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    Clinical Trial Results:
    A Multicentre, Randomised, Double-blind, Placebo-Controlled Phase III Extension Study to Characterise the Long-term Safety and Tolerability of Anifrolumab in Adult Patients with Active Systemic Lupus Erythematosus

    Summary
    EudraCT number
    		 2016-000625-39
    Trial protocol
    		 HU   DE   ES   LT   BG  
    Global end of trial date
    21 Dec 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Jan 2023
    First version publication date
    04 Jan 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    D3461C00009
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02794285
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca
    Sponsor organisation address
    Astraalléen, Södertälje, Sweden, SE-151 85
    Public contact
    Global Clinical Lead, AstraZeneca, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca, +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
    21 Dec 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    21 Dec 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to characterise the long-term safety and tolerability of intravenous (IV) anifrolumab.
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Conference of Harmonisation/Good Clinical Practice, applicable regulatory requirements and the AstraZeneca policy on Bioethics.
    Background therapy
    		 Whereas the background standard of care had to remain stable throughout Phase III feeder studies (D3461C00004 [NCT02446899] or D3461C00005 [NCT02446912]). Investigators were allowed to change dose or add new background immunosuppressants as clinically indicated (with certain exceptions e.g., cyclophosphamide and other biologics that were not permitted). In addition, oral corticosteroid (OCS) and antimalarials could be changed.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    30 Jun 2016
    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
    Argentina: 9
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Bulgaria: 3
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Chile: 7
    Country: Number of subjects enrolled
    Colombia: 4
    Country: Number of subjects enrolled
    France: 9
    Country: Number of subjects enrolled
    Germany: 13
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Israel: 8
    Country: Number of subjects enrolled
    Japan: 33
    Country: Number of subjects enrolled
    Lithuania: 18
    Country: Number of subjects enrolled
    Mexico: 29
    Country: Number of subjects enrolled
    Peru: 22
    Country: Number of subjects enrolled
    Poland: 52
    Country: Number of subjects enrolled
    Romania: 20
    Country: Number of subjects enrolled
    Russian Federation: 14
    Country: Number of subjects enrolled
    South Africa: 8
    Country: Number of subjects enrolled
    Korea, Republic of: 12
    Country: Number of subjects enrolled
    Spain: 13
    Country: Number of subjects enrolled
    Taiwan: 9
    Country: Number of subjects enrolled
    Ukraine: 25
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    United States: 203
    Worldwide total number of subjects
    547
    EEA total number of subjects
    143
    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)
    530
    From 65 to 84 years
    17
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This long-term extension (LTE) study was conducted at 176 study centres in 24 countries.

    Pre-assignment
    Screening details
    		 The LTE population was comprised of participants who had completed the 52-week double-blind treatment period in one of the Phase III feeder studies (D3461C00004 [NCT02446899] or D3461C00005 [NCT02446912]), met all LTE eligibility criteria, and were willing to continue into the extension 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, Carer, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Randomised Anifrolumab 300 mg
    Arm description
    		 Anifrolumab (300 mg) administered via an intravenous (IV) infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anifrolumab
    Investigational medicinal product code
    MEDI-546
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered as an IV infusion via an infusion pump over a minimum of 30 minutes.

    Arm title
    		 Placebo Feeder + Placebo LTE
    Arm description
    		 Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
    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
    Administered as an IV infusion via an infusion pump over a minimum of 30 minutes.

    Arm title
    		 Placebo Feeder + Anifrolumab 300 mg LTE
    Arm description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anifrolumab
    Investigational medicinal product code
    MEDI-546
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered as an IV infusion via an infusion pump over a minimum of 30 minutes.

    Arm title
    		 Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Arm description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anifrolumab
    Investigational medicinal product code
    MEDI-546
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Administered as an IV infusion via an infusion pump over a minimum of 30 minutes.

