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    Clinical Trial Results:
    A Phase 2, Randomized Study to Evaluate the Efficacy and Safety of MEDI-546 in Subjects with Systemic Lupus Erythematosus

    Summary
    EudraCT number
    		 2011-004296-36
    Trial protocol
    		 CZ   HU   BG  
    Global end of trial date
    08 Apr 2015

    Results information
    Results version number
    		 v2(current)
    This version publication date
    22 Oct 2016
    First version publication date
    23 Jul 2016
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CD-IA-MEDI-546-1013
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01438489
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    Milstein Building, Granta Park, Cambridge, United Kingdom, CB21 6GH
    Public contact
    Gabor Illei, MD, Senior Director, MedImmune, LLC, +44 3013980000, illeig@Medimmune.com
    Scientific contact
    Gabor Illei, MD, Senior Director, MedImmune, LLC, +44 3013980000, illeig@Medimmune.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
    25 Jun 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Apr 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of anifrolumab compared to placebo at Day 169 (Week 24) in subjects with chronic, moderately to severely active systemic lupus erythematosus (SLE) with an inadequate response to standard of care treatment for SLE.
    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
    		 Participants received background therapy with at least one of the following: oral corticosteroids, antimalarials, azathioprine, methotrexate or mycophenolate. Tapering of oral corticosteroids was allowed after randomization; all other background treatments were continued at stable doses.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Jan 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Brazil: 3
    Country: Number of subjects enrolled
    Bulgaria: 9
    Country: Number of subjects enrolled
    Colombia: 44
    Country: Number of subjects enrolled
    Czech Republic: 3
    Country: Number of subjects enrolled
    Hungary: 10
    Country: Number of subjects enrolled
    India: 3
    Country: Number of subjects enrolled
    Mexico: 16
    Country: Number of subjects enrolled
    Peru: 50
    Country: Number of subjects enrolled
    Poland: 32
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Korea, Republic of: 6
    Country: Number of subjects enrolled
    Taiwan: 12
    Country: Number of subjects enrolled
    Ukraine: 22
    Country: Number of subjects enrolled
    United States: 95
    Worldwide total number of subjects
    307
    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)
    307
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 626 participants were screened out of which 319 participants did not meet eligibility criteria and were considered screen failures, and 307 participants were randomized into the study.

    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
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.
    Arm type
    		 Placebo

    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 received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.

    Arm title
    		 Anifrolumab 300 mg
    Arm description
    		 Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anifrolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Arm title
    		 Anifrolumab 1000 mg
    Arm description
    		 Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anifrolumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Number of subjects in period 1
    		Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Started
    103
    100
    104
    Completed
    77
    84
    85
    Not completed
    26
    16
    19
         Adverse event, serious fatal
    -
    -
    1
         Consent withdrawn by subject
    11
    3
    8
         Subject choice/Subject moved
    2
    1
    1
         Did not complete all 3 follow-up visits
    2
    5
    2
         Inadequate venous access
    -
    2
    -
         Received prohibited medication
    1
    -
    -
         Investigator decision
    -
    1
    -
         Lost to follow-up
    4
    2
    2
         Sponsor decision
    4
    1
    4
         AE/SAEs
    2
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.

