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    Clinical Trial Results:
    A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects with Axial Spondyloarthritis

    Summary
    EudraCT number
    2009-010643-14
    Trial protocol
    FR   DE   GB   CZ   ES   BE   NL  
    Global end of trial date
    08 Aug 2013

    Results information
    Results version number
    v1(current)
    This version publication date
    20 Apr 2016
    First version publication date
    14 Jun 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    M10-791
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00939003
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co. KG
    Sponsor organisation address
    Abbott House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4XE
    Public contact
    Global Medical Information, AbbVie, 001 800-633-9110,
    Scientific contact
    Aileen L. Pangan, MD, AbbVie, aileen.pangan@abbvie.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
    08 Aug 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Aug 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study will evaluate how well adalimumab works in the short and long term in patients with axial spondyloarthritis who are not diagnosed as having either ankylosing spondylitis or psoriatic arthritis.
    Protection of trial subjects
    Participant and/or legal guardian read and understood information provided about the study and gave written permission.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    11 Aug 2009
    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
    Netherlands: 5
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    Belgium: 30
    Country: Number of subjects enrolled
    Czech Republic: 52
    Country: Number of subjects enrolled
    France: 19
    Country: Number of subjects enrolled
    Germany: 14
    Country: Number of subjects enrolled
    United States: 18
    Country: Number of subjects enrolled
    Australia: 21
    Country: Number of subjects enrolled
    Canada: 14
    Worldwide total number of subjects
    192
    EEA total number of subjects
    139
    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)
    189
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 192 participants were enrolled at 37 study sites in Australia, Belgium, Canada, the Czech Republic, France, Germany, the Netherlands, Spain, the United Kingdom, and the US. Due to Investigator non-compliance with protocol requirements, 1 study site was closed; the 7 participants enrolled at this site were excluded from efficacy analyses.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Double-blind Placebo
    Arm description
    Participants received placebo every other week (eow) for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection/infusion in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo every other week up to Week 12.

    Arm title
    Double-blind Adalimumab
    Arm description
    Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    ABT-D2E7,Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg every other week up to Week 12.

    Number of subjects in period 1 [1]
    Double-blind Placebo Double-blind Adalimumab
    Started
    94
    91
    Completed
    92
    87
    Not completed
    2
    4
         Adverse event
             1
             1
         Lack of efficacy
             -
             1
         MRI Not Diagnostic
             1
             1
         Pregnancy
             -
             1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Full analysis set (FAS), defined as all participants who received at least one dose of blinded study drug excluding seven participants from one site due to investigator non-compliance.
    Period 2
    Period 2 title
    Open-label Treatment Period
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo/Adalimumab
    Arm description
    Participants received placebo every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.
    Arm type
    Experimental

    Investigational medicinal product name
    Open-label Adalimumab
    Investigational medicinal product code
    Other name
    ABT-D2E7,Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg every other week, Week 12 through Week 156.

    Arm title
    Adalimumab/Adalimumab
    Arm description
    Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.
    Arm type
    Experimental

    Investigational medicinal product name
    Open-label Adalimumab
    Investigational medicinal product code
    Other name
    ABT-D2E7,Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg every other week, from Week 12 through Week 144.

    Number of subjects in period 2
    Placebo/Adalimumab Adalimumab/Adalimumab
    Started
    92
    87
    Completed
    66
    62
    Not completed
    26
    25
         Exclusion criteria
             1
             -
         Adverse event
             4
             8
         Lack of efficacy
             6
             9
         Pregnancy
             1
             1
         Consent withdrawn by subject
             14
             7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Double-blind Placebo
    Reporting group description
    Participants received placebo every other week (eow) for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.

    Reporting group title
    Double-blind Adalimumab
    Reporting group description
    Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.

    Reporting group values
    Double-blind Placebo Double-blind Adalimumab Total
    Number of subjects
    94 91 185
    Age categorical
    Units: Subjects
    Age continuous
    Full analysis set, defined as all participants who received at least one dose of blinded study drug excluding seven participants from one site due to investigator non-compliance
    Units: years
        arithmetic mean (standard deviation)
    38.4 ± 10.39 37.6 ± 11.29 -
    Gender categorical
    Full analysis set, defined as all participants who received at least one dose of blinded study drug excluding seven participants from one site due to investigator non-compliance
    Units: Subjects
        Female
    54 47 101
        Male
    40 44 84

    End points

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    End points reporting groups
    Reporting group title
    Double-blind Placebo
    Reporting group description
    Participants received placebo every other week (eow) for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.

