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    Clinical Trial Results:
    A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, ACTIVE REFERENCE (ADALIMUMAB) STUDY EVALUATING THE EFFICACY AND SAFETY OF BIMEKIZUMAB IN THE TREATMENT OF SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS

    Summary
    EudraCT number
    		 2017-002322-20
    Trial protocol
    		 DE   GB   BE   FR   HU   ES   CZ   IT  
    Global end of trial date
    11 Jul 2022

    Results information
    Results version number
    		 v2(current)
    This version publication date
    02 Sep 2023
    First version publication date
    23 Jul 2023
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Updated the Non-serious adverse events data at 5% threshold frequency.

    Trial information

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    Trial identification
    Sponsor protocol code
    PA0010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03895203
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    UCB Biopharma SRL
    Sponsor organisation address
    Allée de la Recherche 60, Brussels, Belgium, 1070
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.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
    29 Jul 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    17 Aug 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Jul 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Demonstrate the clinical efficacy of bimekizumab administered subcutaneously (sc) compared with placebo in the treatment of subjects with active Psoriatic Arthritis (PsA), as assessed by the American College of Rheumatology 50% Improvement (ACR50) response.
    Protection of trial subjects
    Patients were closely monitored and were expected to be treated for any worsening as per investigator judgement. Moreover, rescue medication could be added if patient was not having benefit of therapy, as per investigator discretion.
    Background therapy
    		 No background therapy.
    Evidence for comparator
    		 Adalimumab
    Actual start date of recruitment
    03 Apr 2019
    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: 65
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    Czechia: 115
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 76
    Country: Number of subjects enrolled
    Hungary: 30
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Japan: 23
    Country: Number of subjects enrolled
    Poland: 276
    Country: Number of subjects enrolled
    Russian Federation: 113
    Country: Number of subjects enrolled
    Spain: 35
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    United States: 92
    Worldwide total number of subjects
    852
    EEA total number of subjects
    546
    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)
    763
    From 65 to 84 years
    89
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study started to enroll participants in April 2019 and concluded in July 2022.

    Pre-assignment
    Screening details
    		 The Participant Flow refers to the Randomized Set (RS) which consists of enrolled participants that have been randomized and Active Treatment-Blind Set (ATS) which consists of all participants who received at least 1 dose of active treatment (Bimekizumab [BKZ] or Adalimumab [ADA]) during the Active Treatment-Blind Period (ATP) (Week 16 and after).

    Period 1
    Period 1 title
    Double-Blind Treatment Period: 16 Weeks
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo during the 16-weeks Double-Blind Treatment Period (DBP).
    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
    Participants received placebo Q4W at prespecified time points.

    Arm title
    		 BKZ 160 mg Q4W
    Arm description
    		 Participants received BKZ 160 milligrams (mg) subcutaneous (SC) every 4 weeks (Q4W) during the 16-weeks DBP.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 160 mg Q4W at prespecified time points.

    Arm title
    		 ADA 40 mg Q2W
    Arm description
    		 Participants received ADA 40 mg SC every 2 weeks (Q2W) during the 16-weeks DBP.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received ADA 40 mg SC Q2W at prespecified time points.

    Number of subjects in period 1
    		Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Started
    281
    431
    140
    Enthesitis: PA0010/11 pooled population
    106
    249
    0
    Dactylitis: PA0010/11 pooled population
    47
    90
    0
    Completed
    271
    415
    137
    Not completed
    10
    16
    3
         Consent withdrawn by subject
    4
    6
    1
         PHQ-9 Score elevated
    -
    1
    -
         Adverse event, non-fatal
    2
    8
    2
         Site terminated
    -
    1
    -
         Lost to follow-up
    2
    -
    -
         Lack of efficacy
    2
    -
    -
    Period 2
    Period 2 title
    Active Treatment-Blind Period: 36 Weeks
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/BKZ 160 mg Q4W
    Arm description
    		 After the 16-weeks DBP, participants initially randomized to placebo received BKZ 160 mg SC Q4W during the 36-weeks ATP.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 160 mg Q4W at prespecified time points.

    Arm title
    		 BKZ 160 mg Q4W/BKZ 160 mg Q4W
    Arm description
    		 After the 16-weeks DBP, participants initially randomized to BKZ 160 mg continued to receive BKZ 160 mg SC Q4W during the 36-weeks ATP.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Bimekizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received BKZ 160 mg Q4W at prespecified time points.

    Arm title
    		 ADA 40 mg Q2W/ADA 40 mg Q2W
    Arm description
    		 After the 16-weeks DBP, participants initially randomized to ADA 40 mg continued to receive ADA 40 mg SC Q2W during the 36-weeks ATP.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received ADA 40 mg SC Q2W at prespecified time points.