    Reporting group title
    Anifrolumab 300 mg
    Reporting group description
    		 Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Reporting group title
    Anifrolumab 1000 mg
    Reporting group description
    		 Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Reporting group values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg Total
    Number of subjects
    		 103 100 104 307
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 103 100 104 307
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    		 39.2 ( 12.9 ) 39.3 ( 12 ) 40.8 ( 11.6 ) -
    Gender, Male/Female
    Units: Participants
        Male
    		 9 6 5 20
        Female
    		 94 94 99 287
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaskan Native
    		 0 4 1 5
        Asian
    		 13 3 6 22
        Black or African American
    		 12 19 10 41
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0
        White
    		 41 36 51 128
        Other
    		 36 37 36 109
        Multiple category checked
    		 1 1 0 2
    Region of Enrollment
    Units: Subjects
        BRAZIL
    		 3 0 0 3
        BULGARIA
    		 3 2 4 9
        COLOMBIA
    		 16 10 18 44
        CZECH REPUBLIC
    		 1 0 2 3
        HUNGARY
    		 2 5 3 10
        INDIA
    		 2 1 0 3
        MEXICO
    		 4 7 5 16
        PERU
    		 15 22 13 50
        POLAND
    		 11 9 12 32
        ROMANIA
    		 1 0 1 2
        SOUTH KOREA
    		 3 0 3 6
        TAIWAN
    		 7 2 3 12
        UKRAINE
    		 7 4 11 22
        UNITED STATES OF AMERICA
    		 28 38 29 95
    Study Specific Characteristics
    Units: Kilogram
        arithmetic mean (standard deviation)
    		 68.08 ( 18.98 ) 69.62 ( 17.09 ) 70.74 ( 17.29 ) -
    Subject analysis sets

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks. One participant from Placebo group received Anifrolumab 1000 mg once in the study and hence, included it in the Anifrolumab 1000 mg group. This subject analysis set is created as per Safety population. The Safety population included all participants who received any dose of investigational product.

    Subject analysis set title
    Anifrolumab 300 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. This subject analysis set is created as per Safety population. The Safety population included all participants who received any dose of investigational product.

    Subject analysis set title
    Anifrolumab 1000 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 1000 mg anifrolumab as an intravenousinfusion every 4 weeks for 48 weeks. One participant from Placebo group received Anifrolumab 1000 mg once in the study and hence, included it in the Anifrolumab 1000 mg group. This subject analysis set is created as per Safety population. The Safety population included all participants who received any dose of investigational product.

    Subject analysis sets values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects
    101
    99
    105
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    101
    99
    105
    Age Continuous |
    Units: Years
        arithmetic mean (standard deviation)
    39.4 ( 12.9 )
    39.1 ( 11.9 )
    40.6 ( 11.6 )
    Gender, Male/Female
    Units: Participants
        Male
    9
    6
    5
        Female
    92
    93
    100
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaskan Native
    0
    4
    1
        Asian
    13
    3
    6
        Black or African American
    11
    19
    11
        Native Hawaiian or Other Pacific Islander
    0
    0
    0
        White
    41
    35
    51
        Other
    35
    37
    36
        Multiple category checked
    1
    1
    0
    Region of Enrollment
    Units: Subjects
        BRAZIL
        BULGARIA
        COLOMBIA
        CZECH REPUBLIC
        HUNGARY
        INDIA
        MEXICO
        PERU
        POLAND
        ROMANIA
        SOUTH KOREA
        TAIWAN
        UKRAINE
        UNITED STATES OF AMERICA
    Study Specific Characteristics
    Units: Kilogram
        arithmetic mean (standard deviation)
    67.66 ( 18.56 )
    69.54 ( 17.15 )
    71.17 ( 17.76 )

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.

    Reporting group title
    Anifrolumab 300 mg
    Reporting group description
    		 Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Reporting group title
    Anifrolumab 1000 mg
    Reporting group description
    		 Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks. One participant from Placebo group received Anifrolumab 1000 mg once in the study and hence, included it in the Anifrolumab 1000 mg group. This subject analysis set is created as per Safety population. The Safety population included all participants who received any dose of investigational product.

    Subject analysis set title
    Anifrolumab 300 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks. This subject analysis set is created as per Safety population. The Safety population included all participants who received any dose of investigational product.

    Subject analysis set title
    Anifrolumab 1000 mg
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants received 1000 mg anifrolumab as an intravenousinfusion every 4 weeks for 48 weeks. One participant from Placebo group received Anifrolumab 1000 mg once in the study and hence, included it in the Anifrolumab 1000 mg group. This subject analysis set is created as per Safety population. The Safety population included all participants who received any dose of investigational product.

