Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39818   clinical trials with a EudraCT protocol, of which   6535   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2a, Randomized, Placebo-controlled, Proof of Mechanism Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Subjects with Primary Sjogren’s Syndrome

    Summary
    EudraCT number
    2014-003896-41
    Trial protocol
    GB   SE  
    Global end of trial date
    13 Aug 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    23 Aug 2019
    First version publication date
    23 Aug 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    D5181C00001
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02334306
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    One MedImmune Way, Maryland, Gaithersburg, United States, 20878
    Public contact
    Gabor Illei, MedImmune, LLC, +1 240 558 0038 118, information.center@astrazenea.com
    Scientific contact
    Gabor Illei, MedImmune, LLC, +1 240 558 0038 118, information.center@astrazenea.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
    13 Sep 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Aug 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate the effect of AMG 557/MEDI5872 compared to placebo in reducing objective measures of overall disease activity in subjects with primary Sjogren’s syndrome.
    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. Subjects 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
    08 Jun 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Sweden: 4
    Country: Number of subjects enrolled
    United Kingdom: 11
    Country: Number of subjects enrolled
    United States: 6
    Worldwide total number of subjects
    32
    EEA total number of subjects
    26
    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)
    27
    From 65 to 84 years
    5
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This study was conducted across 4 countries (France, United Kingdom, Sweden, and the United States).

    Pre-assignment
    Screening details
    A total of 59 participants were screened in the study. Of which, 27 participants were screen failures and 32 participants were randomized and enrolled in study.

    Period 1
    Period 1 title
    Double-blind period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Participants received a subcutaneous (SC) dose of placebo matching with MEDI5872 every week (QW) for 3 weeks (Days 1, 8, and 15) and then every 2 weeks (Q2W) for next 9 weeks (Days 29 to 85) in double-blind period of the study.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo matching to MEDI5872 was administered subcutaneously QW for 3 weeks (Days 1, 8, and 15) and then Q2W for next 9 weeks (Days 29 to 85).

    Arm title
    MEDI5872 210 mg
    Arm description
    Participants received a fixed SC dose of 210 mg MEDI5872 QW for 3 weeks (Days 1, 8, and 15) and then Q2W for next 9 weeks (Days 29 to 85) in double-blind period of the study.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI5872
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    MEDI5872 210 mg was administered subcutaneously QW for 3 weeks (Days 1, 8, and 15) and then Q2W for next 9 weeks (Days 29 to 85).

    Number of subjects in period 1
    Placebo MEDI5872 210 mg
    Started
    16
    16
    Completed
    15
    14
    Not completed
    1
    2
         Adverse event, non-fatal
    -
    1
         Consent withdrawn by subject
    1
    1
    Period 2
    Period 2 title
    Open-label period
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo/MEDI5872 210 mg
    Arm description
    Participants who received placebo in double-blind period, received MEDI5872 QW from Days 99 to 113 and Q2W from Days 127 to 183 in open-label period of the study.
    Arm type
    Experimental

    Investigational medicinal product name
    MEDI5872
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants who received placebo in double-blind period, received MEDI5872 QW from Days 99 to 113 and Q2W from Days 127 to 183.

    Arm title
    MEDI5872 210 mg/MEDI5872 210 mg
    Arm description
    Participants who received MEDI5872 210 mg in double-blind period, continued to receive MEDI5872 210 mg Q2W from Days 99 to 183 and received an additional dose of blinded placebo on Day 106 in open-label period of the study.
    Arm type
    Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo was administered subcutaneously on Day 106 for participants who received MEDI5872 in double-blind period.

    Investigational medicinal product name
    MEDI5872
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants who received MEDI5872 in double-blind period were continued to receive MEDI5872 210mg Q2W from Days 99 to 183.