    Number of subjects in period 2 [1]
    		Placebo/BKZ 160 mg Q4W BKZ 160 mg Q4W/BKZ 160 mg Q4W ADA 40 mg Q2W/ADA 40 mg Q2W
    Started
    271
    414
    136
    Completed
    257
    387
    125
    Not completed
    14
    27
    11
         Adverse event, serious fatal
    1
    -
    -
         Consent withdrawn by subject
    4
    9
    2
         Adverse event, non-fatal
    5
    9
    4
         Withdrawal due to Subject Decision
    1
    -
    -
         Subject Moving Out of Area
    -
    -
    1
         COVID-19 Pandemic Circumstances
    1
    -
    -
         Lost to follow-up
    1
    3
    -
         Lack of efficacy
    1
    6
    4
    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: Eligible participants who continued to receive active treatment at Week 16 (participants not on treatment at Week 16 but continued in the study were excluded) were started in ATP.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo during the 16-weeks Double-Blind Treatment Period (DBP).

    Reporting group title
    BKZ 160 mg Q4W
    Reporting group description
    		 Participants received BKZ 160 milligrams (mg) subcutaneous (SC) every 4 weeks (Q4W) during the 16-weeks DBP.

    Reporting group title
    ADA 40 mg Q2W
    Reporting group description
    		 Participants received ADA 40 mg SC every 2 weeks (Q2W) during the 16-weeks DBP.

    Reporting group values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W Total
    Number of subjects
    		 281 431 140 852
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0
        Between 18 and 65 years
    		 255 386 122 763
        >=65 years
    		 26 45 18 89
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 48.7 ± 11.7 48.5 ± 12.6 49.0 ± 12.8 -
    Sex: Female, Male
    Units: Participants
        Female
    		 154 230 69 453
        Male
    		 127 201 71 399

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo during the 16-weeks Double-Blind Treatment Period (DBP).

    Reporting group title
    BKZ 160 mg Q4W
    Reporting group description
    		 Participants received BKZ 160 milligrams (mg) subcutaneous (SC) every 4 weeks (Q4W) during the 16-weeks DBP.

    Reporting group title
    ADA 40 mg Q2W
    Reporting group description
    		 Participants received ADA 40 mg SC every 2 weeks (Q2W) during the 16-weeks DBP.
    Reporting group title
    Placebo/BKZ 160 mg Q4W
    Reporting group description
    		 After the 16-weeks DBP, participants initially randomized to placebo received BKZ 160 mg SC Q4W during the 36-weeks ATP.

    Reporting group title
    BKZ 160 mg Q4W/BKZ 160 mg Q4W
    Reporting group description
    		 After the 16-weeks DBP, participants initially randomized to BKZ 160 mg continued to receive BKZ 160 mg SC Q4W during the 36-weeks ATP.

    Reporting group title
    ADA 40 mg Q2W/ADA 40 mg Q2W
    Reporting group description
    		 After the 16-weeks DBP, participants initially randomized to ADA 40 mg continued to receive ADA 40 mg SC Q2W during the 36-weeks ATP.

    Primary: Percentage of Participants With an American College of Rheumatology (ACR) 50 response at Week 16

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    End point title
    		 Percentage of Participants With an American College of Rheumatology (ACR) 50 response at Week 16
    End point description
    ACR50 response rate: 50% or greater improvement of arthritis from Baseline. Those who met 3 conditions for improvement from Baseline met ACR50 response criteria: Tender joint count (0-68 joints) greater than or equal (≥)50% improvement; Swollen joint count (0-66 joints) ≥50% improvement; ≥50% improvement in at least 3 of 5 below: Physician global assessment of disease activity (visual analog scale [VAS] [0-100 millimeter {mm}; no symptoms to severe]), Patient global assessment of disease activity (VAS-[0-100 mm; no limitation of normal activities to very poor]), Patient assessment of pain (VAS-[0-100 mm; no pain to most severe]), Health Assessment Questionnaire-Disability Index for degree of difficulty (20 queries from 8 domains of daily living activities total scored 0-3, 0 = less disability) High-sensitivity C-reactive protein (hsCRP). Analysis set: RS. Non-responders: Those who missed ACR50 data at Week 16 or who discontinued study before Week 16 regardless of data present or not.
    End point type
    Primary
    End point timeframe
    Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    281
    431
    140
    Units: percentage of participants
        number (not applicable)
    10.0
    43.9
    45.7
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    712
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    7.082
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.583
         upper limit
    		 10.943

    Secondary: Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16

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    End point title
    		 Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16 [1]
    End point description
    HAQ-DI contains 20 items that measured degree of difficulty experienced in following 8 categories of daily living activities: dressing and grooming (2 items), arising (2 items), eating (3 items), walking (2 items), hygiene (3 items), reach (2 items), grip (3 items), and common daily activities (3 items). Each question was scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). The overall HAQ-DI total score was calculated by dividing the sum of the highest category scores (0 to 24) by the number of categories with at least 1 question answered. Total score ranges from 0 (no difficulty) to 3 (maximum difficulty). A lower HAQ-DI score indicated an improvement in function. A negative value in change from baseline indicated an improvement. RS consisted of all enrolled participants who had been randomized. Missing data and non-missing data after treatment discontinuation were imputed using reference based multiple imputation.
    End point type
    Secondary
    End point timeframe
    Baseline, 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: Descriptive statistics for ADA 40 mg reference arm for few endpoints was not calculated and reported since reference based imputation analysis method was used with Placebo as reference. Inferential Statistics for ADA 40 mg reference arm was not calculated and reported as no formal comparison was planned.
    End point values
    		 Placebo BKZ 160 mg Q4W
    Number of subjects analysed
    281
    431
    Units: score on a scale
        arithmetic mean (standard error)
    -0.0881 ± 0.0273
    -0.2567 ± 0.0208
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    712
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 Least square (LS) mean difference
    Point estimate
    -0.187
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.249
         upper limit
    		 -0.125