    Number of subjects in period 1
    		Randomised Anifrolumab 300 mg Placebo Feeder + Placebo LTE Placebo Feeder + Anifrolumab 300 mg LTE Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Started
    257
    112
    111
    67
    Completed
    178
    54
    69
    41
    Not completed
    79
    58
    42
    26
         Adverse event, serious fatal
    2
    1
    2
    -
         Severe Non-compliance to Protocol
    1
    2
    1
    -
         Condition Under Investigation Worsened
    -
    2
    1
    -
         Failure to Meet Randomisation Criteria
    -
    -
    1
    -
         Other - Not Due to COVID-19 Pandemic
    2
    6
    2
    1
         Missing
    1
    -
    -
    -
         Development of Study-specific Withdrawal Criteria
    1
    -
    -
    1
         Consent withdrawn by subject
    38
    29
    20
    12
         Adverse event, non-fatal
    11
    4
    5
    8
         Lost to follow-up
    5
    6
    3
    1
         Due to COVID-19 Pandemic
    7
    2
    4
    -
         Condition Under Investigation Improved
    1
    -
    -
    -
         Lack of efficacy
    10
    6
    3
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Randomised Anifrolumab 300 mg
    Reporting group description
    		 Anifrolumab (300 mg) administered via an intravenous (IV) infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.

    Reporting group title
    Placebo Feeder + Placebo LTE
    Reporting group description
    		 Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.

    Reporting group title
    Placebo Feeder + Anifrolumab 300 mg LTE
    Reporting group description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.

    Reporting group title
    Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Reporting group description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

    Reporting group values
    		 Randomised Anifrolumab 300 mg Placebo Feeder + Placebo LTE Placebo Feeder + Anifrolumab 300 mg LTE Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE Total
    Number of subjects
    		 257 112 111 67 547
    Age Categorical
    Units:
        <=18 years
    		 0 0 0 0 0
        Between 18 and 65 years
    		 247 111 107 65 530
        >=65 years
    		 10 1 4 2 17
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 43.4 ( 11.51 ) 41.4 ( 11.46 ) 42.2 ( 12.24 ) 42.4 ( 11.70 ) -
    Sex: Female, Male
    Units:
        Female
    		 237 103 102 63 505
        Male
    		 20 9 9 4 42
    Race
    Units: Subjects
        White
    		 173 77 70 45 365
        Black or African American
    		 28 11 17 10 66
        Asian
    		 33 10 12 6 61
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0
        American Indian or Alaska Native
    		 3 1 0 0 4
        Other
    		 15 11 10 6 42
        Missing
    		 5 2 2 0 9
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 54 28 22 14 118
        Not Hispanic or Latino
    		 198 82 87 53 420
        Missing
    		 5 2 2 0 9

    End points

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    End points reporting groups
    Reporting group title
    Randomised Anifrolumab 300 mg
    Reporting group description
    		 Anifrolumab (300 mg) administered via an intravenous (IV) infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.

    Reporting group title
    Placebo Feeder + Placebo LTE
    Reporting group description
    		 Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.

    Reporting group title
    Placebo Feeder + Anifrolumab 300 mg LTE
    Reporting group description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.

    Reporting group title
    Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Reporting group description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

    Primary: Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs)

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    End point title
    		 Exposure-adjusted Incidence Rates (EAIRs) of Adverse Events of Special Interest (AESIs) [1]
    End point description
    The event rate per 100 participant years was defined as the number of participants with an event divided by the sum of exposure time during the LTE study (including follow-up) in days for all participants in the analysis set multiplied by 365.25 days/year multiplied by 100. The exposure in a time period for each participant was calculated as end of period - start of period + 1. EAIRs of AESIs are presented as event rate per 100 participant years. The following AESIs were pre-defined: - Non-opportunistic serious infections - Opportunistic infections - Anaphylaxis - Malignancy - Herpes zoster - Tuberculosis (TB) (including latent TB) - Influenza - Vasculitis (non-systemic lupus erythematosus [SLE]) - Major cardiovascular events as according to the Cardiovascular Event Adjudication Committee. Full analysis set (FAS) - LTE Study: consist of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.
    End point type
    Primary
    End point timeframe
    Up to a maximum of 1114 days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No additional statistical analysis was pre-specified for this end point.
    End point values
    		 Randomised Anifrolumab 300 mg Placebo Feeder + Placebo LTE Placebo Feeder + Anifrolumab 300 mg LTE Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Number of subjects analysed
    257
    112
    111
    67
    Units: Events per 100 participant years
        number (not applicable)
    11.0
    9.6
    12.9
    12.5
    No statistical analyses for this end point

    Primary: EAIRs of Serious Adverse Events (SAEs)

