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    Clinical Trial Results:
    A Multinational, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Investigate the Use of Benralizumab as a Treatment Option for Patients with Bullous Pemphigoid (FJORD)

    Summary
    EudraCT number
    		 2020-000287-32
    Trial protocol
    		 BG   DE   FR   IT   GR  
    Global end of trial date
    26 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Oct 2024
    First version publication date
    13 Oct 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    D325AC00002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04612790
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AstraZeneca AB
    Sponsor organisation address
    Forskargatan 18, Södertälje, Sweden, 151 85
    Public contact
    Global Clinical Lead, AstraZeneca AB, +1 877-240-9479, information.center@astrazeneca.com
    Scientific contact
    Global Clinical Lead, AstraZeneca AB, +1 877-240-9479, information.center@astrazeneca.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Oct 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Oct 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To compare the clinical efficacy of benralizumab with placebo in participants with symptomatic bullous pemphigoid (BP).
    Protection of trial subjects
    This study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with International Council for Harmonisation/Good Clinical Practice, applicable regulatory requirements, and the AstraZeneca policy on Bioethics.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Mar 2021
    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
    Australia: 2
    Country: Number of subjects enrolled
    Bulgaria: 7
    Country: Number of subjects enrolled
    China: 13
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 8
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Israel: 4
    Country: Number of subjects enrolled
    Italy: 10
    Country: Number of subjects enrolled
    Japan: 13
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    United States: 5
    Worldwide total number of subjects
    67
    EEA total number of subjects
    30
    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)
    16
    From 65 to 84 years
    49
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted in adult participants with symptomatic BP at 32 sites in 11 countries. Study consisted of screening period, double-blind (DB) period for 36 weeks followed by optional open-label extension (OLE) period (who completed the DB period), in which all participants received benralizumab for at least 1 year.

    Pre-assignment
    Screening details
    		 Study was terminated following a pre-planned futility analysis as efficacy results did not pass pre-defined futility hurdle. AstraZeneca created protocol#5 and SAP#3 to modify sample size and futility stopping guidelines. Updated protocol was not submitted to health authorities as study was terminating. Results align with protocol#5 and SAP#3.

    Period 1
    Period 1 title
    DB period (Up to 36 weeks)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DB period: Benralizumab
    Arm description
    		 Participants received benralizumab with an initial loading dose of 60 milligrams (mg) followed by a maintenance dose of 30 mg every 4 weeks (Q4W) as a subcutaneous (SC) injection for 36 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Benralizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Benralizumab was provided in an accessorized prefilled syringe (APFS). Participants received benralizumab with an initial loading dose of 60 mg followed by a maintenance dose of 30 mg Q4W as a SC injection for 36 weeks.

    Arm title
    		 DB period: Placebo
    Arm description
    		 Participants received volume-matched placebo as a SC injection on the same dosing schedule as benralizumab Q4W for 36 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Matching placebo was provided in an APFS. Participants received volume-matched placebo as a SC injection on the same dosing schedule as benralizumab Q4W for 36 weeks.

    Number of subjects in period 1
    		DB period: Benralizumab DB period: Placebo
    Started
    34
    33
    Completed
    16
    19
    Not completed
    18
    14
         Consent withdrawn by subject
    2
    4
         Physician decision
    4
    3
         Adverse event, non-fatal
    2
    -
         Death
    1
    1
         Study terminated by sponsor
    8
    6
         Unspecified
    1
    -
    Period 2
    Period 2 title
    OLE period (Up to 1 year)
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 OLE period: Benralizumab (DB)/ Benralizumab (OLE)
    Arm description
    		 Participants who received benralizumab in DB period received benralizumab 30 mg Q4W in OLE period for at least 1 year.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Benralizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Benralizumab was provided in an APFS. Participants who received benralizumab in DB period received benralizumab 30 mg Q4W in OLE period for at least 1 year.

    Arm title
    		 OLE period: Placebo (DB) / Benralizumab (OLE)
    Arm description
    		 Participants who received matched placebo in DB period received benralizumab 30 mg Q4W in OLE period for at least 1 year.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Benralizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Benralizumab was provided in an APFS. Participants who received matched placebo in DB period received benralizumab 30 mg Q4W in OLE period for at least 1 year.