    Reporting group title
    Double-blind Adalimumab
    Reporting group description
    Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.
    Reporting group title
    Placebo/Adalimumab
    Reporting group description
    Participants received placebo every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.

    Reporting group title
    Adalimumab/Adalimumab
    Reporting group description
    Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period and then received adalimumab 40 mg subcutaneously every other week for up to 144 weeks during the open-label period.

    Subject analysis set title
    Double-blind Placebo
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Double-blind placebo every other week for 12 weeks. Safety analysis set, defined as all participants who received at least 1 dose of study drug.

    Subject analysis set title
    Double-blind Adalimumab
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Double-blind adalimumab 40 mg subcutaneously every other week for 12 weeks. Safety analysis set, defined as all participants who received at least 1 dose of study drug.

    Primary: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response

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    End point title
    Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response
    End point description
    ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 20 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units on a scale from 0 to 100) in the potential remaining domain: • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants’ ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
    End point type
    Primary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [1]
    91 [2]
    Units: Participants
    14
    33
    Notes
    [1] - FAS. Subjects with missing data at week 12 were counted as non-responders (non-responder imputation)
    [2] - FAS. Subjects with missing data at week 12 were counted as non-responders (non-responder imputation)
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Chi-squared
    Confidence interval

    Secondary: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response

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    End point title
    Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response
    End point description
    ASAS20 response was defined as improvement of ≥ 20% relative to Baseline and absolute improvement of ≥ 10 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a change for the worse of ≥ 20% and net worsening of ≥ 10 units) in the potential remaining domain: • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants’ ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [3]
    91 [4]
    Units: Participants
    29
    47
    Notes
    [3] - Full analysis set; Non-responder imputation performed.
    [4] - Full analysis set; Non-responder imputation performed.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.004
    Method
    Chi-squared
    Confidence interval

    Secondary: Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response

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    End point title
    Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response
    End point description
    The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 cm VAS) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10 cm. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from Baseline in BASDAI score.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [5]
    91 [6]
    Units: Participants
    14
    32
    Notes
    [5] - Full analysis set; Non-responder imputation performed.
    [6] - Full analysis set; Non-responder imputation performed.
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.001
    Method
    Chi-squared
    Confidence interval

    Secondary: Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score

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    End point title
    Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score
    End point description
    The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life. The SF-36 consists of 36 questions in 8 domains (limitations in physical functioning due to health problems; limitations in usual role because of physical health problems; bodily pain; general health perceptions; vitality; limitations in social functioning because of physical or emotional problems; limitations in usual role due to emotional problems; and general mental health). Two component scores can be summarized: physical and mental; domains 1-4 comprise the physical component summary of the SF-36. A transformed summary score is calculated ranging from 0 to 100 where higher scores indicate a higher level of functioning. A positive change from Baseline score indicates an improvement.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    93 [7]
    91 [8]
    Units: units on a scale
        arithmetic mean (standard deviation)
    2 ± 7.04
    5.5 ± 8.98
    Notes
    [7] - Full analysis set with available data
    [8] - Full analysis set with available data
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    ANCOVA model adjusting for Baseline value with treatment as a factor.
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    184
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.001
    Method
    ANCOVA
    Confidence interval

    Secondary: Number of Participants Achieving ASAS Partial Remission

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    End point title
    Number of Participants Achieving ASAS Partial Remission
    End point description
    ASAS partial remission is an absolute score of < 20 units on a 0 to 100 scale for each of the four following domains: • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [9]
    91 [10]
    Units: Participants
    5
    15
    Notes
    [9] - Full analysis set; Non-responder imputation performed
    [10] - Full analysis set; Non-responder imputation performed
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.014
    Method
    Chi-squared
    Confidence interval

    Secondary: Number of Participants Achieving an ASAS5/6 Response

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    End point title
    Number of Participants Achieving an ASAS5/6 Response
    End point description
    ASAS5/6 response is a 20% improvement in five out of the following six domains: • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none) to 10 (very severe/2 hours or more duration). • Spinal mobility, measured from the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility); • C-reactive protein level (lower levels indicate less inflammation).
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [11]
    91 [12]
    Units: Participants
    6
    28
    Notes
    [11] - Full analysis set; Non-responder imputation performed
    [12] - Full analysis set; Non-responder imputation performed
    Statistical analysis title
    Statistical Analysis 1
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Chi-squared
    Confidence interval

    Secondary: Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S)