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    End point title
    		 EAIRs of Serious Adverse Events (SAEs) [2]
    End point description
    EAIRs of SAEs are presented as event rate per 100 participant years. An SAE was an AE occurring during any study phase that fulfils 1 or more of the following criteria: - Results in death - Is immediately life-threatening - Requires in-patient hospitalisation or prolongation of existing hospitalisation - Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions - Is a congenital abnormality or birth defect - Is an important medical event that may jeopardise the participant or may require medical intervention to prevent one of the outcomes listed above. FAS - LTE Study: consist of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.
    End point type
    Primary
    End point timeframe
    Up to a maximum of 1114 days
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No additional statistical analysis was pre-specified for this end point.
    End point values
    		 Randomised Anifrolumab 300 mg Placebo Feeder + Placebo LTE Placebo Feeder + Anifrolumab 300 mg LTE Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Number of subjects analysed
    257
    112
    111
    67
    Units: Events per 100 participant years
        number (not applicable)
    8.5
    11.2
    10.1
    10.7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Day 1 up to until follow-up visit 2 (Week 164)
    Adverse event reporting additional description
    FAS - LTE Study: consist of all participants who were randomised and received at least 1 dose of investigational product in the LTE Study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Randomised Anifrolumab 300 mg
    Reporting group description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (300 mg) in a feeder study.

    Reporting group title
    Placebo Feeder + Placebo LTE
    Reporting group description
    		 Placebo administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.

    Reporting group title
    Placebo Feeder + Anifrolumab 300 mg LTE
    Reporting group description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered placebo in a feeder study.

    Reporting group title
    Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Reporting group description
    		 Anifrolumab (300 mg) administered via an IV infusion every 4 weeks for up to 152 weeks (39 doses). Participants were previously administered anifrolumab (150 mg) in a feeder study.