    Number of subjects in period 2 [1]
    		OLE period: Benralizumab (DB)/ Benralizumab (OLE) OLE period: Placebo (DB) / Benralizumab (OLE)
    Started
    16
    18
    Did not receive treatment in OLE period
    0
    1
    Completed
    0
    0
    Not completed
    16
    18
         Consent withdrawn by subject
    -
    1
         Study terminated by sponsor
    14
    15
         Investigator decision
    2
    1
         Unspecified
    -
    1
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 1 participant did not enter OLE period and hence did not receive treatment in OLE period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DB period: Benralizumab
    Reporting group description
    		 Participants received benralizumab with an initial loading dose of 60 milligrams (mg) followed by a maintenance dose of 30 mg every 4 weeks (Q4W) as a subcutaneous (SC) injection for 36 weeks.

    Reporting group title
    DB period: Placebo
    Reporting group description
    		 Participants received volume-matched placebo as a SC injection on the same dosing schedule as benralizumab Q4W for 36 weeks.

    Reporting group values
    		 DB period: Benralizumab DB period: Placebo Total
    Number of subjects
    		 34 33 67
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 10 6 16
        From 65-84 years
    		 24 25 49
        Elderly 85 years and over
    		 0 2 2
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 68.0 ( 10.4 ) 72.5 ( 11.4 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 20 22 42
        Male
    		 14 11 25
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0
        Asian
    		 14 13 27
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 2 0 2
        White
    		 16 20 36
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 2 0 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 1 1
        Not Hispanic or Latino
    		 34 32 66
        Unknown or Not Reported
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    DB period: Benralizumab
    Reporting group description
    		 Participants received benralizumab with an initial loading dose of 60 milligrams (mg) followed by a maintenance dose of 30 mg every 4 weeks (Q4W) as a subcutaneous (SC) injection for 36 weeks.

    Reporting group title
    DB period: Placebo
    Reporting group description
    		 Participants received volume-matched placebo as a SC injection on the same dosing schedule as benralizumab Q4W for 36 weeks.
    Reporting group title
    OLE period: Benralizumab (DB)/ Benralizumab (OLE)
    Reporting group description
    		 Participants who received benralizumab in DB period received benralizumab 30 mg Q4W in OLE period for at least 1 year.

    Reporting group title
    OLE period: Placebo (DB) / Benralizumab (OLE)
    Reporting group description
    		 Participants who received matched placebo in DB period received benralizumab 30 mg Q4W in OLE period for at least 1 year.

    Primary: Percentage of Responders at Week 36

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    End point title
    		 Percentage of Responders at Week 36
    End point description
    A responder was defined as a participant who was in complete remission while off OCS for ≥2 months at Week 36. Participants who received restricted medications or withdrew from the study were considered as non-responders from the time such events occurred up to Week 36. Full analysis set (FAS) included all randomized participants who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study. Only those participants with data collected at Week 36 are reported.
    End point type
    Primary
    End point timeframe
    At Week 36
    End point values
    		 DB period: Benralizumab DB period: Placebo
    Number of subjects analysed
    18
    19
    Units: Percentage of participants
        number (confidence interval 95%)
    11.1 (-2.70 to 26.11)
    5.26 (-5.06 to 15.07)
    Statistical analysis title
    		 DB period: Benralizumab vs DB period: Placebo
    Statistical analysis description
    Estimates were from a logistic regression model using the Firth adjustment (adj) that included treatment group, baseline disease severity (moderate, severe) and time of BP diagnosis (participants with newly diagnosed BP, participants with a previous diagnosis of BP who have relapsed) as categorical covariates.
    Comparison groups
    DB period: Benralizumab v DB period: Placebo
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.509
    Method
    		 Logistic regression model with Firth adj
    Parameter type
    		 Difference in percentage of responders
    Point estimate
    6.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.9
         upper limit
    		 24.29

    Secondary: Percentage of Participants who Remained Relapse-Free up to Week 36

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    End point title
    		 Percentage of Participants who Remained Relapse-Free up to Week 36
    End point description
    Relapse was defined as the appearance of 3 or more new lesions per month (blisters, eczematous lesions, or urticarial plaques); or at least 1 large (>10 centimeter [cm] diameter) eczematous lesion or urticarial plaques that did not heal within 1 week; or the extension of established lesions or daily pruritus in participants who had achieved disease control. FAS included all randomized participants who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study. Only those participants with data collected at specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Up to Week 36
    End point values
    		 DB period: Benralizumab DB period: Placebo
    Number of subjects analysed
    18
    19
    Units: Percentage of participants
        number (confidence interval 95%)
    23.78 (5.95 to 41.61)
    19.79 (1.43 to 38.15)
    No statistical analyses for this end point