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    End point title
    Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S)
    End point description
    Health Assessment Questionnaire modified for spondyloarthropathies (HAQ-S) is a self-reported measure to assess the physical function and health-related quality of life. The Disability Index (DI) of HAQ-S is calculated as the mean of the following 8 category scores (range: 0 [without any difficulty] to 3 [unable to do]): Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Five additional items in the functional status measure were included in the HAQ-S, including carrying heavy packages, sitting for long periods, able to work at a flat topped table, and (if the participant had a driver's license or a car) able to look in the rear view mirror and able to turn head to drive in reverse. The overall score ranges from 0 (no disability) to 3 (three very severe, high-dependency disability). Negative mean changes from Baseline in the overall score indicate improvement.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [13]
    91 [14]
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.1 ± 0.42
    -0.3 ± 0.49
    Notes
    [13] - FAS: non-missing Baseline and ≥1 non-missing post-baseline value; Last observation carried forward
    [14] - FAS: non-missing Baseline and ≥1 non-missing post-baseline value; Last observation carried forward
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    ANCOVA model adjusting for Baseline value with treatment as a factor.
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.027
    Method
    ANCOVA
    Confidence interval

    Secondary: Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)

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    End point title
    Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)
    End point description
    C-reactive protein (CRP) is considered an efficacy variable for the axial spondyloarthritis indication. It is a general marker of inflammation that is sensitive to acute changes in inflammatory response. Higher levels indicate more inflammation.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    73 [15]
    70 [16]
    Units: mg/L
        arithmetic mean (standard deviation)
    -0.3 ± 6.39
    -4.7 ± 12.32
    Notes
    [15] - FAS: non-missing Baseline and ≥1 non-missing post-baseline value; Last observation carried forward
    [16] - FAS: non-missing Baseline and ≥1 non-missing post-baseline value; Last observation carried forward
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    ANCOVA model adjusting for Baseline value with treatment as a factor.
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    143
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    ANCOVA
    Confidence interval

    Secondary: Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints

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    End point title
    Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints
    End point description
    Six consecutive sacroiliac (SI) joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema using SPARCC scoring. Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema; the maximum score is 8 per slice and maximum score for 6 SI joint slices is 48. Intensity of edema: A score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice. The maximum score is 2 per slice and 12 for 6 slices. A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant. The maximum score per slice is 2 and for 6 slices 12. The total maximum score for all SI joints across 6 slices is 72.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    84 [17]
    84 [18]
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.6 ± 6.19
    -3.2 ± 8.34
    Notes
    [17] - FAS; participants with non-missing Baseline and non-missing post-baseline value were included
    [18] - FAS; participants with non-missing Baseline and non-missing post-baseline value were included
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    ANCOVA model adjusting for Baseline value with treatment as a factor.
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    168
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.003
    Method
    ANCOVA
    Confidence interval

    Secondary: Change From Baseline in SPARCC MRI Score for the Spine

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    End point title
    Change From Baseline in SPARCC MRI Score for the Spine
    End point description
    Six discovertebral units (DVU) representing the 6 most abnormal DVUs, and 3 consecutive sagittal slices at each DVU representing the most abnormal slices for that DVU were selected for scoring. Each DVU was divided into 4 quadrants and scored for the presence (1) or absence (0) of edema. The maximum score is 12 per DVU. The maximum score is 72 for 6 DVUs. If edema was present in at least 1 quadrant of a DVU slice, it was scored for intensity and depth of the edema representing that slice: A score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. The maximum score for intensity per slice is 1, per DVU is 3 and for 6 DVUs is 18. A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the surface of the endplate in any quadrant. The maximum score per slice is 1, for a DVU is 3 and for 6 DVUs is 18. The total maximum SPARCC score for all 6 DVUs is 108.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    82 [19]
    85 [20]
    Units: units on a scale
        arithmetic mean (standard deviation)
    -0.2 ± 3.35
    -1.8 ± 4.51
    Notes
    [19] - FAS; FAS; participants with non-missing Baseline and non-missing post-baseline value were included
    [20] - FAS; FAS; participants with non-missing Baseline and non-missing post-baseline value were included
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    ANCOVA model adjusting for Baseline value with treatment as a factor.
    Comparison groups
    Double-blind Placebo v Double-blind Adalimumab
    Number of subjects included in analysis
    167
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.001
    Method
    ANCOVA
    Confidence interval