    Number of subjects in period 2
    Placebo/MEDI5872 210 mg MEDI5872 210 mg/MEDI5872 210 mg
    Started
    15
    14
    Completed
    15
    14

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received a subcutaneous (SC) dose of placebo matching with MEDI5872 every week (QW) for 3 weeks (Days 1, 8, and 15) and then every 2 weeks (Q2W) for next 9 weeks (Days 29 to 85) in double-blind period of the study.

    Reporting group title
    MEDI5872 210 mg
    Reporting group description
    Participants received a fixed SC dose of 210 mg MEDI5872 QW for 3 weeks (Days 1, 8, and 15) and then Q2W for next 9 weeks (Days 29 to 85) in double-blind period of the study.

    Reporting group values
    Placebo MEDI5872 210 mg Total
    Number of subjects
    16 16 32
    Age categorical
    The subject analysis set for baseline characteristics was "Intent-to-treat (ITT) population". ITT population included all randomized and treated participants, grouped according to assigned treatment.
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    0 0 0
        Adolescents (12-17 years)
    0 0 0
        Adults (18-64 years)
    15 12 27
        From 65-84 years
    1 4 5
        85 years and over
    0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    50.2 ± 12 51.1 ± 14.3 -
    Sex: Female, Male
    Units: Subjects
        Female
    14 14 28
        Male
    2 2 4

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received a subcutaneous (SC) dose of placebo matching with MEDI5872 every week (QW) for 3 weeks (Days 1, 8, and 15) and then every 2 weeks (Q2W) for next 9 weeks (Days 29 to 85) in double-blind period of the study.

    Reporting group title
    MEDI5872 210 mg
    Reporting group description
    Participants received a fixed SC dose of 210 mg MEDI5872 QW for 3 weeks (Days 1, 8, and 15) and then Q2W for next 9 weeks (Days 29 to 85) in double-blind period of the study.
    Reporting group title
    Placebo/MEDI5872 210 mg
    Reporting group description
    Participants who received placebo in double-blind period, received MEDI5872 QW from Days 99 to 113 and Q2W from Days 127 to 183 in open-label period of the study.

    Reporting group title
    MEDI5872 210 mg/MEDI5872 210 mg
    Reporting group description
    Participants who received MEDI5872 210 mg in double-blind period, continued to receive MEDI5872 210 mg Q2W from Days 99 to 183 and received an additional dose of blinded placebo on Day 106 in open-label period of the study.

    Subject analysis set title
    Any MEDI5872 210 mg
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Participants received at least one dose of MEDI5872 treatment either during double-blind and/or open-label period of the study. One participant from ‘Placebo’ arm discontinued treatment before Day 99, didn’t receive MEDI5872 dose and entered in safety follow-up period.

    Primary: Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99

    Close Top of page
    End point title
    Change From Baseline in European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) Score at Day 99
    End point description
    In ESSDAI, physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological), with each domain activity level as 3 or 4 levels (no, low, moderate, high) according to their severity (0 = no disease activity; 3 or 4 = high disease activity). Each domain is assigned a weight between 1 and 6, and domain score is multiplied by domain weight. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 [best] to 123 [worst activity]). A higher score indicates worsening of the disease. Adjusted mean change and standard error are presented. Intent-to-treat (ITT) population was analysed for this end point, which included all randomized and treated participants, grouped according to assigned treatment. Number to Subjects Analyzed = number of participants evaluated for this end point.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1 predose) and Day 99
    End point values
    Placebo MEDI5872 210 mg
    Number of subjects analysed
    16
    13
    Units: Scores on a scale
        arithmetic mean (standard error)
    -2.3 ± 0.8
    -3.8 ± 0.9
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.262
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    -1.4
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.6
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.3

