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    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled, parallel group, phase III multicenter study of intravenous secukinumab to compare efficacy at 16 weeks with placebo and to assess safety and tolerability up to 52 weeks in subjects with active Psoriatic Arthritis

    Summary
    EudraCT number
    		 2019-001176-11
    Trial protocol
    		 BG   GR  
    Global end of trial date
    17 May 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 May 2023
    First version publication date
    25 May 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CAIN457P12302
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04209205
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharmac AG  , 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharmac AG  , 41 613241111, Novartis.email@Novartis.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
    17 May 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 May 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Demonstrate that the efficacy of i.v. secukinumab at Week 16 was superior to placebo in subjects with active PsA based on the proportion of patients achieving an ACR50 response.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Jan 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
    Brazil: 9
    Country: Number of subjects enrolled
    Bulgaria: 20
    Country: Number of subjects enrolled
    Colombia: 14
    Country: Number of subjects enrolled
    Czechia: 49
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    Guatemala: 12
    Country: Number of subjects enrolled
    India: 12
    Country: Number of subjects enrolled
    Malaysia: 6
    Country: Number of subjects enrolled
    Philippines: 15
    Country: Number of subjects enrolled
    Poland: 47
    Country: Number of subjects enrolled
    Russian Federation: 11
    Country: Number of subjects enrolled
    South Africa: 63
    Country: Number of subjects enrolled
    Thailand: 18
    Country: Number of subjects enrolled
    Turkey: 1
    Country: Number of subjects enrolled
    United States: 100
    Worldwide total number of subjects
    381
    EEA total number of subjects
    120
    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)
    335
    From 65 to 84 years
    46
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 479 participants were screened and and 381 were randomized.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 AIN457 6 mg/kg - 3 mg/kg i.v.
    Arm description
    		 AIN457 6 mg/kg i.v. infusion at baseline, followed by AIN457 3 mg/kg i.v. infusion every 4 weeks starting at Week 4 through Week 48 (exposure through Week 52).
    Arm type
    		 Experimental

    Investigational medicinal product name
    secukinumab
    Investigational medicinal product code
    AIN457
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    AIN457 6 mg/kg - 3 mg/kg i.v.

    Arm title
    		 Placebo to AIN457 3 mg/kg i.v.
    Arm description
    		 Matching placebo from baseline to Week 16 and switch to AIN457 3 mg/kg i.v. infusion every 4 weeks through Week 48 (exposure through Week 52).
    Arm type
    		 both placebo and experimental

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    matching placebo 6 mg/kg - 3 mg/kg i.v.

    Number of subjects in period 1
    		AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Started
    191
    190
    Completed
    173
    167
    Not completed
    18
    23
         Physician decision
    1
    1
         Subject decision
    10
    10
         Adverse event, non-fatal
    2
    3
         Protocol deviation
    -
    1
         Death - placebo not switched
    -
    1
         Adverse event - placebo not switched
    -
    1
         Lost to follow-up
    3
    1
         Progressive disease
    1
    -
         Subject decision - placebo not switched
    -
    5
         New therapy for study indication
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    AIN457 6 mg/kg - 3 mg/kg i.v.
    Reporting group description
    		 AIN457 6 mg/kg i.v. infusion at baseline, followed by AIN457 3 mg/kg i.v. infusion every 4 weeks starting at Week 4 through Week 48 (exposure through Week 52).

    Reporting group title
    Placebo to AIN457 3 mg/kg i.v.
    Reporting group description
    		 Matching placebo from baseline to Week 16 and switch to AIN457 3 mg/kg i.v. infusion every 4 weeks through Week 48 (exposure through Week 52).

    Reporting group values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v. Total
    Number of subjects
    		 191 190 381
    Age Categorical
    Units: Participants
        <65 years
    		 170 165 335
        65-74 years
    		 17 24 41
        >= 75 years
    		 4 1 5
    Sex: Female, Male
    Units: Participants
        Female
    		 104 105 209
        Male
    		 87 85 172
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 148 153 301
        Black or African American
    		 5 1 6
        Asian
    		 25 26 51
        American Indian or Alaska Native
    		 10 9 19
        More than one race
    		 3 1 4

    End points

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    End points reporting groups
    Reporting group title
    AIN457 6 mg/kg - 3 mg/kg i.v.
    Reporting group description
    		 AIN457 6 mg/kg i.v. infusion at baseline, followed by AIN457 3 mg/kg i.v. infusion every 4 weeks starting at Week 4 through Week 48 (exposure through Week 52).