    Secondary: Percentage of Participants With a Psoriasis Area Severity Index (PASI) 90 response at Week 4 in the subgroup of participants with psoriasis (PSO) involving at least 3% body surface area (BSA) at Baseline

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    End point title
    		 Percentage of Participants With a Psoriasis Area Severity Index (PASI) 90 response at Week 4 in the subgroup of participants with psoriasis (PSO) involving at least 3% body surface area (BSA) at Baseline
    End point description
    The PASI90 response assessments are based on at least 90% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of average score for redness, thickness, and scaling for each of 4 body areas with score of 0 (clear) to 4 (very marked). Determining percentage of skin covered with PSO for each of body areas and converting to 0 to 6 scale. Final PASI = average redness, thickness, and scaliness of psoriatic skin lesions, multiplied by involved psoriasis area score of respective section, and weighted by percentage of person's affected skin for respective section. Minimum possible PASI score is 0 = no disease, maximum score is 72 = maximal disease. Subset of RS with psoriasis involving at least 3% BSA at Baseline. Those who have missing PASI90 data at Week 4 or who discontinued study treatment before Week 4 regardless of whether they had data or not are considered as non-responders.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    140
    217
    68
    Units: percentage of participants
        number (not applicable)
    4.3
    19.8
    7.4
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical Component Summary (PCS) at Week 16

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    End point title
    		 Change from Baseline in the Short Form 36-item Health Survey (SF-36) Physical Component Summary (PCS) at Week 16 [2]
    End point description
    SF-36:36-item generic health-related Quality of Life instrument uses recall period of 4 weeks. Questionnaire has 36 questions composing scale represent 8 domains:physical functioning;role physical;bodily pain;general health;vitality;social functioning;role emotional;mental health. Scores for 8 domains were combined into two summary scores: PCS and mental component summary (MCS) scores. Component summary scores and 8 domains have been computed raw/observed score to norm-based T-score metric (mean=50, standard deviation=10), raw score min=0(worst), max=100(best). Individual respondent’s score outside T-score range of 45 to 55 was considered outside average range and when considering group-level data, score below 47 was considered indicative of impaired functioning within health domain or dimension. Positive value in change from Baseline indicated improvement. Analysis set RS. Missing and non-missing data after treatment discontinuation imputed using reference based multiple imputation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    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: Descriptive statistics for ADA 40 mg reference arm for few endpoints was not calculated and reported since reference based imputation analysis method was used with Placebo as reference. Inferential Statistics for ADA 40 mg reference arm was not calculated and reported as no formal comparison was planned.
    End point values
    		 Placebo BKZ 160 mg Q4W
    Number of subjects analysed
    281
    431
    Units: score on a scale
        arithmetic mean (standard error)
    2.326 ± 0.478
    6.219 ± 0.402
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    712
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    4.337
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.229
         upper limit
    		 5.444

    Secondary: Percentage of Participants With a PASI90 response at Week 16 in the subgroup of participants with PSO involving at least 3% BSA at Baseline

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    End point title
    		 Percentage of Participants With a PASI90 response at Week 16 in the subgroup of participants with PSO involving at least 3% BSA at Baseline
    End point description
    The PASI90 response assessments are based on at least 90% improvement in PASI score from Baseline. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of psoriatic skin lesions, multiplied by involved psoriasis area score of respective section, and weighted by percentage of person's affected skin for respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease. Subset of RS with psoriasis involving at least 3% BSA at Baseline. Those who have missing PASI90 data at Week 16 or who discontinued study treatment before Week 16 regardless of whether they had data or not are considered as non-responders.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    140
    217
    68
    Units: percentage of participants
        number (not applicable)
    2.9
    61.3
    41.2
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    357
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    63.039
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 22.211
         upper limit
    		 178.918

    Secondary: Percentage of Participants With a Minimal Disease Activity (MDA) at Week 16