    Serious adverse events
    		 Randomised Anifrolumab 300 mg Placebo Feeder + Placebo LTE Placebo Feeder + Anifrolumab 300 mg LTE Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Total subjects affected by serious adverse events
         subjects affected / exposed
    56 / 257 (21.79%)
    27 / 112 (24.11%)
    26 / 111 (23.42%)
    14 / 67 (20.90%)
         number of deaths (all causes)
    3
    1
    3
    2
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Malignant hypertension
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Venous thrombosis limb
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chest discomfort
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Incarcerated hernia
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mucosal haemorrhage
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine haemorrhage
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical dysplasia
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heavy menstrual bleeding
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst ruptured
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterovaginal prolapse
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 112 (0.89%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Affect lability
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    International normalised ratio increased
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Humerus fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthropod bite
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periprocedural myocardial infarction
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial ischaemia
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post herpetic neuralgia
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial aneurysm
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Central nervous system lupus
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    1 / 111 (0.90%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    2 / 257 (0.78%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoperitoneum
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth impacted
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 257 (0.78%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Systemic lupus erythematosus
         subjects affected / exposed
    6 / 257 (2.33%)
    6 / 112 (5.36%)
    1 / 111 (0.90%)
    2 / 67 (2.99%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 8
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Arthritis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Synovial cyst
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tenosynovitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Herpes zoster
         subjects affected / exposed
    6 / 257 (2.33%)
    1 / 112 (0.89%)
    3 / 111 (2.70%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    3 / 6
    1 / 1
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    6 / 257 (2.33%)
    2 / 112 (1.79%)
    3 / 111 (2.70%)
    3 / 67 (4.48%)
         occurrences causally related to treatment / all
    0 / 6
    1 / 2
    0 / 3
    3 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    COVID-19
    Additional description: Only participants who were ongoing in the trial at the time the COVID-19 pandemic started are included. All participants who had completed or discontinued the trial prior to the pandemic are excluded from number of participants at risk.
         subjects affected / exposed [1]
    4 / 201 (1.99%)
    0 / 64 (0.00%)
    2 / 82 (2.44%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
    COVID-19 pneumonia
    Additional description: Only participants who were ongoing in the trial at the time the COVID-19 pandemic started are included. All participants who had completed or discontinued the trial prior to the pandemic are excluded from number of participants at risk.
         subjects affected / exposed [2]
    3 / 201 (1.49%)
    1 / 64 (1.56%)
    3 / 82 (3.66%)
    0 / 42 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 1
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    3 / 257 (1.17%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 257 (0.78%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 257 (0.39%)
    1 / 112 (0.89%)
    2 / 111 (1.80%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster disseminated
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic inflammatory disease
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Streptococcal urinary tract infection
         subjects affected / exposed
    1 / 257 (0.39%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    2 / 111 (1.80%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis staphylococcal
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster meningitis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ludwig angina
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mediastinitis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parotitis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia staphylococcal
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative abscess
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    1 / 111 (0.90%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    0 / 257 (0.00%)
    1 / 112 (0.89%)
    0 / 111 (0.00%)
    0 / 67 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 257 (0.00%)
    0 / 112 (0.00%)
    0 / 111 (0.00%)
    1 / 67 (1.49%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Only participants who were ongoing in the trial at the time the COVID-19 pandemic started are included. All participants who had completed or discontinued the trial prior to the pandemic are excluded from number of participants at risk.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed to this adverse event. These numbers are expected to be equal.
    Justification: Only participants who were ongoing in the trial at the time the COVID-19 pandemic started are included. All participants who had completed or discontinued the trial prior to the pandemic are excluded from number of participants at risk.
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Randomised Anifrolumab 300 mg Placebo Feeder + Placebo LTE Placebo Feeder + Anifrolumab 300 mg LTE Anifrolumab 150 mg Feeder + Anifrolumab 300 mg LTE
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    195 / 257 (75.88%)
    79 / 112 (70.54%)
    81 / 111 (72.97%)
    53 / 67 (79.10%)
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    17 / 257 (6.61%)
    6 / 112 (5.36%)
    8 / 111 (7.21%)
    2 / 67 (2.99%)
         occurrences all number
    28
    10
    13
    9
    Fall
         subjects affected / exposed
    11 / 257 (4.28%)
    6 / 112 (5.36%)
    4 / 111 (3.60%)
    3 / 67 (4.48%)
         occurrences all number
    15
    8
    5
    5
    Contusion
         subjects affected / exposed
    10 / 257 (3.89%)
    3 / 112 (2.68%)
    7 / 111 (6.31%)
    6 / 67 (8.96%)
         occurrences all number
    12
    3
    8
    8
    Vascular disorders
    Hypertension
         subjects affected / exposed
    13 / 257 (5.06%)
    4 / 112 (3.57%)
    4 / 111 (3.60%)
    3 / 67 (4.48%)
         occurrences all number
    17
    4
    4
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    28 / 257 (10.89%)
    11 / 112 (9.82%)
    7 / 111 (6.31%)
    10 / 67 (14.93%)
         occurrences all number
    35
    14
    13
    11
    Dizziness
         subjects affected / exposed
    8 / 257 (3.11%)
    3 / 112 (2.68%)
    4 / 111 (3.60%)
    4 / 67 (5.97%)
         occurrences all number
    9
    3
    6
    4
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    18 / 257 (7.00%)
    6 / 112 (5.36%)
    8 / 111 (7.21%)
    5 / 67 (7.46%)
         occurrences all number
    21
    7
    9
    11
    Nausea
         subjects affected / exposed
    12 / 257 (4.67%)
    7 / 112 (6.25%)
    6 / 111 (5.41%)
    2 / 67 (2.99%)
         occurrences all number
    16
    8
    9
    2
    Abdominal pain upper
         subjects affected / exposed
    7 / 257 (2.72%)
    2 / 112 (1.79%)
    5 / 111 (4.50%)
    4 / 67 (5.97%)
         occurrences all number
    7
    2
    6
    4
    Constipation
         subjects affected / exposed
    7 / 257 (2.72%)
    7 / 112 (6.25%)
    3 / 111 (2.70%)
    0 / 67 (0.00%)
         occurrences all number
    7
    9
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    18 / 257 (7.00%)
    4 / 112 (3.57%)
    4 / 111 (3.60%)
    7 / 67 (10.45%)
         occurrences all number
    19
    4
    4
    9
    Psychiatric disorders
    Depression
         subjects affected / exposed
    9 / 257 (3.50%)
    4 / 112 (3.57%)
    3 / 111 (2.70%)
    4 / 67 (5.97%)
         occurrences all number
    9
    4
    3
    4
    Insomnia
         subjects affected / exposed
    8 / 257 (3.11%)
    3 / 112 (2.68%)
    5 / 111 (4.50%)
    7 / 67 (10.45%)
         occurrences all number
    9
    3
    7
    7
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    21 / 257 (8.17%)
    9 / 112 (8.04%)
    11 / 111 (9.91%)
    3 / 67 (4.48%)
         occurrences all number
    28
    10
    13
    6
    Back pain
         subjects affected / exposed
    18 / 257 (7.00%)
    10 / 112 (8.93%)
    12 / 111 (10.81%)
    9 / 67 (13.43%)
         occurrences all number
    21
    12
    15
    12
    Systemic lupus erythematosus
         subjects affected / exposed
    12 / 257 (4.67%)
    2 / 112 (1.79%)
    3 / 111 (2.70%)
    5 / 67 (7.46%)
         occurrences all number
    17
    2
    3
    6
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    57 / 257 (22.18%)
    16 / 112 (14.29%)
    18 / 111 (16.22%)
    9 / 67 (13.43%)
         occurrences all number
    71
    21
    27
    12
    Nasopharyngitis
         subjects affected / exposed
    63 / 257 (24.51%)
    13 / 112 (11.61%)
    29 / 111 (26.13%)
    15 / 67 (22.39%)
         occurrences all number
    139
    33
    48
    24
    Upper respiratory tract infection
         subjects affected / exposed
    55 / 257 (21.40%)
    18 / 112 (16.07%)
    22 / 111 (19.82%)
    8 / 67 (11.94%)
         occurrences all number
    95
    24
    41
    14
    Bronchitis
         subjects affected / exposed
    41 / 257 (15.95%)
    9 / 112 (8.04%)
    17 / 111 (15.32%)
    16 / 67 (23.88%)
         occurrences all number
    56
    9
    24
    19
    Pharyngitis
         subjects affected / exposed
    20 / 257 (7.78%)
    5 / 112 (4.46%)
    12 / 111 (10.81%)
    9 / 67 (13.43%)
         occurrences all number
    29
    5
    18
    11
    Sinusitis
         subjects affected / exposed
    24 / 257 (9.34%)
    3 / 112 (2.68%)
    9 / 111 (8.11%)
    6 / 67 (8.96%)
         occurrences all number
    29
    3
    15
    7
    Oral herpes
         subjects affected / exposed
    19 / 257 (7.39%)
    6 / 112 (5.36%)
    6 / 111 (5.41%)
    0 / 67 (0.00%)
         occurrences all number
    33
    8
    8
    0
    Herpes zoster
         subjects affected / exposed
    16 / 257 (6.23%)
    6 / 112 (5.36%)
    12 / 111 (10.81%)
    10 / 67 (14.93%)
         occurrences all number
    18
    6
    12
    10
    Latent tuberculosis
         subjects affected / exposed
    16 / 257 (6.23%)
    2 / 112 (1.79%)
    4 / 111 (3.60%)
    1 / 67 (1.49%)
         occurrences all number
    16
    2
    4
    1
    Influenza
         subjects affected / exposed
    14 / 257 (5.45%)
    5 / 112 (4.46%)
    9 / 111 (8.11%)
    5 / 67 (7.46%)
         occurrences all number
    14
    5
    9
    5
    Gastroenteritis
         subjects affected / exposed
    7 / 257 (2.72%)
    7 / 112 (6.25%)
    13 / 111 (11.71%)
    3 / 67 (4.48%)
         occurrences all number
    9
    9
    17
    3