    Primary: Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169

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    End point title
    		 Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 169
    End point description
    An SRI (4) responder defined as participant who had 1) reduction in baseline Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of greater than or equal to (>=) 4 points; 2) no worsening of disease from baseline as measured by Physician Global Assessment (MDGA) (worsening was defined as an increase of >= 0.3 from baseline on 0 to 3.0 visual analog scale); 3) no new British Isles Lupus Assessment Group 2004(BILAG-2004) Index ‘A’ organ system score and no more than one new or worsening BILAG-2004 Index ‘B’ organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 [less than 10 milligram per day (mg/day) and less or equal to dose received on Day 1]. SRI was analyzed by logistic regression model. The modified Intent-To-Treat (mITT) included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
    End point type
    Primary
    End point timeframe
    Day 169
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    102
    99
    104
    Units: Percentage of Participants
        number (not applicable)
    17.6
    34.3
    28.8
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    All-comers
    Comparison groups
    Placebo v Anifrolumab 300 mg
    Number of subjects included in analysis
    201
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.014
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.38
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.33
         upper limit
    		 4.26
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    All-comers
    Comparison groups
    Placebo v Anifrolumab 1000 mg
    Number of subjects included in analysis
    206
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.063
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.94
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.08
         upper limit
    		 3.49

    Primary: Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169

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    End point title
    		 Percentage of Type I Interferon (IFN) Test High Participants Achieving an Systemic Lupus Erythematosus Responder Index (SRI) (4) Response With Oral Corticosteroids (OCS) Tapering at Day 169
    End point description
    Type I IFN signature in whole blood assessed by using a 4-gene diagnostic test. Blood samples collected were used to identify participants as IFN test-high. Results of this test were used to stratify participants. An SRI (4) Responder were participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of >= 4 points; 2) no worsening of disease from baseline as measured by Physician Global Assessment (MDGA) (worsening was defined as an increase of >= 0.3 from baseline on 0 to 3.0 visual analog scale); 3) no new BILAG-2004 Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 85 through Day 169 [less than 10 mg/day and less or equal to the dose received on Day 1]. mITT included all randomized participants who received any investigational product and had baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
    End point type
    Primary
    End point timeframe
    Day 169
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    76
    75
    78
    Units: Percentage of Participants
        number (not applicable)
    13.2
    36
    28.2
    Statistical analysis title
    		 Statistical Analysis 2
    Statistical analysis description
    High
    Comparison groups
    Placebo v Anifrolumab 1000 mg
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.029
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.65
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.27
         upper limit
    		 5.53
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    High
    Comparison groups
    Placebo v Anifrolumab 300 mg
    Number of subjects included in analysis
    151
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.004
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.55
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.72
         upper limit
    		 7.32

    Secondary: Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365

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    End point title
    		 Percentage of Participants Achieving an Systemic Lupus Erythematosus (SLE) Responder Index [SRI (4)] Response With Oral Corticosteroids (OCS) Tapering at Day 365
    End point description
    An SRI (4) Responder was defined as a participant who had 1) a reduction in baseline SLEDAI-2K disease activity score of >= 4 points; 2) no worsening of disease from baseline as measured by the MDGA (worsening was defined as an increase of >= 0.3 from baseline on a 0 to 3.0 visual analog scale); and 3) no new British Isles Lupus Assessment Group 2004 (BILAG-2004) Index A organ system score and no more than one new or worsening BILAG-2004 Index B organ system score. OCS tapering requires a sustained reduction of OCS from Day 281 through Day 365 (less than 10 mg/day and less or equal to the dose received on Day 1). SRI was analyzed by a logistic regression model. The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Day 365
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    102
    99
    104
    Units: Percentage of Participants
        number (not applicable)
    25.5
    51.5
    38.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/day of Prednisone or Equivalent at Baseline who Were able to Taper to less than or equal to (<=) 7.5 mg/day at Day 365