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    End point title
    		 Percentage of Participants With a Minimal Disease Activity (MDA) at Week 16
    End point description
    Participant considered having achieved MDA if participant fulfills at least 5 of following 7 criteria: Tender joint count (0-68 joints) less than or equal to (≤) 1; Swollen joint count (0-66 joints) ≤ 1; PASI ≤ 1 or BSA ≤ 3: In PASI, body divided into four parts, head and neck, upper limb, trunk and lower limbs. Each area assessed for erythema, induration and scaling, each rated on scale of 0 to 4. Total score ranges from 0 (no disease) to 72 (maximal disease)]; Patient's Assessment of Arthritis Pain ≤ 15 [VAS on scale of 0 (no pain) to 100 (severe pain)]; Patient's Global Assessment of Disease Activity ≤ 20 [VAS on scale of 0 (very well) to 100 (very poor)]; HAQ-DI score ≤ 0.5, HAQ-DI score ranges from 0 (no difficulty) to 3 (maximum difficulty); Leeds Enthesitis Index score ≤ 1 for participants with enthesitis at baseline. Analysis Set: RS. Non-responders: Who missed MDA at Week 16 or discontinued study before Week 16 regardless of data present or not.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    281
    431
    140
    Units: percentage of participants
        number (not applicable)
    13.2
    45.0
    45.0
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    712
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    5.447
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.668
         upper limit
    		 8.088

    Secondary: Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in participants with elevated hs-CRP and/or at least 1 bone erosion at Baseline at Week 16

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    End point title
    		 Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in participants with elevated hs-CRP and/or at least 1 bone erosion at Baseline at Week 16 [3]
    End point description
    The degree of joint damage was assessed using the vdHmTSS by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively. The vdHmTSS ranges from 0 to 528, with higher scores representing greater damage. The Radiographic Set (RAS) consisted of all participants in the RS who received at least 1 dose of investigational medicinal product (IMP) and have a valid radiographic image of the hands and feet (with an assessment performed by at least the 2 reviewers) at Screening. Missing data and non-missing data preceded by a study treatment discontinuation were imputed using reference based multiple imputation. Here, number of participants analyzed included RAS set with elevated hs-CRP and/or with at least one bone erosion at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 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: Descriptive statistics for ADA 40 mg reference arm for few endpoints was not calculated and reported since reference based imputation analysis method was used with Placebo as reference. Inferential Statistics for ADA 40 mg reference arm was not calculated and reported as no formal comparison was planned.
    End point values
    		 Placebo BKZ 160 mg Q4W
    Number of subjects analysed
    227
    361
    Units: score on a scale
        arithmetic mean (standard error)
    0.36 ± 0.10
    0.04 ± 0.05
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    588
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 ANOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.327
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.524
         upper limit
    		 -0.13

    Secondary: Percentage of Participants With an Enthesitis-free state in the Leeds Enthesitis Index (LEI) at Week 16 in the subgroup of participants with enthesitis at Baseline in the pooled population of PA0010 and PA0011

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    End point title
    		 Percentage of Participants With an Enthesitis-free state in the Leeds Enthesitis Index (LEI) at Week 16 in the subgroup of participants with enthesitis at Baseline in the pooled population of PA0010 and PA0011 [4]
    End point description
    Presence of enthesitis was assessed in the subgroup of participants with enthesitis by palpation on the lateral epicondyles of the humerus (elbows), medial femoral epicondyles (knees), and Achilles tendons (heels) bilaterally and scored as 0 (no tenderness) and 1 (tenderness) at Baseline. The LEI consists of 6 items, 3 for the right part and 3 for the left part of the body. LEI is derived as the sum of the enthesitis score over the 6 sites mentioned above. The total score ranges from 0 to 6, higher scores indicates greater degree of enthesitis. As pre-specified in the SAP, the subgroup of participants with enthesitis at Baseline in the pooled population of PA0010 and PA0011 (NCT03896581) were included for the analysis of outcome measure. Participants who have missing LEI at Week 16 or who discontinued study treatment before Week 16 regardless of whether they had data or not are considered as non achieving entheistis free-state.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 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: Descriptive statistics for ADA 40 mg reference arm for few endpoints was not calculated and reported since reference based imputation analysis method was used with Placebo as reference. Inferential Statistics for ADA 40 mg reference arm was not calculated and reported as no formal comparison was planned.
    End point values
    		 Placebo BKZ 160 mg Q4W
    Number of subjects analysed
    106
    249
    Units: percentage of participants
        number (not applicable)
    34.9
    49.8
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    355
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.008
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.904
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.18
         upper limit
    		 3.074

    Secondary: Percentage of Participants With a Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup of participants with dactylitis at Baseline in the pooled population of PA0010 and PA0011

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    End point title
    		 Percentage of Participants With a Dactylitis-free state based on the Leeds Dactylitis Index (LDI) at Week 16 in the subgroup of participants with dactylitis at Baseline in the pooled population of PA0010 and PA0011 [5]
    End point description
    LDI: measures dactylitis using circumference of involved digits and control digits and tenderness of involved digits. Digits affected by dactylitis are defined those with 10% difference in ratio of circumference of affected digit to contralateral digit. Control digit is either contralateral digit (digit on opposite hand or foot). Ratio of circumference between affected digit and control digit is multiplied by tenderness score for affected digit. Results from each involved digit are summed to provide final LDI score. Higher LDI indicates worse dactylitis. Tenderness score (0 = no tenderness, 1 = tender). As pre-specified in the SAP, subgroup of participants with dactylitis at Baseline in pooled population of PA0010 and PA0011 (NCT03896581) were included for analysis of outcome measure. Non achieving dactylitis free-state: who have missing LDI at Week 16 or discontinued study before Week 16 regardless of whether they have data or not.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 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: Descriptive statistics for ADA 40 mg reference arm for few endpoints was not calculated and reported since reference based imputation analysis method was used with Placebo as reference. Inferential Statistics for ADA 40 mg reference arm was not calculated and reported as no formal comparison was planned.
    End point values
    		 Placebo BKZ 160 mg Q4W
    Number of subjects analysed
    47
    90
    Units: percentage of participants
        number (not applicable)
    51.1
    75.6
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    137
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.002
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    3.437
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.559
         upper limit
    		 7.574