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 May 2016
    - Removed requirement that female participants with an intact cervix must have documentation of a Pap smear with no documented malignancy before Day 1/Visit 1 and yearly thereafter. - Previous use (within the last 60 days) of mizoribine > 150 mg/day has been added as an exclusion criterion. - Added requirement that human immunodeficiency virus status must be confirmed by a test performed by the central laboratory if not tested in feeder studies.
    10 Aug 2017
    - Added requirement that females with an intact cervix must have a Pap smear without documented malignancy. Added that all female participants with an intact cervix should have a Pap smear performed within 3 months of the last investigational product dose, e.g., at the end of study or at the early discontinuation. visit. - The requirement for QuantiFERON® (QFT) testing for cases where newly indeterminate QFT test results are obtained was added. The QFT testing for tuberculosis was added to the list of assessments to be performed at the Early Discontinuation Visit. - Mizoribine was added to the list of permitted immunosuppressants. - Mycophenolic acid was added to the list of permitted immunosuppressants in the Protocol synopsis and the dose of mycophenolic acid not to be exceeded was updated to > 1.44 g/day. - Baricitinib, tofacitinib, or other Janus kinase inhibitors were added to the list of prohibited concomitant medications. - Updates were made to the permitted and prohibited medications. Topical retinoids were removed from the list of prohibited medications. - Serum chemistry, haematology and urinalysis sampling were added to Visit 3/Week 8 and Visit 10/Week 36.

    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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