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    End point title
    		 Percentage of Participants on Oral Corticosteroids (OCS) >=10 mg/day of Prednisone or Equivalent at Baseline who Were able to Taper to less than or equal to (<=) 7.5 mg/day at Day 365
    End point description
    Participants on OCS >=10 mg/day of prednisone or equivalent at baseline who were able to taper to <= 7.5 mg/day at Day 365 were evaluated. The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Day 365
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    64
    55
    63
    Units: Percentage of Participants
        number (not applicable)
    26.6
    56.4
    31.7
    No statistical analyses for this end point

    Secondary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interest (AESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a study participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A serious AE (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial/prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly (in offspring of participant). AEs may be treatment emergent (TE) [that is, occurring after initial receipt of investigational product] or non-TE. An AESI is one of scientific and medical concern specific to understanding biologics and requires close monitoring and rapid communication by investigator to sponsor. The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) to Day 422 (End of Study)
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    101
    99
    105
    Units: Participants
        TEAEs
    78
    84
    90
        TESAEs
    19
    16
    18
        AESIs
    12
    10
    15
    No statistical analyses for this end point

    Secondary: Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events

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    End point title
    		 Number of Participants With Clinically Significant Laboratory Abnormalities in Investigations Reported as Treatment-Emergent Adverse Events
    End point description
    Any medically significant change in laboratory evaluations were recorded as Treatment emergent adverse events. The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) to Day 422 (End of Study)
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    101
    99
    105
    Units: Participants
        Neutrophil count increased
    0
    1
    3
        Leukocytosis
    0
    1
    2
        Leukopenia
    2
    0
    3
        Neutropenia
    0
    0
    3
        Anaemia
    0
    0
    2
        Iron deficiency anaemia
    0
    1
    1
        Lymphopenia
    0
    0
    2
        Microcytic anaemia
    1
    0
    2
        Thrombocytosis
    0
    1
    0
        White blood cell count increased
    0
    0
    1
        Monocyte count increased
    0
    0
    1
        Hypochromic anaemia
    1
    0
    0
        Hyperglycaemia
    1
    3
    1
        Hypokalaemia
    2
    3
    0
        Hepatic enzyme increased
    1
    0
    3
        Hypocalcaemia
    0
    1
    1
        Lipid metabolism disorder
    0
    1
    1
        Alanine aminotransferase increased
    0
    1
    1
        Aspartate aminotransferase increased
    0
    2
    0
        Blood creatine phosphokinase increased
    0
    1
    1
        Hyperlipidaemia
    1
    0
    1
        Hypertriglyceridaemia
    2
    1
    0
        Hyponatraemia
    0
    0
    1
        Blood alkaline phosphatase increased
    0
    1
    0
        Gamma-glutamyltransferase increased
    0
    1
    0
        Glomerular filtration rate decreased
    0
    1
    0
        Transaminases increased
    1
    0
    1
        Dyslipidaemia
    1
    0
    0
        Alanine aminotransferase abnormal
    1
    0
    0
        Aspartate aminotransferase abnormal
    1
    0
    0
        Blood triglycerides abnormal
    1
    0
    0
        Glomerular filtration rate increased
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants With Vital Signs Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
    End point description
    Vital sign parameters are temperature, blood pressure, respiratory rate, heart rate and weight. Vital signs abnormalities were reported as TEAEs. The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) to Day 422 (End of Study)
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    101
    99
    105
    Units: Participants
        Hypertension
    7
    3
    2
        Pyrexia
    5
    0
    3
        Blood pressure increased
    0
    2
    1
        Blood pressure decreased
    0
    0
    1
        Hypotension
    0
    1
    0
        Secondary hypertension
    0
    0
    1
        Weight increased
    0
    0
    1
        Blood pressure abnormal
    1
    0
    0
        Chills
    1
    0
    0
        Hypertensive emergency
    1
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)
    End point description
    Any medically significant changes from the screening ECG was recorded as TEAEs. An abnormal ECG findings such as QT prolonged were reported as treatment emergent adverse events. The safety population included participants who received any investigational product. Here, "N" signifies evaluable participants for this outcome measure. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
    End point type
    Secondary
    End point timeframe
    Day 1 (Baseline) to Day 422 (End of Study)
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    101
    99
    105
    Units: Participants
    0
    0
    2
    No statistical analyses for this end point