    Secondary: Ratio to Baseline in Peripheral Blood Biomarkers at Day 99

    Close Top of page
    End point title
    Ratio to Baseline in Peripheral Blood Biomarkers at Day 99
    End point description
    The peripheral blood biomarkers included total plasma cell levels (including plasma blast levels) and T follicular helper (TFH) cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented. The ITT population was analysed for this end point, which included all randomized and treated participants, grouped according to assigned treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 predose) and Day 99
    End point values
    Placebo MEDI5872 210 mg
    Number of subjects analysed
    16
    16
    Units: Ratio
    geometric mean (standard error)
        Plasma Cell Levels
    0.70 ± 0.24
    0.65 ± 0.24
        TFH Cells
    0.94 ± 0.27
    0.62 ± 0.27
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Statistical analysis description
    For plasma cell levels
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.82
    Method
    ANCOVA
    Parameter type
    Geometric mean ratio
    Point estimate
    0.93
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.52
         upper limit
    1.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.33
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Statistical analysis description
    For TFH cells
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.291
    Method
    ANCOVA
    Parameter type
    Geometric mean ratio
    Point estimate
    0.65
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.33
         upper limit
    1.28
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.4

    Secondary: Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99

    Close Top of page
    End point title
    Ratio to Baseline in Minor Salivary Gland Tissue Biomarkers at Day 99
    End point description
    The minor salivary gland biopsy biomarkers included total plasma cell levels, CD4/ inducible T-cell costimulator (ICOS) TFH cells, and PD-1/ICOS TFH cells. Adjusted geometric mean ratio to baseline and standard error (log) are presented. The ITT population was analysed for this end point, which included all randomized and treated participants, grouped according to assigned treatment. The “Number of Subjects Analyzed” denotes the number of participants evaluated for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 predose) and Day 99
    End point values
    Placebo MEDI5872 210 mg
    Number of subjects analysed
    9
    11
    Units: Ratio
    geometric mean (standard error)
        Total Plasma Cells
    1.32 ± 0.13
    1.15 ± 0.11
        CD4/ICOS TFH Cells
    1.76 ± 0.21
    0.75 ± 0.18
        PD-1/ICOS TFH Cells
    1.06 ± 0.19
    1.07 ± 0.16
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Statistical analysis description
    For total plasma cells
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.44
    Method
    ANCOVA
    Parameter type
    Geometric mean ratio
    Point estimate
    0.87
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.65
         upper limit
    1.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.17
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Statistical analysis description
    For CD4/ICOS TFH cells
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.008
    Method
    ANCOVA
    Parameter type
    Geometric mean ratio
    Point estimate
    0.43
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.26
         upper limit
    0.7
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.28
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Statistical analysis description
    For PD-1/ICOS TFH cells
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.972
    Method
    ANCOVA
    Parameter type
    Geometric mean ratio
    Point estimate
    1.01
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    0.64
         upper limit
    1.59
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.26

    Secondary: Ratio to Baseline in Focus Score at Day 99

    Close Top of page
    End point title
    Ratio to Baseline in Focus Score at Day 99
    End point description
    The focus score is a semi-quantitative assessment of focal lymphocytic sialoadenitis, which is defined as the presence of >= 1 dense aggregate of 50 or more lymphocytes in a 4 mm^2 area. Higher numbers are associated with more inflammation. The ITT population was analysed for this end point, which included all randomized and treated participants, grouped according to assigned treatment. The “Number of Subjects Analyzed” denotes the number of participants evaluated for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 predose) and Day 99
    End point values
    Placebo MEDI5872 210 mg
    Number of subjects analysed
    6
    10
    Units: Ratio
        arithmetic mean (standard deviation)
    0.79 ± 0.53
    0.96 ± 0.50
    No statistical analyses for this end point

    Secondary: Change From Baseline in European League Against Rheumatism Sjogren’s Syndrome Patient Reported Index (ESSPRI) Score at Day 99

