/Screening Period), Section 4.8.2 (Sample Size and Power Calculations), Section 4.1.3 (Exclusion Criteria), Section 4.2.2.1 (RCP), Table 6 (Schedule of RCP Study Procedures), Section 4.2.2.2 (OLP), Table 7 (Schedule of OLP Study Procedures), Section 4.5.1.2 (Treatment Administration), Section 4.3.1.2 (Neuroaxis MRI Scan), Section 4.7.2 (Prohibited Concomitant Medications), and Section 5.6.2 (Hepatic Function Abnormality).
    11 Oct 2018
    The primary purpose of this amendment was to make changes to the protocol based on the recommendations from the Independent Data Monitoring Committee, based on evidence of efficacy and safety, to stop study enrollment and allow participants in the RCP at that time the option to enter the OLP. In addition, minor copy-editing and formatting issues were corrected throughout the document. Changes to the protocol reflecting the change above were made throughout the protocol (Synopsis, Sections 3.1, 4.2, 4.4, 4.5, 4.8, and 6.3, and Table 2).

    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.
    No participant from ‘Inebilizumab /Inebilizumab’ and 1 participant from ‘Placebo/Inebilizumab’ rolled over to SFP. A study period with 0 participants started in any arm is not acceptable (EudraCT limitation); so, not included SFP in ‘Disposition.
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    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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