    Secondary: Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)

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    End point title
    		 Percentage of SLE Participants With Positive Anti-drug Antibody (ADA)
    End point description
    Anti-drug antibody responses to anifrolumab in serum were evaluated. The safety population included participants who received any investigational product. Here, "N" and “n” signifies evaluable participants for this outcome measure and for specified category of the arms respectively. One participant from Placebo group received Anifrolumab 1000 mg once and hence, included it in the Anifrolumab 1000 mg group.
    End point type
    Secondary
    End point timeframe
    Days 1, 85, 141, 169, 253, 337 (Treatment Phase), 365, 396, and 422 (Follow-up Period)
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    101
    99
    105
    Units: Percentage of Participants
    number (not applicable)
        Day 1 (n=100,98,105)
    1
    1
    1.9
        Day 85 (n=91,93,98)
    1.1
    0
    0
        Day 141 (n=84,94,93)
    2.4
    0
    2.2
        Day 169 (n=81,89,92)
    2.5
    0
    1.1
        Day 253 (n=72,86,86)
    0
    1.2
    0
        Day 337 (n=70,87,76)
    0
    1.1
    0
        Day 365 (n=85,96,94)
    0
    1
    1.1
        Day 396 (n=78,88,90)
    0
    2.3
    0
        Day 422 (n=76,86,77)
    1.3
    5.8
    0
        Any Visit Post Baseline (n= 99,98,102)
    3
    5.1
    2
    No statistical analyses for this end point

    Secondary: Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature

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    End point title
    		 Neutralization Ratio of 21-Gene Type I Interferon (IFN) Signature for Participants With Positive Baseline Pharmacodynamic (PD) Gene Signature
    End point description
    The PD positive and negative gene signature was determined by comparing the expression of type I IFN-inducible genes in a 21-gene panel in study participants relative to pooled normal blood collected from healthy participants. The mITT population included all randomized participants who received any investigational product and had a baseline primary efficacy measurement. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
    End point type
    Secondary
    End point timeframe
    Days 29, 85, 141, 169, 253, 337 (treatment phase), on Days 365, 396, and 422 (follow up period)
    End point values
    		 Placebo Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    102
    99
    104
    Units: Ratio
    arithmetic mean (standard deviation)
        Day 29 (n= 68, 66, 73)
    -0.753 ( 44.678 )
    70.194 ( 40.028 )
    82.056 ( 16.108 )
        Day 85 (n= 63, 62, 72)
    -5.412 ( 44.354 )
    72.639 ( 34.443 )
    79.35 ( 40.428 )
        Day 141 (n= 59, 64, 68)
    -25.411 ( 78.391 )
    73.662 ( 36.684 )
    88.569 ( 10.364 )
        Day 169 (n= 56, 60, 66)
    -17.122 ( 67.603 )
    77.364 ( 30.733 )
    88.126 ( 10.278 )
        Day 253 (n= 50, 60, 61)
    -9.908 ( 49.826 )
    73.972 ( 41.267 )
    86.099 ( 15.615 )
        Day 337 (n= 49, 59, 53)
    -13.784 ( 45.541 )
    79.363 ( 28.803 )
    87.811 ( 8.41 )
        Day 365 (n= 58, 66, 68)
    -6.428 ( 50.358 )
    72.796 ( 35.552 )
    81.115 ( 53.121 )
        Day 396 (n= 56, 61, 64)
    -22.106 ( 64.529 )
    11.51 ( 56.385 )
    72.291 ( 31.182 )
        Day 422 (n= 53, 57, 55)
    -31.777 ( 70.173 )
    -0.836 ( 44.596 )
    37.532 ( 66.339 )
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Anifrolumab at Day 1, 169 and 337 [1]
    End point description
    Maximum plasma concentration (Cmax) was defined as the peak plasma level of anifrolumab, derived from plasma concentration ­time data. The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and 15 minutes post-infusion on Day 1, 169 and 337
    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: No statistical analyses for this end point
    End point values
    		 Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    98
    104
    Units: micrograms/milliliter (mcg/mL)
    arithmetic mean (standard deviation)
        Day 1 (n=98,104)
    82.8 ( 64.5 )
    248 ( 79.9 )
        Day 169 (n=86,87)
    110 ( 63.7 )
    375 ( 137 )
        Day 337 (n=83,67)
    127 ( 64.6 )
    439 ( 140 )
    No statistical analyses for this end point