    Close Top of page
    End point title
    Change From Baseline in European League Against Rheumatism Sjogren’s Syndrome Patient Reported Index (ESSPRI) Score at Day 99
    End point description
    The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren’s syndrome. It consists of three questions covering the cardinal symptoms of Sjögren’s syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Adjusted mean change and standard error are presented. The ITT population was analysed for this end point, which included all randomized and treated participants, grouped according to assigned treatment.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 predose) and Day 99
    End point values
    Placebo MEDI5872 210 mg
    Number of subjects analysed
    16
    16
    Units: Scores on a scale
        arithmetic mean (standard error)
    -1.0 ± 0.5
    -0.6 ± 0.5
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.574
    Method
    ANCOVA
    Parameter type
    Mean difference (net)
    Point estimate
    0.4
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.8
         upper limit
    1.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.7

    Secondary: Percentage of ESSDAI Responders at Day 99

    Close Top of page
    End point title
    Percentage of ESSDAI Responders at Day 99
    End point description
    In ESSDAI, physician scores the disease activity level of 12 organ-specific domains (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, and biological), with each domain activity level as 3 or 4 levels (no, low, moderate, high) according to their severity (0 = no disease activity; 3 or 4 = high disease activity). Each domain is assigned a weight between 1 and 6, and domain score is multiplied by domain weight. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 [best] to 123 [worst activity]). Participants are considered to be an ESSDAI[x] responder as they achieved a reduction of x points or more in ESSDAI score, did not prematurely discontinue the study drug, and did not receive prohibited concomitant medications. The ITT population was analysed for this end point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1 predose) and Day 99
    End point values
    Placebo MEDI5872 210 mg
    Number of subjects analysed
    16
    16
    Units: Percentage of participants
    number (not applicable)
        ESSDAI [3]|
    18.8
    43.8
        ESSDAI [4]|
    18.8
    43.8
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Statistical analysis description
    ESSDAI[4]
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.252
    Method
    Fisher exact
    Parameter type
    Difference in precentages
    Point estimate
    25
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.1
         upper limit
    50.9
    Statistical analysis title
    Placebo and MEDI5872 210 mg
    Statistical analysis description
    ESSDAI [3]
    Comparison groups
    Placebo v MEDI5872 210 mg
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.252
    Method
    Fisher exact
    Parameter type
    Difference in percentages
    Point estimate
    25
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -3.1
         upper limit
    50.9

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

    Close Top of page
    End point title
    Number of Participants 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. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. 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. Placebo: As-treated population (participants grouped per actual treatment received). Any MEDI5872 210 mg: Any MEDI5872 population (participants received at least 1 dose of MEDI5872 either in double-blind and/or open-label). 1 participant from ‘Placebo’ discontinued treatment before Day 99 and didn’t receive MEDI5872 dose in open-label period.
    End point type
    Secondary
    End point timeframe
    Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Placebo Any MEDI5872 210 mg
    Number of subjects analysed
    16
    31
    Units: Participants
        Any TEAEs|
    14
    29
        Any TESAEs|
    0
    1
    No statistical analyses for this end point

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

    Close Top of page
    End point title
    Number of Participants With Adverse Events of Special Interest (AESIs) [2]
    End point description
    An AESI (serious or non-serious) was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, new or reactivated tuberculosis infection, malignancy, and hypersensitivity and anaphylactic reactions. Placebo: As-treated population (participants grouped per actual treatment received). Any MEDI5872 210 mg: Any MEDI5872 population (participants received at least 1 dose of MEDI5872 either in double-blind and/or open-label). 1 participant from ‘Placebo’ discontinued treatment before Day 99 and didn’t receive MEDI5872 dose in open-label period.
    End point type
    Secondary
    End point timeframe
    Placebo arm: Day 1 (postdose) through Day 99 (predose); Any MEDI5872 210 mg arm: Day 1 (postdose) through Day 296 for MEDI5872 210 mg arm, and Day 99 (postdose) through Day 296 for participants who received placebo at double-blind period
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Only those baseline period arms for which analysis was planned were reported in the end point.
    End point values
    Placebo Any MEDI5872 210 mg
    Number of subjects analysed
    16
    31
    Units: Participants
    1
    6
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Placebo: Days 1 to 99; Any MEDI5872 210 mg: Days 1 to 296 for MEDI5872 210 mg arm, and Days 99 to 296 for participants who received placebo at double-blind. One participant from ‘Placebo’ discontinued before Day 99 and entered directly in safety period.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Any MEDI5872 210 mg
    Reporting group description
    Participants received at least one dose of MEDI5872 treatment either during double-blind and/or open-label period of the study. In double-bind period, participants received a fixed SC dose of 210 mg MEDI5872 QW for 3 weeks (Days 1, 8, and 15) and then every Q2W for 9 weeks (Days 29 to 85). In open-label period, participants who received MEDI5872 210mg in double-blinded period received MEDI5872 210mg on Days 99 and Day 113; and participants who received placebo in double-blinded period received MEDI5872 210mg QW from Days 99 to 113, later all participants received MEDI5872 210mg Q2W from Days 127 to 183 and were followed up till Day 296.