    Secondary: Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in the overall population at Week 16

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    End point title
    		 Change from Baseline in Van der Heijde modified Total Sharp Score (vdHmTSS) in the overall population at Week 16 [6]
    End point description
    The degree of joint damage was assessed using the vdHmTSS by quantifying the extent of bone erosions and joint space narrowing for 64 and 52 joints, respectively. The vdHmTSS ranges from 0 to 448, with higher scores representing greater damage. The RAS consisted of all participants in the RS who received at least 1 dose of IMP and have a valid radiographic image of the hands and feet (with an assessment performed by at least the 2 reviewers) at Screening. Missing data and non-missing data preceded by a study treatment discontinuation were imputed using reference based multiple imputation.
    End point type
    Secondary
    End point timeframe
    Baseline, 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: Descriptive statistics for ADA 40 mg reference arm for few endpoints was not calculated and reported since reference based imputation analysis method was used with Placebo as reference. Inferential Statistics for ADA 40 mg reference arm was not calculated and reported as no formal comparison was planned.
    End point values
    		 Placebo BKZ 160 mg Q4W
    Number of subjects analysed
    269
    420
    Units: score on a scale
        arithmetic mean (standard error)
    0.32 ± 0.09
    0.04 ± 0.04
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v BKZ 160 mg Q4W
    Number of subjects included in analysis
    689
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.281
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.452
         upper limit
    		 -0.111

    Secondary: Percentage of Participants With an American College of Rheumatology (ACR) 20 response at Week 16

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    End point title
    		 Percentage of Participants With an American College of Rheumatology (ACR) 20 response at Week 16
    End point description
    ACR20 response rate:20% or greater improvement of arthritis relative to Baseline. Those who met following 3 conditions for improvement from Baseline were classified as meeting ACR20 criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of 5 parameters: Physician global assessment of disease activity (100 mm VAS[0 = no symptoms; 100 = severe symptoms]), Patient global assessment of disease activity (100 mm VAS [0 = no limitation of normal activities; 100 = very poor]), Patient assessment of pain (100 mm VAS [0 = no pain; 100 = most severe pain]), HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, lower scores indicated less disability, hsCRP. Analysis set: RS. Non-responders: Those who missed ACR20 data at Week 16 or who discontinued study before Week 16 regardless of data present or not.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    281
    431
    140
    Units: percentage of participants
        number (not applicable)
    23.8
    62.2
    68.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants With an American College of Rheumatology (ACR) 70 response at Week 16

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    End point title
    		 Percentage of Participants With an American College of Rheumatology (ACR) 70 response at Week 16
    End point description
    ACR70 response rate: 70% or greater improvement of arthritis relative to Baseline. Participants who met following 3 conditions for improvement from Baseline were classified as meeting ACR70 response criteria: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 70% improvement in at least 3 of 5 following parameters: Physician global assessment of disease activity (100 mm VAS [0 = no symptoms;100 = severe symptoms]), Patient global assessment of disease activity (100 mm VAS [0 = no limitation of normal activities;100 = very poor]), Patient assessment of pain (100 mm VAS [0 = no pain; 100 = most severe pain]), HAQ-DI assessed degree of difficulty experienced in 8 domains of daily living activities (20 questions), its score (0-3) computed from item scores, lower scores indicated less disability, hsCRP. RS. Non-responders: Those who missed ACR70 data at Week 16 or who discontinued study before Week 16 regardless of data present or not.
    End point type
    Secondary
    End point timeframe
    Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    281
    431
    140
    Units: percentage of participants
        number (not applicable)
    4.3
    24.4
    27.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants With an Investigator Global Assessment (IGA) response defined as score of 0(clear) or 1(almost clear) AND at least a 2-grade reduction from Baseline at Week 4 in the subset of participants with psoriatic skin lesions at Baseline

