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    Clinical Trial Results:
    A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in Adults with Systemic Lupus Erythematosus

    Summary
    EudraCT number
    2012-004619-30
    Trial protocol
    CZ   HU   BG  
    Global end of trial date
    18 Jul 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    17 Jul 2019
    First version publication date
    17 Jul 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CD-IA-MEDI-546-1145
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01753193
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    MedImmune Way, Gaithersburg, Maryland, United States, 20878
    Public contact
    Raj Tummala, MedImmune, LLC, +1 301-398-0548, information.center@astrazeneca.com
    Scientific contact
    Raj Tummala, MedImmune, LLC, +1 301-398-0548, 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 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Jul 2018
    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 long-term safety and tolerability of intravenous (IV) MEDI-546 in adult participants with moderately-to-severely active systemic lupus erythematosus (SLE).
    Protection of trial subjects
    The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    28 Mar 2013
    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
    Poland: 28
    Country: Number of subjects enrolled
    Hungary: 3
    Country: Number of subjects enrolled
    United States: 67
    Country: Number of subjects enrolled
    Taiwan: 6
    Country: Number of subjects enrolled
    Romania: 1
    Country: Number of subjects enrolled
    Czech Republic: 3
    Country: Number of subjects enrolled
    Bulgaria: 7
    Country: Number of subjects enrolled
    Peru: 40
    Country: Number of subjects enrolled
    Ukraine: 9
    Country: Number of subjects enrolled
    Korea, Republic of: 5
    Country: Number of subjects enrolled
    Brazil: 2
    Country: Number of subjects enrolled
    Colombia: 34
    Country: Number of subjects enrolled
    Mexico: 13
    Worldwide total number of subjects
    218
    EEA total number of subjects
    42
    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)
    210
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted from 28 Mar 2013 to 18 Jul 2018.

    Pre-assignment
    Screening details
    A total of 218 participants were enrolled in this open-label extension (OLE) study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Anifrolumab
    Arm description
    Participants received intravenous (IV) infusion of anifrolumab (MEDI-546) 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter received 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.
    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
    Intravenous (IV) infusion of anifrolumab (MEDI-546) 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12- Feb-2015 (approval of protocol amendment 4); and thereafter 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.

    Number of subjects in period 1
    Anifrolumab
    Started
    218
    Completed
    172
    Not completed
    46
         Adverse event, serious fatal
    1
         Unspecified
    16
         Consent withdrawn by subject
    23
         Lost to follow-up
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Anifrolumab
    Reporting group description
    Participants received intravenous (IV) infusion of anifrolumab (MEDI-546) 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter received 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.

    Reporting group values
    Anifrolumab Total
    Number of subjects
    218 218
    Age categorical
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    210 210
        From 65-84 years
    8 8
        85 years and over
    0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    40.8 ± 12.2 -
    Sex: Female, Male
    Units: Subjects
        Male
    15 15
        Female
    203 203
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    104 104
        Not Hispanic or Latino
    114 114
        Unknown or Not Reported
    0 0
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    4 4
        Asian
    11 11
        Native Hawaiian or Other Pacific Islander
    0 0
        Black or African American
    29 29
        White
    87 87
        More than one race
    2 2
        Unknown or Not Reported
    85 85

    End points

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    End points reporting groups
    Reporting group title
    Anifrolumab
    Reporting group description
    Participants received intravenous (IV) infusion of anifrolumab (MEDI-546) 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter received 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.

    Primary: Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

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    End point title
    Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [1]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study.
    End point type
    Primary
    End point timeframe
    From first dose of study drug (Day 1) through 168 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    Anifrolumab
    Number of subjects analysed
    218
    Units: Participants
        TEAEs
    170
        TESAEs
    50
    No statistical analyses for this end point

    Primary: Number of Participants With Adverse Events Resulting in Discontinuation (DAEs) of Anifrolumab

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    End point title
    Number of Participants With Adverse Events Resulting in Discontinuation (DAEs) of Anifrolumab [2]
    End point description
    Number of participants with DAEs are reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study.
    End point type
    Primary
    End point timeframe
    From first dose of study drug (Day 1) through 168 weeks
    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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    Anifrolumab
    Number of subjects analysed
    218
    Units: Participants
    17
    No statistical analyses for this end point

    Primary: Number of Participants With Adverse Events of Special Interest (AESIs)