    Reporting group title
    Placebo
    Reporting group description
    Participants received a subcutaneous (SC) dose of placebo matching with MEDI5872 every week (QW) for 3 weeks (Days 1, 8, and 15) and then every 2 weeks (Q2W) for next 9 weeks (Days 29 to 85) in double-blind period of the study.

    Serious adverse events
    Any MEDI5872 210 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Gastrointestinal disorders
    Small intestine polyp
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Any MEDI5872 210 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 31 (93.55%)
    14 / 16 (87.50%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    4
    0
    Hot flush
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Hypotension
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Facial pain
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0
    Fatigue
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Feeling hot
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Influenza like illness
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Injection site bruising
         subjects affected / exposed
    0 / 31 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    0
    2
    Injection site erythema
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    7
    0
    Injection site haematoma
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Injection site pain
         subjects affected / exposed
    3 / 31 (9.68%)
    0 / 16 (0.00%)
         occurrences all number
    5
    0
    Injection site rash
         subjects affected / exposed
    4 / 31 (12.90%)
    0 / 16 (0.00%)
         occurrences all number
    5
    0
    Injection site reaction
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Local swelling
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Vaccination site reaction
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Depression
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Stress
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Metrorrhagia
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Vaginal haemorrhage
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Injury, poisoning and procedural complications
    Epicondylitis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Accidental device ingestion
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Face injury
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Fall
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Ligament rupture
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Post procedural swelling
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Procedural complication
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Procedural pain
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Skin abrasion
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Soft tissue injury
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Thermal burn
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0
    Tooth avulsion
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood urine present
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    4
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 31 (3.23%)
    2 / 16 (12.50%)
         occurrences all number
    1
    2
    Nasal congestion
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Productive cough
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 31 (6.45%)
    1 / 16 (6.25%)
         occurrences all number
    2
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Lymphopenia
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0
    Dysgeusia
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    5 / 31 (16.13%)
    2 / 16 (12.50%)
         occurrences all number
    8
    2
    Sciatica
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    2
    Syncope
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 31 (9.68%)
    0 / 16 (0.00%)
         occurrences all number
    4
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    4 / 31 (12.90%)
    0 / 16 (0.00%)
         occurrences all number
    5
    0
    Dental caries
         subjects affected / exposed
    3 / 31 (9.68%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0
    Diarrhoea
         subjects affected / exposed
    4 / 31 (12.90%)
    2 / 16 (12.50%)
         occurrences all number
    4
    2
    Diarrhoea haemorrhagic
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Dry mouth
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Dysphagia
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Food poisoning
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Irritable bowel syndrome
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Lip blister
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Nausea
         subjects affected / exposed
    2 / 31 (6.45%)
    3 / 16 (18.75%)
         occurrences all number
    2
    3
    Paraesthesia oral
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Parotid gland enlargement
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    2
    Reflux gastritis
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Tongue blistering
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Tooth loss
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Micturition urgency
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Hepatic steatosis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Erythema
         subjects affected / exposed
    3 / 31 (9.68%)
    1 / 16 (6.25%)
         occurrences all number
    4
    2
    Eczema
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    3
    Night sweats
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Papule
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Pruritus
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Rash
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    7
    0
    Purpura
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Rash papular
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Rash pruritic
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Swelling face
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    4 / 31 (12.90%)
    0 / 16 (0.00%)
         occurrences all number
    5
    0
    Back pain
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Bone pain
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Dupuytren's contracture
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Bursitis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Joint effusion
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Flank pain
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Joint swelling
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Limb mass
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
         subjects affected / exposed
    0 / 31 (0.00%)
    2 / 16 (12.50%)
         occurrences all number
    0
    2
    Myalgia
         subjects affected / exposed
    1 / 31 (3.23%)
    2 / 16 (12.50%)
         occurrences all number
    1
    2
    Neck pain
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Sjogren's syndrome
         subjects affected / exposed
    3 / 31 (9.68%)
    0 / 16 (0.00%)
         occurrences all number
    3
    0
    Tendonitis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Spinal pain
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Calcium deficiency
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Decreased appetite
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Iron deficiency
         subjects affected / exposed
    1 / 31 (3.23%)
    1 / 16 (6.25%)
         occurrences all number
    1
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Bronchopulmonary aspergillosis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Conjunctivitis
         subjects affected / exposed
    2 / 31 (6.45%)
    2 / 16 (12.50%)
         occurrences all number
    2
    2
    Gastroenteritis viral
         subjects affected / exposed
    2 / 31 (6.45%)
    1 / 16 (6.25%)
         occurrences all number
    2
    1
    Genital candidiasis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Lower respiratory tract infection
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 31 (0.00%)
    1 / 16 (6.25%)
         occurrences all number
    0
    1
    Oral herpes
         subjects affected / exposed
    3 / 31 (9.68%)
    0 / 16 (0.00%)
         occurrences all number
    7
    0
    Paronychia
         subjects affected / exposed
    2 / 31 (6.45%)
    0 / 16 (0.00%)
         occurrences all number
    2
    0
    Parotitis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Pharyngitis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Serratia infection
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Tongue fungal infection
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Tooth abscess
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 31 (12.90%)
    1 / 16 (6.25%)
         occurrences all number
    6
    1
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 31 (25.81%)
    4 / 16 (25.00%)
         occurrences all number
    8
    5
    Viral pharyngitis
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    2 / 31 (6.45%)
    2 / 16 (12.50%)
         occurrences all number
    2
    3
    Vulvovaginal mycotic infection
         subjects affected / exposed
    1 / 31 (3.23%)
    0 / 16 (0.00%)
         occurrences all number
    1
    0