    Reporting group title
    Placebo to AIN457 3 mg/kg i.v.
    Reporting group description
    		 Matching placebo from baseline to Week 16 and switch to AIN457 3 mg/kg i.v. infusion every 4 weeks through Week 48 (exposure through Week 52).

    Primary: American College of Rheumatology 50 (ACR50) response comparison between treatment groups using non-responder imputation at Week 16 (Full analysis set)

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    End point title
    		 American College of Rheumatology 50 (ACR50) response comparison between treatment groups using non-responder imputation at Week 16 (Full analysis set)
    End point description
    Percentage of participants with active psoriatic arthritis (PsA) who achieved an American College of Rheumatology 50 (ACR50) response The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP)
    End point type
    Primary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    60
    12
    Units: Percentage of responders
        arithmetic mean (confidence interval 95%)
    31.35 (24.80 to 37.90)
    6.33 (2.87 to 9.79)
    Statistical analysis title
    		 ACR50
    Comparison groups
    Placebo to AIN457 3 mg/kg i.v. v AIN457 6 mg/kg - 3 mg/kg i.v.
    Number of subjects included in analysis
    72
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Marginal difference
    Point estimate
    25.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.61
         upper limit
    		 32.43

    Secondary: American College of Rheumatology 20 (ACR20) response comparison between treatment groups using on-responder imputation at Week 16 (Full analysis set)

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    End point title
    		 American College of Rheumatology 20 (ACR20) response comparison between treatment groups using on-responder imputation at Week 16 (Full analysis set)
    End point description
    Percentage of participants with an American College of Rheumatology 20% (ACR20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦ Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]); ◦ Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦ Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦ Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦ C-Reactive Protein.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    114
    55
    Units: Percentage of responders
        arithmetic mean (confidence interval 95%)
    59.60 (52.67 to 66.52)
    29.01 (22.57 to 35.44)
    Statistical analysis title
    		 ACR20
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    169
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Marginal difference
    Point estimate
    30.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 21.14
         upper limit
    		 40.05

    Secondary: Minimal disease activity (MDA 5/7) comparison between treatment groups using on-responder imputation at Week 16 (Full analysis set)

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    End point title
    		 Minimal disease activity (MDA 5/7) comparison between treatment groups using on-responder imputation at Week 16 (Full analysis set)
    End point description
    MDA is assessed as 5 of the 7 following: ≤ 1 tender and swollen joint; entheseal count, PASI ≤ 1 or BSA ≤3%, PsA ≤ 15 and disease activity ≤ 20 (VAS) and HAQ-DI© ≤ 0.5
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    43
    10
    Units: Percentage of responders
        arithmetic mean (confidence interval 95%)
    22.45 (16.57 to 28.33)
    5.28 (2.10 to 8.46)
    Statistical analysis title
    		 MDA 5/7
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Marginal difference
    Point estimate
    17.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.48
         upper limit
    		 23.85

    Secondary: Psoriasis Area and Severity Index 90(PASi90) comparison between treatment groups using on-responder imputation at Week 16 (Full analysis set)

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    End point title
    		 Psoriasis Area and Severity Index 90(PASi90) comparison between treatment groups using on-responder imputation at Week 16 (Full analysis set)
    End point description
    Change from baseline of a 90% reduction in the PASI score for patients with a >= 3% body surface area psoriasis at baseline. Four body surface areas are evaluated (head, trunk and upper and lower limbs) for plaque, erythema, scaling and thickness. The degree of severity of each sign in each of the 4 body areas was assigned a score of 0 to 4. Scores ranged from 0 to 72 and higher scores represent worsening severity.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    49
    7
    Units: Percentage of responders
        arithmetic mean (confidence interval 95%)
    47.85 (38.15 to 57.54)
    6.46 (1.83 to 11.09)
    Statistical analysis title
    		 PASi90
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Marginal difference
    Point estimate
    41.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 30.64
         upper limit
    		 52.13

    Secondary: Psoriatic Arthritis Disease Activity Score (PASDAS) change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)