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    End point title
    		 Percentage of Participants With an Investigator Global Assessment (IGA) response defined as score of 0(clear) or 1(almost clear) AND at least a 2-grade reduction from Baseline at Week 4 in the subset of participants with psoriatic skin lesions at Baseline
    End point description
    IGA measured the overall severity of PSO using the following 5-point scale and score was rated as 0 = clear (No signs of PSO; post-inflammatory hyperpigmentation may be present), 1 = almost clear (No thickening; normal to pink coloration; no to minimal focal scaling), 2 = mild (Just detectable to mild thickening; pink to light red coloration; predominately fine scaling), 3 = moderate (Clearly distinguishable to moderate thickening; dull to bright red, moderate scaling), and 4 = severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). The IGA response is defined as score of 0 (clear) or 1 (almost clear) with at least a 2-category improvement relative to Baseline. Subset of study participants in RS with psoriatic skin lesions at Baseline. Non-responders: Participants who had missing data at the Week 4 or who discontinued study treatment before or at the Week 4 regardless of whether they had data or not.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    129
    204
    62
    Units: percentage of participants
        number (not applicable)
    3.9
    28.9
    11.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants With an IGA response defined as score of 0 (clear) or 1 (almost clear) AND at least a 2-grade reduction from Baseline at Week 16 in the subset of participants with psoriatic skin lesions at Baseline

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    End point title
    		 Percentage of Participants With an IGA response defined as score of 0 (clear) or 1 (almost clear) AND at least a 2-grade reduction from Baseline at Week 16 in the subset of participants with psoriatic skin lesions at Baseline
    End point description
    IGA measured the overall severity of PSO using the following 5-point scale and score was rated as 0 = clear (No signs of PSO; post-inflammatory hyperpigmentation may be present), 1 = almost clear (No thickening; normal to pink coloration; no to minimal focal scaling), 2 = mild (Just detectable to mild thickening; pink to light red coloration; predominately fine scaling), 3 = moderate (Clearly distinguishable to moderate thickening; dull to bright red, moderate scaling), and 4 = severe (Severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions). The IGA response is defined as score of 0 (clear) or 1 (almost clear) with at least a 2-category improvement relative to Baseline. Subset of study participants in RS with psoriatic skin lesions at Baseline. Non-responders: Participants who had missing data at the Week 16 or who discontinued study treatment before or at the Week 16 regardless of whether they had data or not.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    129
    204
    62
    Units: percentage of participants
        number (not applicable)
    3.9
    50.5
    33.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants With an Enthesitis-free state based on the Spondyloarthritis Research Consortium of Canada (SPARCC) index at Week 16 in the subgroup of participants with enthesitis at Baseline

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    End point title
    		 Percentage of Participants With an Enthesitis-free state based on the Spondyloarthritis Research Consortium of Canada (SPARCC) index at Week 16 in the subgroup of participants with enthesitis at Baseline
    End point description
    Presence of enthesitis was assessed in subgroup of participants with enthesitis at Baseline. The SPARCC index measures severity of enthesitis through assessment of 16 sites, 8 for right part and 8 for left part of the body: greater trochanter (right/left), quadriceps tendon insertion into patella (right/left), patellar ligament insertion into patella and tibial tuberosity (right/left), achilles tendon insertion (right/left), plantar fascia insertion (right/left), medial and lateral epicondyles (right/left), and supraspinatus insertion (right/left). Tenderness on examination is recorded as either present (1) or absent (0) for each of 16 sites, for an mention- average range of 0 (no enthesitis) to 16 (severe enthesitis). Subset of study participants in RS with SPARCC > 0 at Baseline. Participants who had missing SPARCC at Week 16 or who discontinued study treatment before Week 16 regardless of whether they had data or not are considered as not achieving enthesitis free-state.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    90
    166
    44
    Units: percentage of participants
        number (not applicable)
    35.6
    50.0
    52.3
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Patient's Assessment of Arthritis Pain (PtAAP) at Week 16

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    End point title
    		 Change from Baseline in the Patient's Assessment of Arthritis Pain (PtAAP) at Week 16
    End point description
    The PtAAP VAS is part of the American College of Rheumatology core set of measures in arthritis. Participants assessed their arthritis pain using a VAS ranging from 0 (no pain) to 100 (most severe pain). A negative change from baseline indicates improvement. RS consisted of all enrolled participants who had been randomized. Missing data and non-missing data preceded by a study treatment discontinuation were imputed using reference based multiple imputation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    281
    431
    140
    Units: score on a scale
        arithmetic mean (standard error)
    -6.3 ± 1.5
    -23.6 ± 1.3
    -25.7 ± 2.5
    No statistical analyses for this end point

    Secondary: Percentage of Participants with treatment-emergent adverse events (TEAEs) during the study

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    End point title
    		 Percentage of Participants with treatment-emergent adverse events (TEAEs) during the study
    End point description
    An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs were defined as any AEs with an onset date on or after the date of first IMP administration and within 140 days after the final dose of IMP. The Safety Set consisted of all participants who received at least 1 dose of the IMP. The ATS consisted of all participants who received at least 1 dose of active treatment (BKZ or ADA) during the ATP (Week 16 and after).
    End point type
    Secondary
    End point timeframe
    From Baseline until Safety Follow-Up (up to Week 72)
    End point values
    		 Placebo Placebo/BKZ 160 mg Q4W BKZ 160 mg Q4W BKZ 160 mg Q4W/BKZ 160 mg Q4W ADA 40 mg Q2W ADA 40 mg Q2W/ADA 40 mg Q2W
    Number of subjects analysed
    281
    271
    431
    414
    140
    136
    Units: percentage of participants
        number (not applicable)
    49.5
    70.5
    59.6
    72.0
    59.3
    68.4
    No statistical analyses for this end point