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    End point title
    Number of Participants With Adverse Events of Special Interest (AESIs) [3]
    End point description
    An AESI is scientific and medical concern specific to understanding of the study drug. An AESI may be serious or non-serious. Number of participants with AESIs are reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study.
    End point type
    Primary
    End point timeframe
    From first dose of study drug (Day 1) through 168 weeks
    Notes
    [3] - 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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
    End point values
    Anifrolumab
    Number of subjects analysed
    218
    Units: Participants
        Herpes zoster
    11
        Drug hypersensitivity
    1
        Hypersensitivity
    2
        Infusion related reaction
    4
        Nausea
    1
        Hodgkin's disease
    1
        Latent tuberculosis
    5
        Hypersensitivity vasculitis
    1
        Vasculitis
    1
    No statistical analyses for this end point

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

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    End point title
    Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Anifrolumab
    End point description
    The number of participants with positive serum antibodies to anifrolumab at anytime (including baseline) are reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study. Participants with reportable ADA titer results were analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-dose on Day 1) up to Week 168
    End point values
    Anifrolumab
    Number of subjects analysed
    216
    Units: Participants
    5
    No statistical analyses for this end point

    Secondary: Anti-Drug Antibodies (ADA) Titer to Anifrolumab

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    End point title
    Anti-Drug Antibodies (ADA) Titer to Anifrolumab
    End point description
    Median ADA titer in participants with ADA-positive assessments and reportable ADA titer results are reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study. Only participants who had ADA-positive assessments with reportable ADA titer results were analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-dose on Day 1) up to Week 168
    End point values
    Anifrolumab
    Number of subjects analysed
    5
    Units: Antibody titers
        median (full range (min-max))
    120 (30 to 120)
    No statistical analyses for this end point

    Secondary: Number of ADA-positive Participants With Decreased Serum Concentration of Anifrolumab

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    End point title
    Number of ADA-positive Participants With Decreased Serum Concentration of Anifrolumab
    End point description
    Number of participants with decreased serum concentration of anifrolumab due to the ADA-positive results are reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study. Only participants who had ADA-positive assessments with reportable ADA titer results were analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-dose on Day 1) up to Week 168
    End point values
    Anifrolumab
    Number of subjects analysed
    5
    Units: Participants
    1
    No statistical analyses for this end point

    Secondary: Number of ADA-positive Participants With Decreased Pharmacodynamics Response of Anifrolumab

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    End point title
    Number of ADA-positive Participants With Decreased Pharmacodynamics Response of Anifrolumab
    End point description
    Number of participants with decreased pharmacodynamic response of anifrolumab due to ADA-positive results are reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study. Only participants who had ADA-positive assessments with reportable ADA titer results were analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-dose on Day 1) up to Week 168
    End point values
    Anifrolumab
    Number of subjects analysed
    5
    Units: Participants
    1
    No statistical analyses for this end point

    Secondary: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Global Score for ADA Positive Participants

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    End point title
    Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Global Score for ADA Positive Participants
    End point description
    The SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study. Only participants who had ADA-positive assessments with reportable ADA titer results were analysed for this end point. Here 'n' denotes number of participants analysed for specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-dose on Day 1); and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 160, and 168
    End point values
    Anifrolumab
    Number of subjects analysed
    5
    Units: Units on Score
    arithmetic mean (standard deviation)
        Baseline (n= 5)
    7.8 ± 7.6
        Week 12 (n= 4)
    5 ± 2.0
        Week 24 (n= 4)
    1.5 ± 1.9
        Week 36 (n= 4)
    2.0 ± 2.3
        Week 48 (n= 5)
    1.8 ± 2.0
        Week 60 (n= 4)
    2.0 ± 1.6
        Week 72 (n= 2)
    4.0 ± 5.7
        Week 84 (n= 2)
    3.0 ± 1.4
        Week 96 (n= 2)
    3.0 ± 1.4
        Week 108 (n= 2)
    4.0 ± 0.0
        Week 120 (n= 2)
    5.0 ± 1.4
        Week 132 (n= 2)
    4.0 ± 0.0
        Week 144 (n= 2)
    7.0 ± 7.1
        Week 156 (n= 2)
    6.0 ± 2.8
        Week 160 (n= 2)
    2.0 ± 2.8
        Week 168 (n= 2)
    2.0 ± 2.8
    No statistical analyses for this end point

    Secondary: Number of ADA-positive Participants With TEAEs and TESAEs

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    End point title
    Number of ADA-positive Participants With TEAEs and TESAEs
    End point description
    The number of ADA-positive participants with TEAEs and TESAEs are reported. As-treated population was analysed for this endpoint, which included all participants who received any dose of study drug in the OLE study. Only participants who had ADA-positive assessments with reportable ADA titer results were analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-dose on Day 1) up to Week 168
    End point values
    Anifrolumab
    Number of subjects analysed
    5
    Units: Participants
        TEAEs
    5
        TESAEs
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug (Day 1) through 168 weeks
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Anifrolumab Total
    Reporting group description
    Participants received intravenous (IV) infusion of anifrolumab (MEDI-546) 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter received 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.