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    End point title
    		 Psoriatic Arthritis Disease Activity Score (PASDAS) change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)
    End point description
    PASDAS is a composite measure developed to assess disease activity in Psoriatic arthritis. It is calculated by utilizing seven measures: Patient reported measures (excluding mental component) (SF-36-PCS), skin, peripheral joint counts (tender and swollen joint counts), dactylitis (LDI), enthesitis (LEI), acute phase response (CRP), and patient and physician global VAS scores. Lower score indicates better outcome.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    175
    170
    Units: composite scores
        least squares mean (standard error)
    -2.24 ( 0.103 )
    -1.11 ( 0.103 )
    Statistical analysis title
    		 PASDAS
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least squares mean
    Point estimate
    -1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.38
         upper limit
    		 0.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.129

    Secondary: Health Assessment Questionnaire - Disability Index (HAQ-DI) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)

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    End point title
    		 Health Assessment Questionnaire - Disability Index (HAQ-DI) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)
    End point description
    The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire consisting of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and usual activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task are summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement in functional ability.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    181
    183
    Units: scores on a scale
        least squares mean (standard error)
    -0.39 ( 0.035 )
    0.15 ( 0.035 )
    Statistical analysis title
    		 HAQ-DI
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    364
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least squares mean
    Point estimate
    -0.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.32
         upper limit
    		 0.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.043

    Secondary: Short Form 36-Physical Component Summary (SF36-PCS) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)

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    End point title
    		 Short Form 36-Physical Component Summary (SF36-PCS) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)
    End point description
    The SF-36 is used to measure health-related quality of life with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Range of scoring is 0 -100, with higher scores indicating better health status.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    181
    182
    Units: scores on a scale
        least squares mean (standard error)
    6.47 ( 0.558 )
    2.34 ( 0.550 )
    Statistical analysis title
    		 SF36-PCS
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    363
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least squares mean
    Point estimate
    4.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.8
         upper limit
    		 5.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.676

    Secondary: Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)

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    End point title
    		 Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)
    End point description
    The FACIT-Fatigue is a 13 item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. Response scale ranges from 0-4 and the total score range is 0 - 52. Higher scores indicate better quality of life
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    181
    183
    Units: scores on a scale
        least squares mean (standard error)
    6.15 ( 0.759 )
    3.30 ( 0.750 )
    Statistical analysis title
    		 FACIT-F
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    364
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0024
    Method
    		 Mixed models analysis
    Parameter type
    		 Least squares mean
    Point estimate
    2.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.01
         upper limit
    		 4.68
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.933

    Secondary: Modified Nail Psoriasis Severity Index (mNAPSI) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)

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    End point title
    		 Modified Nail Psoriasis Severity Index (mNAPSI) score change from baseline using mixed model repeated measures (MMRM) at Week 16 (Full analysis set)
    End point description
    The mNAPSI is an instrument to assess psoriatic nail involvement. Three groups of features (onycholysis and oil-drop dyshromia, pitting and crumbling) graded on a scale from 0 to 3. The next 4 abnormalities were graded as absent or present (leukonychia, splinter hemorrhages, hyperkeratosis and red spots in the lunula). The total score is 13 and the lower score indicates a better outcome.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    124
    118
    Units: scores
        least squares mean (standard error)
    -9.25 ( 1.069 )
    -3.14 ( 1.084 )
    Statistical analysis title
    		 mNAPSI
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    242
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Least squares mean
    Point estimate
    -6.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.96
         upper limit
    		 -3.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.447

    Secondary: Percentage of participants with complete resolution of dactylitis at Week 16 using non-responder imputation (Dactylitis subset)

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    End point title
    		 Percentage of participants with complete resolution of dactylitis at Week 16 using non-responder imputation (Dactylitis subset)
    End point description
    The Leeds Dactylitis Index (LDI) measures the ratio of the circumference of the affected (swollen) digit to the circumference of the digit on the opposite hand or foot, using a minimum difference of 10% to define a dactylitic digit. The ratio of circumference is multiplied by a tenderness score, using a modification of LDI that is a binary score (1 for tender, 0 for non-tender). The LDI requires a finger circumference gauge or a dactylometer to measure digital circumference. Scores range from 0 - 20 and lower score indicating better outcome.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    48
    23
    Units: Percentage of responders
        arithmetic mean (confidence interval 95%)
    59.53 (48.96 to 70.11)
    32.05 (21.33 to 42.76)
    Statistical analysis title
    		 Dactylitis
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    71
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0003
    Method
    		 Regression, Logistic
    Parameter type
    		 Marginal difference
    Point estimate
    27.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.43
         upper limit
    		 42.55