    Secondary: Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab

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    End point title
    		 Accumulation Ratio of Maximum Observed Plasma Concentration (Cmax,AR) of Anifrolumab [2]
    End point description
    Accumulation ratio for maximum plasma concentration (Cmax,AR) of anifrolumab after multiple administration at Day 169 and 337 was calculated. The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and 15 minutes post-infusion on Day 169 and 337
    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: No statistical analyses for this end point
    End point values
    		 Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    81
    86
    Units: Ratio
    median (full range (min-max))
        Day 169 (n=81,86)
    1.36 (0.0367 to 3680)
    1.43 (0.211 to 191)
        Day 337 (n=78,66)
    1.56 (0.132 to 7050)
    1.76 (0.492 to 240)
    No statistical analyses for this end point

    Secondary: Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365

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    End point title
    		 Trough Concentration (Ctrough) of Anifrolumab at Day 29, 169 and 365 [3]
    End point description
    Trough concentration (Ctrough) of anifrolumab at Day 29, 169 and 365 were calculated. The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and 15 minutes post-infusion on Day 29, 169 and 365
    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: No statistical analyses for this end point
    End point values
    		 Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    95
    99
    Units: microgram per milliliter
    arithmetic mean (standard deviation)
        Day 29 (n=95,99)
    7.95 ( 6.17 )
    46.8 ( 24.6 )
        Day 169 (n=87,87)
    18.4 ( 12.9 )
    110 ( 60.5 )
        Day 365 (n=83,71)
    23.6 ( 15.5 )
    154 ( 89.2 )
    No statistical analyses for this end point

    Secondary: Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365

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    End point title
    		 Accumulation Ratio of Trough Concentration (Ctrough,AR) of Anifrolumab at Day 169 and 365 [4]
    End point description
    Accumulation ratio for trough concentration (Ctrough,AR) of anifrolumab after multiple administration at Day 169 and 365 was calculated. The Pharmacokinetic population included all treated participants with at least 1 Pharmacokinetic assessment. Here, "N" signifies evaluable participants for this outcome measure and "n" signifies evaluable participants for the specified category of the arms respectively.
    End point type
    Secondary
    End point timeframe
    Pre-infusion and 15 minutes post-infusion on Day 169 and 365
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analyses for this end point
    End point values
    		 Anifrolumab 300 mg Anifrolumab 1000 mg
    Number of subjects analysed
    82
    86
    Units: Ratio
    median (full range (min-max))
        Day 169 (n=82,86)
    2.49 (0.0599 to 1250)
    2.29 (0.299 to 30.1)
        Day 365 (n=79,70)
    3.06 (0.00816 to 1130)
    3.02 (0.672 to 11.7)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 (Baseline) to Day 422 (End of Study)
    Adverse event reporting additional description
    1 participant from placebo arm inadvertently received one dose of anifrolumab 1000 milligram (mg).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matched to anifrolumab intravenous (IV) infusion every 4 weeks for 48 weeks.