    Serious adverse events
    Anifrolumab Total
    Total subjects affected by serious adverse events
         subjects affected / exposed
    50 / 218 (22.94%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    1
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Thrombophlebitis superficial
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hodgkin's disease
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    High risk pregnancy
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cyst
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Cervical polyp
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Metrorrhagia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Multiple injuries
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary infarction
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Idiopathic intracranial hypertension
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Oesophageal ulcer
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Hidradenitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Spinal column stenosis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    Hypothalamic pituitary adrenal axis suppression
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Chikungunya virus infection
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Latent tuberculosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Mastoiditis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Otitis media
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences causally related to treatment / all
    2 / 5
         deaths causally related to treatment / all
    1 / 1
    Pneumonia bacterial
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Post procedural infection
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tooth abscess
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Anifrolumab Total
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    164 / 218 (75.23%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Peripheral arterial occlusive disease
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    2
    Peripheral coldness
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    2
    Peripheral venous disease
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Phlebitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Raynaud's phenomenon
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vasculitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Haemangioma of bone
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Melanocytic naevus
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Seborrhoeic keratosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Skin papilloma
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Squamous cell carcinoma of the cervix
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Uterine leiomyoma
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vulvovaginal warts
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    3
    Hypersensitivity
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Seasonal allergy
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    4
    Acquired gene mutation
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Cyst
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Influenza like illness
         subjects affected / exposed
    6 / 218 (2.75%)
         occurrences all number
    10
    Oedema peripheral
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    4
    Pyrexia
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    5
    Tenderness
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Bipolar disorder
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Depressed mood
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Depression
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Insomnia
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    4
    Libido decreased
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Reproductive system and breast disorders
    Breast discharge
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    2
    Breast tenderness
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Cervical dysplasia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Cervical polyp
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Dysmenorrhoea
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Dyspareunia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Endometrial hyperplasia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Endometrial thickening
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Endometriosis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Erectile dysfunction
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Menometrorrhagia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Menorrhagia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Menstruation delayed
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Menstruation irregular
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Ovarian cyst
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pelvic pain
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Polymenorrhoea
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Uterine cervical erosion
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Uterine haemorrhage
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Uterine polyp
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vaginal discharge
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vulvovaginal dryness
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Burns second degree
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Compression fracture
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Contusion
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    5
    Epicondylitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Fall
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Head injury
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Infusion related reaction
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    9
    Injection related reaction
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Joint dislocation
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Ligament sprain
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Limb injury
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    5
    Rib fracture
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Scar
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Skin abrasion
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Blood immunoglobulin a decreased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Blood potassium decreased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Electrocardiogram qt shortened
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Lipids abnormal
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Liver function test increased
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Mycobacterium tuberculosis complex test positive
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Neutrophil count increased
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    4
    Nuclear magnetic resonance imaging brain abnormal
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Transaminases increased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Weight decreased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Weight increased
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Bifascicular block
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Bundle branch block right
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Coronary artery disease
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Left atrial dilatation
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Myocardial fibrosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Palpitations
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Tachycardia
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Asthmatic crisis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Catarrh
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Cough
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    5
    Dysphonia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Emphysema
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Nasal congestion
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pleurisy
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Productive cough
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Reflux laryngitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Rhinitis allergic
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Rhinorrhoea
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Sinus congestion
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Sleep apnoea syndrome
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Snoring
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 218 (2.75%)
         occurrences all number
    6
    Hyperleukocytosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hypercoagulation
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Leukaemoid reaction
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Leukocytosis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    6
    Lymphadenopathy
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Neutropenia
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Neutrophilia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Thrombocytosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    2
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Cerebrovascular disorder
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Dizziness
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    6
    Encephalopathy
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Headache
         subjects affected / exposed
    14 / 218 (6.42%)
         occurrences all number
    21
    Hypersomnia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Intercostal neuralgia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Ischaemic stroke
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Lumbosacral radiculopathy
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Migraine
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    6
    Paraesthesia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pineal gland cyst
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Seizure
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Syncope
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    4
    Visual field defect
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Eye disorders
    Blepharitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Blepharochalasis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Cataract
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    4
    Chalazion
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Eyelid oedema
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Macular degeneration
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Myopia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Scleritis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vision blurred
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Visual acuity reduced
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Eustachian tube dysfunction
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Tympanic membrane perforation
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    3
    Abdominal pain upper
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    6
    Aphthous ulcer
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Chronic gastritis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Constipation
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    5
    Dental caries
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    11 / 218 (5.05%)
         occurrences all number
    12
    Dyspepsia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Enteritis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Gastric mucosa erythema
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Gastric ulcer
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Gastritis
         subjects affected / exposed
    7 / 218 (3.21%)
         occurrences all number
    7
    Gastrointestinal angiodysplasia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Gingival bleeding
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Haemorrhoids
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hiatus hernia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Internal hernia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Mouth ulceration
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    7 / 218 (3.21%)
         occurrences all number
    8
    Noninfective gingivitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pancreatitis chronic
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Toothache
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Vomiting
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hypertonic bladder
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Nephritis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Nephrolithiasis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Ureterolithiasis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Urinary incontinence
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hepatobiliary disorders
    Cholecystitis chronic
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hepatic steatosis
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Hypertransaminasaemia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Actinic keratosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Dermatitis contact
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Drug eruption
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hair growth abnormal
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hypersensitivity vasculitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Idiopathic urticaria
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Keratosis pilaris
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Mechanical urticaria
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Panniculitis
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    4
    Pruritus
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Rash
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    3
    Skin discolouration
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Urticaria
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    4
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    5
    Back pain
         subjects affected / exposed
    7 / 218 (3.21%)
         occurrences all number
    8
    Bursitis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Fibromyalgia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Flank pain
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Foot deformity
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Groin pain
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Joint swelling
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Muscle spasms
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Musculoskeletal chest pain
         subjects affected / exposed
    7 / 218 (3.21%)
         occurrences all number
    7
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Myalgia
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Myofascial pain syndrome
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Myositis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Neck pain
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Osteoarthritis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Osteochondritis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Osteonecrosis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    4
    Osteopenia
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Osteoporosis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Pain in extremity
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Rotator cuff syndrome
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    4
    Scoliosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Spinal pain
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Spondylolisthesis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Temporomandibular joint syndrome
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Tendonitis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    3
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hyperparathyroidism primary
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Thyroid mass
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Acquired mixed hyperlipidaemia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hypercholesterolaemia
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Hyperglycaemia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hyperlipidaemia
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Hypokalaemia
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    6
    Hypomagnesaemia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Hyponatraemia
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Malnutrition
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vitamin d deficiency
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Acarodermatitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Appendicitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Bacterial vaginosis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Body tinea
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Bone abscess
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Bronchitis
         subjects affected / exposed
    28 / 218 (12.84%)
         occurrences all number
    33
    Bronchitis bacterial
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Bronchitis viral