    Secondary: Cumulative OCS Exposure from Baseline to Week 36

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    End point title
    		 Cumulative OCS Exposure from Baseline to Week 36
    End point description
    The cumulative OCS exposure was estimated as the sum over the relevant 4-week periods from the mixed-effect model for repeated measures (MMRM) model. Baseline was defined as the last recorded value on or prior to the date of randomization. Equivalents were prednisone equivalents (converted from mg). FAS included all randomized participants who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study. Only those participants with data collected at specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 36
    End point values
    		 DB period: Benralizumab DB period: Placebo
    Number of subjects analysed
    18
    19
    Units: mg per kilogram (mg/kg)
        arithmetic mean (standard deviation)
    71.37 ( 63.19 )
    62.71 ( 46.90 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Bullous Pemphigoid Disease Area Index (BPDAI) Activity Score at Week 36

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    End point title
    		 Change From Baseline in Bullous Pemphigoid Disease Area Index (BPDAI) Activity Score at Week 36
    End point description
    BPDAI is a clinician completed tool that is used for independent disease severity assessment to measure disease extent in BP. The total BPDAI activity score is calculated as the arithmetic sum of the 3 subcomponents – cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. The BPDAI total activity gives an indication of disease activity, with score range from 0 (no disease activity) to 360 (severe disease activity). Higher scores indicating greater disease activity. Baseline was defined as the last recorded value on or prior to the date of randomization. FAS included all randomized participants who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study. Only those participants with data collected at specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 36
    End point values
    		 DB period: Benralizumab DB period: Placebo
    Number of subjects analysed
    14
    12
    Units: Score on a scale
        arithmetic mean (standard deviation)
    -53.29 ( 46.33 )
    -52.75 ( 17.36 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in BPDAI-Pruritus Score at Week 36

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    End point title
    		 Change From Baseline in BPDAI-Pruritus Score at Week 36
    End point description
    The BPDAI-Pruritus is a separate component of the BPDAI that asks the participant to grade the severity of pruritus over the past 24 hours, the past week, and the past month. For each recall period, severity of pruritus is rated on a numeric rating scale (NRS) ranging from 0 for no itch to 10 for maximal itching. The BPDAI-Pruritus score was computed as the sum of 3 components ranging from 0 to 30. Higher scores indicated worse condition. Baseline was defined as the last recorded value on or prior to the date of randomization. FAS included all randomized participants who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study. Only those participants with data collected at specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 36
    End point values
    		 DB period: Benralizumab DB period: Placebo
    Number of subjects analysed
    14
    12
    Units: Score on a scale
        arithmetic mean (standard deviation)
    -5.57 ( 7.23 )
    -16.58 ( 9.21 )
    No statistical analyses for this end point

    Secondary: Cumulative OCS Exposure From Baseline to Week 16

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    End point title
    		 Cumulative OCS Exposure From Baseline to Week 16
    End point description
    The cumulative OCS exposure was estimated as the sum over the relevant 4-week periods from the MMRM model. Baseline was defined as the last recorded value on or prior to the date of randomization. Equivalents were prednisone equivalents (converted from mg). FAS included all randomized participants who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study. Only those participants with data collected at specified timepoints are reported.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 16
    End point values
    		 DB period: Benralizumab DB period: Placebo
    Number of subjects analysed
    24
    24
    Units: mg/kg
        arithmetic mean (standard deviation)
    46.90 ( 27.19 )
    42.15 ( 33.33 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent Adverse events(TEAEs) and all-cause mortality: Start of study treatment(Day 1) up to the follow up visit(4 weeks after the last dose of study treatment), or up until the study withdrawal date if earlier,up to approximately 133 weeks.
    Adverse event reporting additional description
    The safety analysis set consists of all participants who had received at least 1 dose of IP.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    DB period: Benralizumab
    Reporting group description
    		 Participants received benralizumab with an initial loading dose of 60 mg followed by a maintenance dose of 30 mg Q4W by SC injection for 36 weeks.

    Reporting group title
    OLE period: Benralizumab (DB)/Benralizumab (OLE)
    Reporting group description
    		 Participants who received benralizumab in DB period received benralizumab 30 mg Q4W in OLE period for at least 1 year.

    Reporting group title
    OLE period: Placebo (DB)/Benralizumab (OLE)
    Reporting group description
    		 Participants who received matched placebo in DB period benralizumab 30 mg Q4W in OLE period for at least 1 year.

    Reporting group title
    DB period: Placebo
    Reporting group description
    		 Participants received matched placebo by SC injection Q4W for 36 weeks.

    Serious adverse events
    		 DB period: Benralizumab OLE period: Benralizumab (DB)/Benralizumab (OLE) OLE period: Placebo (DB)/Benralizumab (OLE) DB period: Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 34 (26.47%)
    4 / 16 (25.00%)
    2 / 18 (11.11%)
    8 / 33 (24.24%)
         number of deaths (all causes)
    1
    0
    0
    1
         number of deaths resulting from adverse events
    1
    0
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound dehiscence
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure acute
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary oedema
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pemphigoid
         subjects affected / exposed
    4 / 34 (11.76%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Henoch-schonlein purpura
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 16 (12.50%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Covid-19 pneumonia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Covid-19
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 16 (12.50%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DB period: Benralizumab OLE period: Benralizumab (DB)/Benralizumab (OLE) OLE period: Placebo (DB)/Benralizumab (OLE) DB period: Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    22 / 34 (64.71%)
    8 / 16 (50.00%)
    8 / 18 (44.44%)
    23 / 33 (69.70%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 34 (8.82%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    2 / 33 (6.06%)
         occurrences all number
    5
    1
    1
    2
    Flushing
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    2 / 33 (6.06%)
         occurrences all number
    1
    0
    1
    3
    Oedema peripheral
         subjects affected / exposed
    4 / 34 (11.76%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    5
    0
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    1
    0
    0
    2
    Dyspnoea
         subjects affected / exposed
    1 / 34 (2.94%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences all number
    0
    1
    0
    1
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Weight increased
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    1 / 33 (3.03%)
         occurrences all number
    2
    0
    0
    1
    Lymphocyte count decreased
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    2
    Heart rate increased
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Injury, poisoning and procedural complications
    Fracture
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Contusion
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    3 / 33 (9.09%)
         occurrences all number
    0
    0
    0
    4
    Arthropod bite
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Ventricular hypokinesia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    2
    Eye disorders
    Ocular hypertension
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Cataract
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    1 / 33 (3.03%)
         occurrences all number
    1
    0
    1
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    1
    0
    0
    2
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Haemorrhoids
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Hiatus hernia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Nausea
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    1 / 33 (3.03%)
         occurrences all number
    0
    0
    1
    1
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Skin ulcer
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    2
    Dermatitis contact
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Eczema
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    1 / 33 (3.03%)
         occurrences all number
    0
    4
    1
    1
    Lichenoid keratosis
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Miliaria
         subjects affected / exposed
    1 / 34 (2.94%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Urticaria
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    1 / 33 (3.03%)
         occurrences all number
    2
    0
    1
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    3
    Renal impairment
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    2
    Haematuria
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 16 (12.50%)
    2 / 18 (11.11%)
    2 / 33 (6.06%)
         occurrences all number
    0
    2
    2
    2
    Osteoarthritis
         subjects affected / exposed
    0 / 34 (0.00%)
    2 / 16 (12.50%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Back pain
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    2
    0
    0
    2
    Infections and infestations
    Oral candidiasis
         subjects affected / exposed
    2 / 34 (5.88%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    1 / 33 (3.03%)
         occurrences all number
    2
    0
    1
    1
    Onychomycosis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 34 (5.88%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    3
    1
    2
    0
    Herpes zoster
         subjects affected / exposed
    4 / 34 (11.76%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    4
    0
    0
    2
    Coronavirus infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Bronchitis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    1 / 33 (3.03%)
         occurrences all number
    0
    0
    1
    1
    Body tinea
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Covid-19
         subjects affected / exposed
    6 / 34 (17.65%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    4 / 33 (12.12%)
         occurrences all number
    6
    0
    1
    4
    Urinary tract infection
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    1 / 18 (5.56%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    1
    2
    Tinea pedis
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    2
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Obesity
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Hypoglycaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    0 / 16 (0.00%)
    0 / 18 (0.00%)
    2 / 33 (6.06%)
         occurrences all number
    0
    0
    0
    2
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    0 / 18 (0.00%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    0
    0
    Dehydration
         subjects affected / exposed
    0 / 34 (0.00%)
    1 / 16 (6.25%)
    1 / 18 (5.56%)
    0 / 33 (0.00%)
         occurrences all number
    0
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Nov 2020
    The primary reason for this amendment was to take regulatory feedback into account. Primary endpoint text changed to ‘a responder is defined as a participant who is in complete remission while off OCS for ≥ 2 months at Week 36’ instead of ‘a responder is defined as a participant who is in partial or complete remission off OCS for ≥ 2 months at Week 36’.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated following a pre-planned futility analysis as the efficacy results did not pass the pre-defined futility hurdle with no new safety concerns.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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