    Reporting group title
    Anifrolumab 1000 mg
    Reporting group description
    		 Participants received 1000 mg anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Reporting group title
    Anifrolumab 300 mg
    Reporting group description
    		 Participants received 300 milligram (mg) anifrolumab as an intravenous infusion every 4 weeks for 48 weeks.

    Serious adverse events
    		 Placebo Anifrolumab 1000 mg Anifrolumab 300 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 101 (18.81%)
    18 / 105 (17.14%)
    16 / 99 (16.16%)
         number of deaths (all causes)
    0
    1
    0
         number of deaths resulting from adverse events
    0
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive ductal breast carcinoma
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 101 (0.99%)
    1 / 105 (0.95%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypertensive emergency
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Secondary hypertension
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vasculitis
         subjects affected / exposed
    2 / 101 (1.98%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 101 (0.99%)
    3 / 105 (2.86%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hand fracture
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac tamponade
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 101 (0.99%)
    2 / 105 (1.90%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 101 (1.98%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myelitis transverse
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal disorder
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Oedematous kidney
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Systemic lupus erythematosus
         subjects affected / exposed
    6 / 101 (5.94%)
    3 / 105 (2.86%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 101 (0.00%)
    1 / 105 (0.95%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lobar pneumonia
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis cryptococcal
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 101 (1.98%)
    2 / 105 (1.90%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 101 (0.99%)
    0 / 105 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 101 (0.00%)
    0 / 105 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Anifrolumab 1000 mg Anifrolumab 300 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    36 / 101 (35.64%)
    46 / 105 (43.81%)
    40 / 99 (40.40%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    13 / 101 (12.87%)
    12 / 105 (11.43%)
    12 / 99 (12.12%)
         occurrences all number
    21
    17
    14
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    4 / 101 (3.96%)
    8 / 105 (7.62%)
    4 / 99 (4.04%)
         occurrences all number
    4
    8
    5
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    4 / 101 (3.96%)
    9 / 105 (8.57%)
    7 / 99 (7.07%)
         occurrences all number
    4
    11
    7
    Nasopharyngitis
         subjects affected / exposed
    4 / 101 (3.96%)
    12 / 105 (11.43%)
    12 / 99 (12.12%)
         occurrences all number
    4
    20
    15
    Upper respiratory tract infection
         subjects affected / exposed
    10 / 101 (9.90%)
    11 / 105 (10.48%)
    12 / 99 (12.12%)
         occurrences all number
    13
    20
    14
    Urinary tract infection
         subjects affected / exposed
    11 / 101 (10.89%)
    7 / 105 (6.67%)
    15 / 99 (15.15%)
         occurrences all number
    18
    12
    16

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Sep 2013
    1. Revised text to include the blinding criteria for study site personnel and subjects in Stage I analysis. 2. Corrected the definition of Grade 4 (life threatening) AEs/SAEs to remove reference to disabilities.
    09 Dec 2014
    1. Revised the numbering of inclusion and exclusion criteria. 2. Revised exclusion criterion 24 to change the HBV DNA levels to qualify and remain in the study from “undetectable as per central lab” to “≤ 169 copies/mL (29 IU/mL) as per central laboratory”. 3. Revised to specify that an unblinded interim analysis is planned for the study. Also added that this analysis will be performed by a limited number of sponsor personnel not involved in the conduct of the study. 4. Revised text to describe the criteria for unblinded staged analyses across Stages I, II, and III. 5. Removed reference to ethylene polyvinyl acetate. 6. Added section header for the followup study and subsequent sections were renumbered. 7. Replaced MedImmune Safety Monitoring Committee with the MedImmune/AstraZeneca safety review committee. 8. Revised section to describe the planned interim analysis. The description for Stage I, II, and III analyses was modified. 9. Removed reference to twosided Type 1 error rate of 0.05 in Sample Size and Power Calculations, Overall Population, and Diagnosticpositive Subpopulation. 10. Increased the sample size of diagnosticpositive subjects per treatment group from 60 to 80.

    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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