    Secondary: Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) total score at Week 16

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    End point title
    		 Change from Baseline in Psoriatic Arthritis Impact of Disease-12 (PsAID-12) total score at Week 16
    End point description
    The PsAID-12 is a patient-reported outcome measure for assessing the impact of Psoriatic Arthritis (PsA) in 12 physical and psychological domains, including pain, fatigue, skin problems, work and/or leisure activities, functional capacity, discomfort, sleep disturbance, coping, anxiety/fear/uncertainty, embarrassment and/or shame, social participation, and depression. Each domain is assessed with a single question using a 0 to 10 numerical rating scale. Each domain score was multiplied by a weighting factor and the results were then summed to provide the total score. The total score ranged from 0 to 10, with higher scores indicating a worse status. A negative change from baseline indicates improvement. RS consisted of all enrolled participants who had been randomized. Missing data and non-missing data preceded by a study treatment discontinuation were imputed using reference based multiple imputation.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 16
    End point values
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W
    Number of subjects analysed
    281
    431
    140
    Units: score on a scale
        arithmetic mean (standard error)
    -0.53 ± 0.10
    -1.83 ± 0.09
    -2.14 ± 0.16
    No statistical analyses for this end point

    Secondary: Percentage of Participants with treatment-emergent serious adverse events (SAEs) during the study

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    End point title
    		 Percentage of Participants with treatment-emergent serious adverse events (SAEs) during the study
    End point description
    A SAE is any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in patient hospitalization or prolongation of existing hospitalization; is a congenital anomaly or birth defect; is an infection that requires treatment parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. TEAEs were defined as any AEs with an onset date on or after the date of first IMP administration and within 140 days after the final dose of IMP. The Safety Set consisted of all participants who received at least 1 dose of the IMP. The ATS consisted of all participants who received at least 1 dose of active treatment (BKZ or ADA) during the ATP (Week 16 and after).
    End point type
    Secondary
    End point timeframe
    From Baseline until Safety Follow-Up (up to Week 72)
    End point values
    		 Placebo Placebo/BKZ 160 mg Q4W BKZ 160 mg Q4W BKZ 160 mg Q4W/BKZ 160 mg Q4W ADA 40 mg Q2W ADA 40 mg Q2W/ADA 40 mg Q2W
    Number of subjects analysed
    281
    271
    431
    414
    140
    136
    Units: percentage of participants
        number (not applicable)
    1.1
    5.9
    1.9
    5.6
    1.4
    6.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants with TEAEs leading to withdrawal from IMP during the study

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    End point title
    		 Percentage of Participants with TEAEs leading to withdrawal from IMP during the study
    End point description
    An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. TEAEs were defined as any AEs with an onset date on or after the date of first IMP administration and within 140 days after the final dose of IMP. The Safety Set consisted of all participants who received at least 1 dose of the IMP. The ATS consisted of all participants who received at least 1 dose of active treatment (BKZ or ADA) during the ATP (Week 16 and after).
    End point type
    Secondary
    End point timeframe
    From Baseline until Safety Follow-Up (up to Week 72)
    End point values
    		 Placebo Placebo/BKZ 160 mg Q4W BKZ 160 mg Q4W BKZ 160 mg Q4W/BKZ 160 mg Q4W ADA 40 mg Q2W ADA 40 mg Q2W/ADA 40 mg Q2W
    Number of subjects analysed
    281
    271
    431
    414
    140
    136
    Units: percentage of participants
        number (not applicable)
    1.1
    1.8
    1.9
    2.7
    2.1
    3.7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Baseline until Safety Follow-Up (up to Week 72)
    Adverse event reporting additional description
    TEAEs were defined as any AEs with an onset date on or after the date of first IMP administration and within 140 days after the final dose of IMP. TEAEs were analyzed and reported for DBP (safety set) and ATP (ATS) separately.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo during the 16-weeks Double-Blind Treatment Period (DBP).

    Reporting group title
    BKZ 160 mg Q4W
    Reporting group description
    		 Participants received BKZ 160 milligrams (mg) subcutaneous (SC) every 4 weeks (Q4W) during the 16-weeks DBP.

    Reporting group title
    ADA 40 mg Q2W/ADA 40 mg Q2W
    Reporting group description
    		 After the 16-weeks DBP, participants initially randomized to ADA 40 mg continued to receive ADA 40 mg SC Q2W during the 36-weeks ATP.

    Reporting group title
    Placebo/BKZ 160 mg Q4W
    Reporting group description
    		 After the 16-weeks DBP, participants initially randomized to placebo received BKZ 160 mg SC Q4W during the 36-weeks ATP.

    Reporting group title
    BKZ 160 mg Q4W/BKZ 160 mg Q4W
    Reporting group description
    		 After the 16-weeks DBP, participants initially randomized to BKZ 160 mg continued to receive BKZ 160 mg SC Q4W during the 36-weeks ATP.