    Secondary: Percentage of participants with complete resolution of enthesitis at Week 16 using non-responder imputation (Enthesitis subset (LEI))

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    End point title
    		 Percentage of participants with complete resolution of enthesitis at Week 16 using non-responder imputation (Enthesitis subset (LEI))
    End point description
    Enthesitis is inflammation of the enthesis which is where a a tendon or ligament attaches to the bone. The Leeds enthesitis index (LEI) is a validated index that uses 6 sites for evaluation of enthesitis: lateral epicondyle humerus L + R, proximal achilles L + R and medial condyle femur L+R. If enthesitis is present at any of the 6 sites, the subject is counted as a subject with enthesitis.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 16
    End point values
    		 AIN457 6 mg/kg - 3 mg/kg i.v. Placebo to AIN457 3 mg/kg i.v.
    Number of subjects analysed
    70
    43
    Units: Percentage of responders
        arithmetic mean (confidence interval 95%)
    55.52 (46.92 to 64.12)
    39.16 (30.14 to 48.19)
    Statistical analysis title
    		 enthesitis
    Comparison groups
    AIN457 6 mg/kg - 3 mg/kg i.v. v Placebo to AIN457 3 mg/kg i.v.
    Number of subjects included in analysis
    113
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0102
    Method
    		 Regression, Logistic
    Parameter type
    		 Marginal difference
    Point estimate
    16.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.88
         upper limit
    		 28.82

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment up to a maximum of 481 days which included an approximate follow up period of 8 weeks for AIN457 treatment group.
    Adverse event reporting additional description
    Any subjects randomized to Placebo were counted under 'Placebo' before being switched to AIN457 and under 'Any AIN457' after being switched to AIN457. A subject with multiple occurrences of an AE under one treatment is counted only once in the AE category for that treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Any AIN457
    Reporting group description
    		 Any AIN457

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Serious adverse events
    		 Any AIN457 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    22 / 374 (5.88%)
    4 / 190 (2.11%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Procedural complication
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention postoperative
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    0 / 374 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 374 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin lesion
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 374 (0.53%)
    2 / 190 (1.05%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    6 / 374 (1.60%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Perirectal abscess
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 374 (0.53%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral pharyngitis
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus inadequate control
         subjects affected / exposed
    1 / 374 (0.27%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Any AIN457 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    136 / 374 (36.36%)
    35 / 190 (18.42%)
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    8 / 374 (2.14%)
    1 / 190 (0.53%)
         occurrences all number
    8
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    11 / 374 (2.94%)
    2 / 190 (1.05%)
         occurrences all number
    11
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    12 / 374 (3.21%)
    4 / 190 (2.11%)
         occurrences all number
    13
    4
    Weight increased
         subjects affected / exposed
    10 / 374 (2.67%)
    1 / 190 (0.53%)
         occurrences all number
    10
    1
    SARS-CoV-2 test positive
         subjects affected / exposed
    12 / 374 (3.21%)
    2 / 190 (1.05%)
         occurrences all number
    13
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    12 / 374 (3.21%)
    1 / 190 (0.53%)
         occurrences all number
    13
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    12 / 374 (3.21%)
    5 / 190 (2.63%)
         occurrences all number
    15
    6
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    9 / 374 (2.41%)
    2 / 190 (1.05%)
         occurrences all number
    11
    2
    Nausea
         subjects affected / exposed
    11 / 374 (2.94%)
    2 / 190 (1.05%)
         occurrences all number
    12
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    14 / 374 (3.74%)
    3 / 190 (1.58%)
         occurrences all number
    15
    3
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    17 / 374 (4.55%)
    1 / 190 (0.53%)
         occurrences all number
    19
    1
    Bronchitis
         subjects affected / exposed
    8 / 374 (2.14%)
    0 / 190 (0.00%)
         occurrences all number
    8
    0
    COVID-19
         subjects affected / exposed
    37 / 374 (9.89%)
    7 / 190 (3.68%)
         occurrences all number
    37
    7
    Nasopharyngitis
         subjects affected / exposed
    13 / 374 (3.48%)
    3 / 190 (1.58%)
         occurrences all number
    14
    3
    Pharyngitis
         subjects affected / exposed
    9 / 374 (2.41%)
    1 / 190 (0.53%)
         occurrences all number
    10
    1
    Upper respiratory tract infection
         subjects affected / exposed
    10 / 374 (2.67%)
    6 / 190 (3.16%)
         occurrences all number
    14
    6

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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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