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Candida infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Cellulitis
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    8
    Cervicitis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Conjunctivitis
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Cystitis
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Dermatophytosis of nail
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Ear infection
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Furuncle
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    4
    Gastroenteritis
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    6
    Gastroenteritis viral
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    4
    Gastrointestinal viral infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Genital candidiasis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Genital herpes simplex
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Herpes simplex
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Herpes zoster
         subjects affected / exposed
    10 / 218 (4.59%)
         occurrences all number
    10
    Infected bite
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Influenza
         subjects affected / exposed
    9 / 218 (4.13%)
         occurrences all number
    10
    Latent tuberculosis
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    5
    Lymphangitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Nail infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Nasopharyngitis
         subjects affected / exposed
    32 / 218 (14.68%)
         occurrences all number
    40
    Onychomycosis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Oral candidiasis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    3
    Oral herpes
         subjects affected / exposed
    6 / 218 (2.75%)
         occurrences all number
    7
    Oropharyngeal candidiasis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Otitis media
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    4
    Papilloma viral infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Paronychia
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Parotitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pelvic inflammatory disease
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Peritonsillar abscess
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pharyngitis
         subjects affected / exposed
    10 / 218 (4.59%)
         occurrences all number
    11
    Pharyngitis streptococcal
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Pharyngotonsillitis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Pleurisy viral
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pneumonia
         subjects affected / exposed
    4 / 218 (1.83%)
         occurrences all number
    6
    Pneumonia bacterial
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pulpitis dental
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Pyelonephritis acute
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Rhinitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Sinusitis
         subjects affected / exposed
    8 / 218 (3.67%)
         occurrences all number
    12
    Skin candida
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Skin infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Streptococcal infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Subcutaneous abscess
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    3
    Tinea manuum
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Tonsillitis
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Tracheobronchitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Upper respiratory tract infection
         subjects affected / exposed
    20 / 218 (9.17%)
         occurrences all number
    29
    Urinary tract infection
         subjects affected / exposed
    13 / 218 (5.96%)
         occurrences all number
    17
    Urinary tract infection fungal
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vaginal infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Viral infection
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    5
    Viral upper respiratory tract infection
         subjects affected / exposed
    5 / 218 (2.29%)
         occurrences all number
    6
    Vulval abscess
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    2 / 218 (0.92%)
         occurrences all number
    2
    Vulvovaginal mycotic infection
         subjects affected / exposed
    3 / 218 (1.38%)
         occurrences all number
    3
    Vulvovaginitis
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1
    Zika virus infection
         subjects affected / exposed
    1 / 218 (0.46%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Feb 2013
    Summary of clinical experience was revised to remove the explanation regarding the last day and the first day of the study. Overview of study design was revised to include the explanation that once participants complete treatment and follow-up in the study, signed the informed consent form (ICF), and met all study eligibility criteria, they may be enrolled in this OLE study. Estimated duration of participant's participation and treatment regimen sections in the study were revised to reduce the duration of the study to 2 years. Rationale for study design was updated to remove the reference to participants at least 18 years of age. Inclusion criteria clarified use of adequate contraception for females and males, clarified to state that participants must be willing to forgo other forms of experimental treatment. Withdrawal criteria was clarified for procedures following permanent discontinuation of study drug. Monitoring of dose administration was updated to remove the reference that temperature should be taken orally. Schedule of study procedures for the treatment period and for 85-day follow-up period were revised and updated. Removal of Clinical Evaluation Questionnaire for adverse event of special interest (AESI), addition of procedures for an unscheduled study visit, collection of biomarker samples was made optional, addition of statement that non-serious and serious AESIs should be recorded.
    01 Apr 2013
    Addition of Health-related quality of life impact as exploratory objective and addition of SF-36v2 assessments and analyses to relevant sections, clarification of management of oral corticosteroid (OCS) treatment, addition of hepatitis B virus DNA polymerase chain reaction, QuantiFERON-TB Gold In-tube systemic lupus erythematosus test, immunology profile, urinalysis, urine β human chorionic gonadotropin, and investigator flare question(s) to visit 27, clarification regarding recording of serious and non-serious events of hepatic abnormality as well as AESIs (new or reactivated TB infection, herpes zoster infection, malignancy, infusion, hypersensitivity or anaphylactic reactions, and vasculitis).
    26 Mar 2014
    Duration of IV infusion updated to approximately 60 minutes, updated that for OCS medication taken >40 mg/day of prednisone (or equivalent) for greater than 14 days, dosing with study medication must be withheld until OCS medication can be tapered to ≤40 mg/day, changes in instructions of dose preparation and monitoring of dose administration, modification in schedule of study procedures to state that if Day 1 of the study occurred on Day 422 of study 1013, many of the procedures/assessments only needed to be collected once. If >28-day window elapsed after Day 422, the Day 1 procedures needed to be conducted, serum sample collection of proteomics/biomarkers made optional, guidance for participant who have had recent contact or show signs and symptoms of active tuberculosis (TB), discontinuation of participants due to active TB or noncompliance with latent TB treatment, guidance for pregnancy testing requirements updated.
    12 Feb 2015
    Exemption of participants from requirement of study 1013 completion in regions of Ukraine, interim analysis of study 1013 updated after completion and resulted change in: dose from 1000 mg to 300 mg, infusion time from approximately 60 minutes to at least 30 minutes, and infusion volume based on dose reduction, change in duration of study drug administration from 2 to 3 years, total number of participants randomized in study 1013 (n=307) updated, clarification of permitted study medications and dosing regimens for OCS, clarification that vital signs were to be measured until stable and participant judged by investigator ready for discharge, modification of multiple procedures in the schedule of study assessment, clarification of methodology for multiple study assessments, correction of definition of grade 4 adverse event severity, addition of appendix providing guidance for abnormal liver function test management.

    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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