    Reporting group title
    ADA 40 mg Q2W
    Reporting group description
    		 Participants received ADA 40 mg SC every 2 weeks (Q2W) during the 16-weeks DBP.

    Serious adverse events
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W/ADA 40 mg Q2W Placebo/BKZ 160 mg Q4W BKZ 160 mg Q4W/BKZ 160 mg Q4W ADA 40 mg Q2W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 281 (1.07%)
    8 / 431 (1.86%)
    9 / 136 (6.62%)
    16 / 271 (5.90%)
    23 / 414 (5.56%)
    2 / 140 (1.43%)
         number of deaths (all causes)
    0
    0
    0
    1
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Enchondromatosis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    1 / 140 (0.71%)
         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
    Breast cancer stage I
         subjects affected / exposed
    1 / 281 (0.36%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia stage 0
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Colon cancer
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Reproductive system and breast disorders
    Uterine inflammation
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Uterine haemorrhage
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Vaginal prolapse
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Cervical polyp
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Respiratory, thoracic and mediastinal disorders
    Vascular disorders
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    1 / 414 (0.24%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Hypertension
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Pneumothorax
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Pleural effusion
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Schizophrenia
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Anxiety
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    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
    Meniscus injury
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 281 (0.36%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Multiple fractures
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Hip fracture
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Traumatic shock
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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 / 1
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Pubis fracture
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Road traffic accident
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Radius fracture
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure congestive
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Myocardial infarction
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Myocardial ischaemia
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Atrial fibrillation
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    1 / 414 (0.24%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Thrombotic cerebral infarction
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Ischaemic stroke
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Cerebrovascular accident
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Rectal haemorrhage
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Proctitis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Hepatobiliary disorders
    Drug-induced liver injury
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    1 / 414 (0.24%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Non-alcoholic steatohepatitis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    IgA nephropathy
         subjects affected / exposed
    1 / 281 (0.36%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperparathyroidism
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Goitre
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Haemarthrosis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    2 / 414 (0.48%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    2 / 136 (1.47%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foot deformity
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Chondropathy
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Infections and infestations
    Herpes zoster
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    1 / 140 (0.71%)
         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
         subjects affected / exposed
    0 / 281 (0.00%)
    1 / 431 (0.23%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Gangrene
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Otitis media
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    1 / 136 (0.74%)
    0 / 271 (0.00%)
    0 / 414 (0.00%)
    0 / 140 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infections
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    0 / 271 (0.00%)
    1 / 414 (0.24%)
    0 / 140 (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
    Urinary tract infections
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Cystitis
         subjects affected / exposed
    0 / 281 (0.00%)
    0 / 431 (0.00%)
    0 / 136 (0.00%)
    1 / 271 (0.37%)
    0 / 414 (0.00%)
    0 / 140 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo BKZ 160 mg Q4W ADA 40 mg Q2W/ADA 40 mg Q2W Placebo/BKZ 160 mg Q4W BKZ 160 mg Q4W/BKZ 160 mg Q4W ADA 40 mg Q2W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    34 / 281 (12.10%)
    77 / 431 (17.87%)
    15 / 136 (11.03%)
    54 / 271 (19.93%)
    82 / 414 (19.81%)
    13 / 140 (9.29%)
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    13 / 281 (4.63%)
    40 / 431 (9.28%)
    6 / 136 (4.41%)
    23 / 271 (8.49%)
    29 / 414 (7.00%)
    7 / 140 (5.00%)
         occurrences all number
    14
    44
    7
    28
    31
    8
    Oral candidiasis
         subjects affected / exposed
    0 / 281 (0.00%)
    9 / 431 (2.09%)
    1 / 136 (0.74%)
    14 / 271 (5.17%)
    19 / 414 (4.59%)
    0 / 140 (0.00%)
         occurrences all number
    0
    10
    1
    14
    26
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 281 (1.42%)
    9 / 431 (2.09%)
    3 / 136 (2.21%)
    15 / 271 (5.54%)
    20 / 414 (4.83%)
    3 / 140 (2.14%)
         occurrences all number
    5
    9
    6
    17
    20
    3
    Upper respiratory tract infection
         subjects affected / exposed
    18 / 281 (6.41%)
    22 / 431 (5.10%)
    5 / 136 (3.68%)
    12 / 271 (4.43%)
    20 / 414 (4.83%)
    3 / 140 (2.14%)
         occurrences all number
    18
    25
    7
    15
    21
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jan 2020
    Protocol Amendment 1 (10 Jan 2020) was implemented to update the completed and ongoing studies information, clarify study procedures, update the description of the IMP, and to apply a minimum percentage for enrollment of study participants who had elevated hs-CRP and/or have at least 1 bone erosion at Screening.
    22 Feb 2021
    Protocol Amendment 2 (22 Feb 2021) was implemented to modify the secondary variables and fixed sequence testing procedure, update the statistical section, and make other procedural clarifications.

    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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