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Nov 2014
    • Added criteria for discontinuation of investigational product and for study suspension/termination, to specify the number and type of adverse events that would trigger either action. • Added a primary analysis of the primary endpoint at Study Day 99 that would not change at the final analysis, and indicated that the Sponsor would be unblinded at the primary analysis (after Study Day 99) but other study/site staff and subjects would remain blinded until the study was complete. • Added methotrexate >20 mg/week as a prohibited concomitant medication.
    28 Aug 2015
    • Modified Exclusion Criteria to exclude subjects with only systemic fungal infections and allow subjects with topical fungal infections
    17 Feb 2016
    • Modified Inclusion Criteria to raise the upper age limit from 70 to 75 years. • Modified Inclusion Criteria to lower the IgG requirement from 16g/dL to 13 g/dL, and to include a positive test for cryoglobulins. • Modified Exclusion Criteria to lower the white blood cell count from < 2000 × 10^6/L to < 1500 × 10^6/L and to lower the neutrophil count requirement from < 1500 × 10^6/L to < 1000 × 10^6/L.
    24 Oct 2017
    • Moved the exploratory endpoint of ESSDAI response to become a secondary endpoint as an objective measure of overall disease activity supporting secondary objective. • Added ESSPRI response and MDGA as a new Exploratory Endpoints.

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA