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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Clinical Trial in Subjects with Active Psoriatic Arthritis to Investigate Efficacy, Tolerability, Safety, Pharmacokinetics and Immunogenicity of Izokibep (ABY-035)

    Summary
    EudraCT number
    		 2019-003405-94
    Trial protocol
    		 AT   HU   CZ   DE   ES   BE  
    Global end of trial date
    20 Apr 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    13 Dec 2024
    First version publication date
    09 Aug 2023
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Added pharmacokinetic (PK) endpoint.

    Trial information

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    Trial identification
    Sponsor protocol code
    ABY-035-202
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04713072
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    ACELYRIN, INC.
    Sponsor organisation address
    4149 Liberty Canyon Rd, Agoura Hills, United States, CA 91301
    Public contact
    Clinical Trial Information Desk, ACELYRIN, INC., +1 805-456-4393, clinicaltrials@acelyrin.com
    Scientific contact
    Clinical Trial Information Desk, ACELYRIN, INC., +1 805-456-4393, clinicaltrials@acelyrin.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
    20 Apr 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Apr 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to evaluate efficacy of different dose regimens of ABY-035 compared with placebo in subjects with active psoriatic arthritis (PsA).
    Protection of trial subjects
    This study was conducted in accordance with International Council on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Aug 2020
    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
    Austria: 1
    Country: Number of subjects enrolled
    Czechia: 33
    Country: Number of subjects enrolled
    Spain: 15
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Poland: 46
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Hungary: 21
    Worldwide total number of subjects
    135
    EEA total number of subjects
    135
    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)
    122
    From 65 to 84 years
    13
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This study was conducted at 28 trial centres in 7 European countries (Austria, Belgium, Czech Republic, Germany, Hungary, Poland, Spain) from 04 August 2020 to 20 April 2022.

    Pre-assignment
    Screening details
    		 One-hundred ninety-seven subjects with confirmed PsA were screened, of which 135 subjects were found eligible and were randomized in a 1:1:1 ratio to 1 of the 3 treatment arms in period 1. The trial was prematurely terminated during Treatment Period II via Amendment 2 by sponsor decision to accelerate clinical development.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Treatment Period 1: izokibep 40 mg Q2W
    Arm description
    		 Subjects received lower dose izokibep 40 mg subcutaneously (SC) every 2 weeks (Q2W) during treatment period 1 which spanned weeks 0 to 16.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INN: izokibep
    Investigational medicinal product code
    ABY-035
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received izokibep 40 mg SC injection Q2W.

    Arm title
    		 Treatment Period 1: izokibep 80 mg Q2W
    Arm description
    		 Subjects received higher dose izokibep 80 mg SC injection Q2W during treatment period 1 which spanned weeks 0 to 16.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INN: izokibep
    Investigational medicinal product code
    ABY-035
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received izokibep 80 mg SC injection Q2W.

    Arm title
    		 Treatment Period 1: Placebo
    Arm description
    		 Subject received matched placebo SC injection Q2W from Week 0 through Week 14.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Placebo
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received matched placebo solution for SC injection Q2W.

    Number of subjects in period 1
    		Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo
    Started
    44
    47
    44
    Completed
    42
    46
    43
    Not completed
    2
    1
    1
         Adverse event, non-fatal
    2
    1
    1
    Period 2
    Period 2 title
    Treatment period 2
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Treatment Period 2: izokibep 40mg Q2W
    Arm description
    		 Subject who completed izokibep 40 mg in treatment period 1 continued to receive lower dose izokibep 40mg SC injection Q2W from Week 16 to Week 44 in treatment period 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INN: izokibep
    Investigational medicinal product code
    ABY-035
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received lower dose izokibep 40 mg SC injection Q2W.

    Arm title
    		 Treatment Period 2: izokibep 80 mg Q2W
    Arm description
    		 Subject who completed izokibep 80 mg in treatment period 1 continued to receive higher dose izokibep 80 mg Q2W from Week 16 to Week 44 in treatment period 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INN: izokibep
    Investigational medicinal product code
    ABY-035
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received higher dose izokibep 80 mg SC injection Q2W.

    Arm title
    		 Treatment Period 2: Placebo/izokibep 80 mg
    Arm description
    		 Subject who received placebo in treatment period 1 switched to higher dose izokibep 80 mg Q2W from Week 16 to Week 44 in treatment period 2.
    Arm type
    		 Experimental

    Investigational medicinal product name
    INN: izokibep
    Investigational medicinal product code
    ABY-035
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received placebo in treatment period 1 switched to higher dose izokibep 80 mg Q2W from Week 16 to Week 44 in treatment period 2.

    Number of subjects in period 2
    		Treatment Period 2: izokibep 40mg Q2W Treatment Period 2: izokibep 80 mg Q2W Treatment Period 2: Placebo/izokibep 80 mg
    Started
    42
    46
    43
    Completed
    39
    44
    40
    Not completed
    3
    2
    3
         Consent withdrawn by subject
    1
    -
    1
         Others
    -
    -
    1
         Adverse event
    -
    1
    1
         Unspecified
    2
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Treatment Period 1: izokibep 40 mg Q2W
    Reporting group description
    		 Subjects received lower dose izokibep 40 mg subcutaneously (SC) every 2 weeks (Q2W) during treatment period 1 which spanned weeks 0 to 16.

    Reporting group title
    Treatment Period 1: izokibep 80 mg Q2W
    Reporting group description
    		 Subjects received higher dose izokibep 80 mg SC injection Q2W during treatment period 1 which spanned weeks 0 to 16.

    Reporting group title
    Treatment Period 1: Placebo
    Reporting group description
    		 Subject received matched placebo SC injection Q2W from Week 0 through Week 14.

    Reporting group values
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo Total
    Number of subjects
    		 44 47 44 135
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 47.6 ( 12.5 ) 50.1 ( 10.9 ) 47.6 ( 12.6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 23 28 22 73
        Male
    		 21 19 22 62
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 1 1 0 2
        Not Hispanic or Latino
    		 43 46 44 133
    Race
    Units: Subjects
        White
    		 44 47 44 135

    End points

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    End points reporting groups
    Reporting group title
    Treatment Period 1: izokibep 40 mg Q2W
    Reporting group description
    		 Subjects received lower dose izokibep 40 mg subcutaneously (SC) every 2 weeks (Q2W) during treatment period 1 which spanned weeks 0 to 16.

    Reporting group title
    Treatment Period 1: izokibep 80 mg Q2W
    Reporting group description
    		 Subjects received higher dose izokibep 80 mg SC injection Q2W during treatment period 1 which spanned weeks 0 to 16.

    Reporting group title
    Treatment Period 1: Placebo
    Reporting group description
    		 Subject received matched placebo SC injection Q2W from Week 0 through Week 14.
    Reporting group title
    Treatment Period 2: izokibep 40mg Q2W
    Reporting group description
    		 Subject who completed izokibep 40 mg in treatment period 1 continued to receive lower dose izokibep 40mg SC injection Q2W from Week 16 to Week 44 in treatment period 2.

    Reporting group title
    Treatment Period 2: izokibep 80 mg Q2W
    Reporting group description
    		 Subject who completed izokibep 80 mg in treatment period 1 continued to receive higher dose izokibep 80 mg Q2W from Week 16 to Week 44 in treatment period 2.

    Reporting group title
    Treatment Period 2: Placebo/izokibep 80 mg
    Reporting group description
    		 Subject who received placebo in treatment period 1 switched to higher dose izokibep 80 mg Q2W from Week 16 to Week 44 in treatment period 2.

    Primary: American College of Rheumatology Criteria (ACR50) Response Rate at Visit 9 (Week 16) for Izokibep 80 mg vs Placebo

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    End point title
    		 American College of Rheumatology Criteria (ACR50) Response Rate at Visit 9 (Week 16) for Izokibep 80 mg vs Placebo [1]
    End point description
    ACR 50 responders are subjects with at least 50% improvement from baseline in tender joint count, swollen joint count, and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index which measures subjects perceived degree of difficulty performing daily activities, acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP), Subject's Assessment of Pain-Visual Analog Scale (VAS), Subject's Global Assessment of Disease Activity, and Physician's Global Assessment of Disease Activity. Full analysis set (FAS) cohort included all randomized subjects with at least 1 documented application of the investigational medical product (IMP) and at least one post-Baseline ACR efficacy data available for the clinical trial. Number of subjects (responders) who achieved 50% improvement based on ACR50 response rate for Izokibep 80 mg vs placebo were reported.
    End point type
    Primary
    End point timeframe
    At Week 16
    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: Data was planned to be reported only for Higher dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    47
    44
    Units: Subjects
        At Week 16
    22
    6
    Statistical analysis title
    		 Higher Dose (80 mg) vs Placebo
    Comparison groups
    Treatment Period 1: izokibep 80 mg Q2W v Treatment Period 1: Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0006
    Method
    		 Regression, Cox
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    6.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.31
         upper limit
    		 20.91

    Primary: ACR50 Response Rate at Visit 7 (Week 12) for Izokibep 80 mg vs Placebo

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    End point title
    		 ACR50 Response Rate at Visit 7 (Week 12) for Izokibep 80 mg vs Placebo [2]
    End point description
    ACR50 responders are subjects with at least 50% improvement from baseline in tender joint count swollen joint count , and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index which measures subjects perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, subjects Assessment of Pain-Visual Analog Scale, subjects Global Assessment of Disease Activity, and Physician's Global Assessment of Disease Activity. FAS cohort included all randomized subjects with at least 1 documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Number of subjects (responders) who achieved 50% improvement based on ACR50 response rate at V7 (Week 12) for izokibep 80 mg vs Placebo were reported.
    End point type
    Primary
    End point timeframe
    At Week 12
    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: Data was planned to be reported only for Higher dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    47
    44
    Units: Subjects
        At Week 12
    21
    3
    Statistical analysis title
    		 Higher Dose (80 mg) vs Placebo
    Comparison groups
    Treatment Period 1: izokibep 80 mg Q2W v Treatment Period 1: Placebo
    Number of subjects included in analysis
    91
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Regression, Cox
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    14.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.17
         upper limit
    		 52.92

    Secondary: ACR20/70 Response Rate at Visit 9/Visit 7 (Week 16/12) for Izokibep 80 mg vs Placebo

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    End point title
    		 ACR20/70 Response Rate at Visit 9/Visit 7 (Week 16/12) for Izokibep 80 mg vs Placebo [3]
    End point description
    ACR20/70 responders are subjects with at least 20% and 70% improvement from baseline in tender joint count, swollen joint count, and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index which measures subjects perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Subject's Assessment of Pain-VAS, Subject's Global Assessment of Disease Activity, and Physician's Global Assessment of Disease Activity. FAS cohort included all randomized subjects with at least one documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Number of subjects (responders) who achieved 20% and 70% improvement in ACR 20/70 response rate for izokibep 80 mg vs Placebo was reported.
    End point type
    Secondary
    End point timeframe
    At Week 12 and 16
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be reported only for Higher dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    47
    44
    Units: Subjects
        At Week 12: ACR 20
    37
    17
        At Week 16: ACR 20
    34
    13
        At Week 12: ACR 70
    7
    2
        At Week 16: ACR 70
    8
    2
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Achieved Minimal Disease Activity (MDA) at Visit 9/Visit 7 (Week 16/12) for Izokibep 80 mg vs Placebo

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    End point title
    		 Percentage of Subjects who Achieved Minimal Disease Activity (MDA) at Visit 9/Visit 7 (Week 16/12) for Izokibep 80 mg vs Placebo [4]
    End point description
    MDA is considered achieved when 5 of the following 7 criteria are met: <=1 tender joint in the TJC68; <=1 swollen joint in the SJC66; PASI <=1 or BSA-PsO <=3%; Subject's pain assessment <=15 mm VAS; Subject's global assessment of DA <=20 mm VAS; and HAQ-DI <=0.5; Tender entheseal points <=1 site out of six sites included in the LEI. FAS cohort included all randomized subjects with at least one documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Here, “number of subjects analysed” signifies subjects who were evaluable for this endpoint. n=number analysed signifies subjects who were evaluable at specific timepoint. Percentage of subjects who achieved MDA at Visit 9/Visit 7 (Week 16/12) for Izokibep 80 mg vs Placebo were reported.
    End point type
    Secondary
    End point timeframe
    At Week 12 and 16
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data was planned to be reported only for Higher dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    46
    43
    Units: Percentage of Subjects
    number (not applicable)
        At Week 12 (n=46,42)
    17.4
    2.4
        At Week 16 (n=46,43)
    34.8
    4.7
    No statistical analyses for this end point

    Secondary: ACR20/50/70 Response Rate at Visit 9/Visit 7 (Week 16/12) for Izokibep 40 mg vs Placebo

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    End point title
    		 ACR20/50/70 Response Rate at Visit 9/Visit 7 (Week 16/12) for Izokibep 40 mg vs Placebo [5]
    End point description
    ACR20/50/70 responders are subjects with at least 20%, 50% and 70% improvement from baseline in tender joint count, swollen joint count, and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index which measures subjects perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Patient's Assessment of Pain-VAS, Patient's Global Assessment of Disease Activity, and Physician's Global Assessment of Disease Activity. FAS cohort included all randomized subjects with at least one documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Here, “number of subjects analysed” signifies subjects who were evaluable for this endpoint. Number of subjects (responders) who achieved 20%, 50% and 70% improvement in ACR20/50/70 response rate at Week 12 and 16 for Izokibep 40 mg vs Placebo was reported.
    End point type
    Secondary
    End point timeframe
    At Week 12 and 16
    Notes
    [5] - 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: Data was planned to be reported only for Lower dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    44
    44
    Units: Subjects
        At Week 12: ACR 20
    29
    17
        At Week 16: ACR 20
    27
    13
        At Week 12: ACR 50
    17
    3
        At Week 16: ACR 50
    19
    6
        At Week 12: ACR 70
    10
    2
        At Week 16: ACR 70
    12
    2
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Achieved MDA at Visit 9/Visit 7 (Week 16/12) for Izokibep 40 mg vs Placebo

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    End point title
    		 Percentage of Subjects who Achieved MDA at Visit 9/Visit 7 (Week 16/12) for Izokibep 40 mg vs Placebo [6]
    End point description
    MDA is considered achieved when 5 of the following 7 criteria are met: <=1 tender joint in the TJC68; <=1 swollen joint in the SJC66; PASI <=1 or BSA-PsO <=3%; Subject's entheseal points <=1 site out of six sites included in the LEI. FAS cohort included all randomized subjects with at least one documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Here, “number of subjects analysed” signifies subjects who were evaluable for this endpoint. Percentage of subjects who achieved MDA at Week 12 and 16 for Izokibep 40 mg vs Placebo was reported.
    End point type
    Secondary
    End point timeframe
    At Week 12 and Week 16
    Notes
    [6] - 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: Data was planned to be reported only for Lower dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    43
    43
    Units: Percentage of Subjects
    number (not applicable)
        At Week 12 (n= 43, 42)
    20.9
    2.4
        At Week 16 (n=42, 43)
    38.1
    4.7
    No statistical analyses for this end point

    Secondary: ACR20/50/70 Response Rate at Visit 5 (Week 8) for Izokibep 80 mg vs Placebo

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    End point title
    		 ACR20/50/70 Response Rate at Visit 5 (Week 8) for Izokibep 80 mg vs Placebo [7]
    End point description
    ACR20/50/70 responders are subjects with at least 20%, 50% and 70% improvement from baseline in for tender joint count, swollen joint count, and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index which measures subjects perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Subject's Assessment of Pain-VAS, Subject's Global Assessment of Disease Activity, and Physician's Global Assessment of Disease Activity. FAS cohort included all randomized subjects with at least one documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Number of subjects (responders) who achieved 20%, 50% and 70% improvement in ACR20/50/70 response rate at Week 8 for izokibep 80 mg vs Placebo were reported.
    End point type
    Secondary
    End point timeframe
    At Week 8
    Notes
    [7] - 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: Data was planned to be reported only for Higher dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    47
    44
    Units: Subjects
        At Week 8: ACR 20
    31
    16
        At Week 8: ACR 50
    17
    2
        At Week 8: ACR 70
    3
    1
    No statistical analyses for this end point

    Secondary: ACR20/50/70 Response Rate at Visit 5 (Week 8) for Izokibep 40 mg vs Placebo

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    End point title
    		 ACR20/50/70 Response Rate at Visit 5 (Week 8) for Izokibep 40 mg vs Placebo [8]
    End point description
    ACR20/50/70 responders are subjects with at least 20%, 50% and 70% improvement from baseline in for tender joint count, swollen joint count, and at least 3 of the 5 remaining core set measures: Health Assessment Questionnaire-Disability Index which measures subjects perceived degree of difficulty performing daily activities, acute phase reactant as measured by hsCRP, Subject's Assessment of Pain-VAS, Subject's Global Assessment of Disease Activity, and Physician's Global Assessment of Disease Activity. FAS cohort included all randomized subjects with at least one documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Number of subjects (responders) who achieved 20%, 50% and 70% improvement in ACR20/50/70 response rate at Week 8 for izokibep 40 mg vs Placebo were reported.
    End point type
    Secondary
    End point timeframe
    At Week 8
    Notes
    [8] - 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: Data was planned to be reported only for Lower dose vs Placebo arms for this endpoint.
    End point values
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    44
    44
    Units: Subjects
        At Week 8: ACR 20
    27
    16
        At Week 8: ACR 50
    13
    2
        At Week 8: ACR 70
    9
    1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects who Achieved MDA at Visit 5 (Week 8) for Izokibep 80 mg, Izokibep 40 mg and Placebo

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    End point title
    		 Percentage of Subjects who Achieved MDA at Visit 5 (Week 8) for Izokibep 80 mg, Izokibep 40 mg and Placebo
    End point description
    MDA is considered achieved when 5 of the following 7 criteria are met: <=1 tender joint in the TJC68; <=1 swollen joint in the SJC66; PASI <=1 or BSA-PsO <=3%; Subject's pain assessment <=15 mm VAS; Subject's global assessment of DA <=20 mm VAS; and HAQ-DI <=0.5; Tender entheseal points <=1 site out of six sites included in the LEI. FAS cohort included all randomized subjects with at least one documented application of the IMP and at least one post-Baseline ACR efficacy data available for the clinical trial. Here, “number of subjects analysed” signifies subjects who were evaluable for this endpoint. Percentage of subjects who achieved MDA at Week 8 for Izokibep 80 mg, Izokibep 40 mg and Placebo were reported.
    End point type
    Secondary
    End point timeframe
    At Week 8
    End point values
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo
    Number of subjects analysed
    42
    46
    41
    Units: Percentage of Subjects
        number (not applicable)
    26.2
    19.6
    2.4
    No statistical analyses for this end point

    Secondary: Plasma Concentration of Izokibep

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    End point title
    		 Plasma Concentration of Izokibep [9]
    End point description
    Plasma concentration of izokibep was reported. Pharmacokinetic (PK) Population (PhP) included all subjects with at least one PK assessment with valid data. Here, “number of subjects analysed” signifies subjects who were evaluable for this endpoint and "n" signifies subjects who were evaluable at specified timepoints. "99999" means data was not available because no subjects were available for analysis at timepoint specified in categories.
    End point type
    Secondary
    End point timeframe
    Treatment Period I: At Weeks 0, 2, 4, 8, 12 and 16; Treatment Period II: At Weeks 18, 32 and 44
    Notes
    [9] - 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: Descriptive data was reported as per plan.
    End point values
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 2: izokibep 40mg Q2W Treatment Period 1: izokibep 80 mg Q2W Treatment Period 2: izokibep 80 mg Q2W Treatment Period 2: Placebo/izokibep 80 mg
    Number of subjects analysed
    44
    24
    47
    22
    22
    Units: nanogram per milliliter (ng/mL)
    geometric mean (geometric coefficient of variation)
        Week 0 (n=44,0,47,0,0)
    0.0 ( 0.0 )
    99999 ( 99999 )
    0.0 ( 0.0 )
    99999 ( 99999 )
    99999 ( 99999 )
        Week 2 (n=41,0,41,0,0)
    1891.568 ( 77.83 )
    99999 ( 99999 )
    4057.993 ( 36.14 )
    99999 ( 99999 )
    99999 ( 99999 )
        Week 4 (n=44,0,41,0,0)
    2499.924 ( 62.79 )
    99999 ( 99999 )
    5639.367 ( 34.02 )
    99999 ( 99999 )
    99999 ( 99999 )
        Week 8 (n=21,0,20,0,0)
    3429.037 ( 49.80 )
    99999 ( 99999 )
    6836.772 ( 43.51 )
    99999 ( 99999 )
    99999 ( 99999 )
        Week 12 (n=41,0,41,0,0)
    3452.024 ( 57.69 )
    99999 ( 99999 )
    6699.973 ( 36.14 )
    99999 ( 99999 )
    99999 ( 99999 )
        Week 16 (n=41,0,41,0,0)
    3266.782 ( 46.93 )
    99999 ( 99999 )
    6310.016 ( 32.36 )
    99999 ( 99999 )
    99999 ( 99999 )
        Week 18 (n=0,24,0,22,22)
    99999 ( 99999 )
    3700.224 ( 46.92 )
    99999 ( 99999 )
    6886.234 ( 31.19 )
    4265.863 ( 40.51 )
        Week 32 (n=0,18,0,16,14)
    99999 ( 99999 )
    3680.908 ( 47.02 )
    99999 ( 99999 )
    7132.319 ( 37.55 )
    6355.536 ( 43.51 )
        Week 44 (n=0,9,0,5,6)
    99999 ( 99999 )
    2940.559 ( 73.20 )
    99999 ( 99999 )
    4698.114 ( 19.75 )
    6399.956 ( 37.72 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment Period 1: Week 0 to Week 16: Treatment Period 2: After Week 16 up to Week 48
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Treatment Period 1: izokibep 40 mg Q2W
    Reporting group description
    		 Subjects received lower dose izokibep 40 mg SC injection Q2W from Week 0 to Week 16 in treatment period 1.

    Reporting group title
    Treatment Period 1: izokibep 80 mg Q2W
    Reporting group description
    		 Subjects received higher dose izokibep 80 mg SC injection Q2W from Week 0 to Week 16 treatment period 1.

    Reporting group title
    Treatment Period 1: Placebo
    Reporting group description
    		 Subject received matched placebo SC injection Q2W from Week 0 through Week 14 in treatment period 1.

    Reporting group title
    Treatment Period 2: izokibep 40 mg Q2W
    Reporting group description
    		 Subject who completed izokibep 40 mg in treatment period 1 continued to receive lower dose izokibep 40 mg SC injection Q2W from Week 16 to Week 44 in treatment period 2.

    Reporting group title
    Treatment Period 2: izokibep 80 mg Q2W
    Reporting group description
    		 Subject who completed izokibep 80 mg in treatment period 1 continued to receive higher dose of izokibep 80 mg SC injection Q2W from Week 16 to Week 44 in treatment period 2.

    Reporting group title
    Treatment Period 2: Placebo/izokibep 80 mg
    Reporting group description
    		 Subject who received placebo in treatment period 1 switched to higher dose izokibep 80 mg Q2W from Week 16 to Week 44 in treatment period 2.

    Serious adverse events
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo Treatment Period 2: izokibep 40 mg Q2W Treatment Period 2: izokibep 80 mg Q2W Treatment Period 2: Placebo/izokibep 80 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    3 / 46 (6.52%)
    3 / 43 (6.98%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Vulval cancer
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament injury
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Intercostal neuralgia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Hepatitis E
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Treatment Period 1: izokibep 40 mg Q2W Treatment Period 1: izokibep 80 mg Q2W Treatment Period 1: Placebo Treatment Period 2: izokibep 40 mg Q2W Treatment Period 2: izokibep 80 mg Q2W Treatment Period 2: Placebo/izokibep 80 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    29 / 44 (65.91%)
    26 / 47 (55.32%)
    23 / 44 (52.27%)
    24 / 42 (57.14%)
    27 / 46 (58.70%)
    22 / 43 (51.16%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 47 (0.00%)
    4 / 44 (9.09%)
    0 / 42 (0.00%)
    2 / 46 (4.35%)
    1 / 43 (2.33%)
         occurrences all number
    2
    0
    4
    0
    2
    1
    Phlebitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Thrombophlebitis superficial
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Hypertensive crisis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Thrombosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    0
    1
    0
    1
    Influenza like illness
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Injection site discolouration
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Injection site erythema
         subjects affected / exposed
    8 / 44 (18.18%)
    5 / 47 (10.64%)
    0 / 44 (0.00%)
    6 / 42 (14.29%)
    5 / 46 (10.87%)
    5 / 43 (11.63%)
         occurrences all number
    13
    9
    0
    15
    11
    13
    Injection site pruritus
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Injection site reaction
         subjects affected / exposed
    12 / 44 (27.27%)
    12 / 47 (25.53%)
    0 / 44 (0.00%)
    5 / 42 (11.90%)
    7 / 46 (15.22%)
    7 / 43 (16.28%)
         occurrences all number
    41
    36
    0
    42
    34
    39
    Peripheral swelling
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    2 / 44 (4.55%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    2
    0
    0
    2
    Vaccination site pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    Asthenia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Drug intolerance
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Injection site bruising
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Injection site pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Discomfort
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Injection site urticaria
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    2
    0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    1
    1
    0
    1
    Rhinitis allergic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Paranasal cyst
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pleurisy
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Psychiatric disorders
    Adjustment disorder with depressed mood
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Depression
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    0
    1
    0
    1
    Blood cholesterol increased
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    2 / 42 (4.76%)
    2 / 46 (4.35%)
    2 / 43 (4.65%)
         occurrences all number
    1
    0
    0
    2
    2
    3
    Blood pressure increased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    2 / 42 (4.76%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    2
    0
    0
    2
    0
    1
    Dehydroepiandrosterone decreased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Gamma-glutamyltransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    3 / 46 (6.52%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    1
    0
    3
    2
    Low density lipoprotein increased
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Mean cell volume increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    2 / 47 (4.26%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Amylase increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Lipase increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    2
    0
    2
    1
    Red blood cell count increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    0
    Body temperature increased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Transaminases increased
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Injury, poisoning and procedural complications
    Meniscus injury
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Thermal burn
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Vaccination complication
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    2 / 44 (4.55%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    3
    3
    0
    1
    0
    Arthropod sting
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Ligament sprain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    0
    Ligament injury
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Ulna fracture
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Tricuspid valve incompetence
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Post herpetic neuralgia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Headache
         subjects affected / exposed
    0 / 44 (0.00%)
    4 / 47 (8.51%)
    4 / 44 (9.09%)
    1 / 42 (2.38%)
    4 / 46 (8.70%)
    2 / 43 (4.65%)
         occurrences all number
    0
    6
    4
    1
    4
    2
    Sciatica
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Tension headache
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Intercostal neuralgia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia of chronic disease
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Leukopenia
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Lymphadenopathy
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Neutropenia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Lymphopenia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    1 / 44 (2.27%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    2
    1
    1
    0
    0
    Poikilocytosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Vertigo
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Vertigo positional
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 47 (4.26%)
    3 / 44 (6.82%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    3
    0
    0
    1
    Flatulence
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Abdominal hernia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Abdominal pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Hypertransaminasaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Steatohepatitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Madarosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Papule
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Rash pruritic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    1
    0
    Skin lesion inflammation
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Acne
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Nail fold inflammation
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Skin maceration
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Renal and urinary disorders
    Cystitis noninfective
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Pollakiuria
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    Bursitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Neck pain
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Intervertebral disc disorder
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Osteoarthritis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    2 / 46 (4.35%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    2
    0
    Muscle contracture
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    Spinal pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Tendonitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Back pain
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    3 / 42 (7.14%)
    2 / 46 (4.35%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    3
    2
    3
    Arthralgia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    3 / 42 (7.14%)
    1 / 46 (2.17%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    1
    3
    1
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 47 (2.13%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    Cystitis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Herpes zoster
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    1
    0
    0
    1
    0
    1
    Laryngitis
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 44 (2.27%)
    2 / 47 (4.26%)
    0 / 44 (0.00%)
    3 / 42 (7.14%)
    4 / 46 (8.70%)
    2 / 43 (4.65%)
         occurrences all number
    1
    2
    0
    3
    4
    2
    Oral herpes
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    2 / 46 (4.35%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    0
    0
    2
    0
    Pulpitis dental
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Upper respiratory tract infection
    alternative assessment type: Systematic
         subjects affected / exposed
    2 / 44 (4.55%)
    3 / 47 (6.38%)
    1 / 44 (2.27%)
    3 / 42 (7.14%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    2
    3
    1
    3
    1
    0
    Vulvovaginal candidiasis
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    Corona virus infection
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 47 (2.13%)
    2 / 44 (4.55%)
    2 / 42 (4.76%)
    3 / 46 (6.52%)
    2 / 43 (4.65%)
         occurrences all number
    1
    1
    2
    2
    3
    2
    Gastroenteritis viral
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    1 / 46 (2.17%)
    2 / 43 (4.65%)
         occurrences all number
    0
    0
    0
    1
    1
    2
    Erysipelas
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Gastrointestinal infection
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Groin abscess
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    Tonsillitis
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 44 (2.27%)
    2 / 47 (4.26%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 47 (4.26%)
    2 / 44 (4.55%)
    0 / 42 (0.00%)
    2 / 46 (4.35%)
    0 / 43 (0.00%)
         occurrences all number
    0
    2
    2
    0
    4
    0
    Hyperkalaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 47 (4.26%)
    2 / 44 (4.55%)
    4 / 42 (9.52%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    3
    2
    2
    10
    2
    0
    Hypocalcaemia
    alternative assessment type: Systematic
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    Impaired fasting glucose
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    1 / 44 (2.27%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Dyslipidaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    0 / 46 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    Iron deficiency
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    0 / 42 (0.00%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    0 / 47 (0.00%)
    0 / 44 (0.00%)
    1 / 42 (2.38%)
    1 / 46 (2.17%)
    0 / 43 (0.00%)
         occurrences all number
    0
    0
    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
    25 Nov 2020
    Protocol amendment 1: Optimization of dosing regimen in Treatment Period II The bi-weekly dosing frequency was maintained after trial Week 16 and was not changed to four-weekly dosing administration. This Amendment was based on the data analysis of the clinical trial ABY-035-002 (EudraCT No. 2017-001615-36) and the updated ABY-035 PK/PD model. In consequence, the following aspects also changed: To allow for bi-weekly IMP administration, 7 additional trial visits were introduced. Visit 9a (Week 18) was added with IMP administration and one-hour supervision period. In addition, two weeks after the main visits (visit 10, 11, 12, 13, 14, 15 and 16) 6 additional visits (visits 10a, 11a, 12a, 13a, 14a and 15a) were performed to record IMP administration, adverse events, adverse events of special interest and concomitant medication. The one-hour supervision period after IMP administration at V11 (Week 24) was removed as subjects had already – as for the first 4 trial weeks – 3 one-hour supervision periods. It was therefore ensured that subjects who switched from Placebo to ABY-035 at Week 16 had the same level of safety surveillance as subjects exposed to ABY-035 from trial start. Because the End of Study (EoT) Visit occurred 2 weeks after the last IMP administration, the EoT was changed from Week 48 to Week 46. At Week 48 was an additional safety follow-up via a phone call (FUS).
    24 Sep 2021
    Protocol Amendment 2: Premature termination of Treatment Period II: - The clinical trial was prematurely terminated because a detailed analysis of the data from the recently completed phase II psoriasis trial with izokibep and data from other IL-17 inhibitors in psoriatic arthritis and other diseases with inflammatory joint conditions suggest that higher doses/dosing regimens than currently being studied in the protocol may be necessary to improve patient outcomes. Thus, the premature treatment termination during Treatment Period II had the consequence of omissions of trial visits during Treatment Period II and changes in the timing of one trial visit during the follow-up period for patients still ongoing at the timepoint of the amendment. - Modification of trial analyses due to premature study termination. - Change in imputation method. - Pharmacokinetic (PK) analysis. - Update of Patient Information and Informed Consent Form.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    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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