    Other pre-specified: Number of Participants Reporting Adverse Events

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    End point title
    Number of Participants Reporting Adverse Events
    End point description
    Adverse events were collected at designated study visits for all participants who received at least 1 dose of study drug. The number of participants experiencing any adverse event (serious and non-serious) is summarized. For the double-blind phase of the study, adverse events are reported through Week 12.
    End point type
    Other pre-specified
    End point timeframe
    Through Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    97 [21]
    95 [22]
    Units: participants
    57
    55
    Notes
    [21] - All participants who received at least 1 dose of study drug
    [22] - All participants who received at least 1 dose of study drug
    No statistical analyses for this end point

    Other pre-specified: Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3

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    End point title
    Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade ≥ 3
    End point description
    Blood was collected for analysis at designated study visits; hematology and chemistry results were provided by a central laboratory. The number of participants with an abnormal laboratory result (higher then upper normal limit or lower than lower normal limit) meeting Common Toxicity Criteria (CTC) of Grade 3 or higher is summarized. Results for the double-blind phase phase of the study are reported through Week 12.
    End point type
    Other pre-specified
    End point timeframe
    Through Week 12
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    97 [23]
    95 [24]
    Units: Participants
    6
    4
    Notes
    [23] - All participants who received at least 1 dose of study drug
    [24] - All participants who received at least 1 dose of study drug
    No statistical analyses for this end point

    Other pre-specified: Number of Participants Achieving an ASAS20 Response During the Open-label Period

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    End point title
    Number of Participants Achieving an ASAS20 Response During the Open-label Period
    End point description
    ASAS20 response was defined as improvement of ≥ 20% relative to Baseline and absolute improvement of ≥ 10 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a change for the worse of ≥ 20% and net worsening of ≥ 10 units) in the potential remaining domain: • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Weeks 52, 104, and 156
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [25]
    91 [26]
    Units: Participants
        Week 52 (N=78, 72)
    59
    57
        Week 104 (N=74, 64)
    59
    53
        Week 156 (N=64, 58)
    53
    48
    Notes
    [25] - Full analysis set participants with available data at each time point (indicated by N)
    [26] - Full analysis set participants with available data at each time point (indicated by N)
    No statistical analyses for this end point

    Other pre-specified: Number of Participants Achieving an ASAS40 Response During the Open-label Period

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    End point title
    Number of Participants Achieving an ASAS40 Response During the Open-label Period
    End point description
    ASAS40 response was defined as improvement of ≥ 40% relative to Baseline and absolute improvement of ≥ 20 units (on a scale from 0 to 100) in ≥ 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units on a scale of 0 to 100) in the potential remaining domain: • Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); • Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); • Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); • Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Weeks 52, 104, and 156
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [27]
    91 [28]
    Units: participants
        Week 52 (N=78, 72)
    50
    42
        Week 104 (N=74, 64)
    51
    38
        Week 156 (N=64, 58)
    44
    37
    Notes
    [27] - Full analysis set participants with available data at each time point (indicated by N).
    [28] - Full analysis set participants with available data at each time point (indicated by N).
    No statistical analyses for this end point

    Other pre-specified: Number of Participants Achieving a BASDAI50 Response During the Open-label Period

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    End point title
    Number of Participants Achieving a BASDAI50 Response During the Open-label Period
    End point description
    The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 cm VAS) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10 cm. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from Baseline in BASDAI score.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Weeks 52, 104, and 156
    End point values
    Double-blind Placebo Double-blind Adalimumab
    Number of subjects analysed
    94 [29]
    91 [30]
    Units: participants
        Week 52 (N=78, 72)
    52
    42
        Week 104 (N=74, 64)
    50
    40
        Week 156 (N=64, 58)
    46
    39
    Notes
    [29] - Full analysis set participants with available data at each time point (indicated by N).
    [30] - Full analysis set participants with available data at each time point (indicated by N).
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Twelve weeks during the double blind period and up to Week 156 during the open-label period.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Double-blind Placebo
    Reporting group description
    Participants received placebo every other week for 12 weeks during the double-blind period.

    Reporting group title
    Double-blind Adalimumab
    Reporting group description
    Participants received adalimumab 40 mg subcutaneously every other week for 12 weeks during the double-blind period.

    Reporting group title
    Any Adalimumab
    Reporting group description
    Participants who received any dose of adalimumab during the 12-week double-blind period or during the 144-week open-label period.

    Serious adverse events
    Double-blind Placebo Double-blind Adalimumab Any Adalimumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 97 (1.03%)
    3 / 95 (3.16%)
    33 / 190 (17.37%)
         number of deaths (all causes)
    0
    0
    2
         number of deaths resulting from adverse events
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    0 / 97 (0.00%)
    1 / 95 (1.05%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chills
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Suicide attempt
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Breast dysplasia
         subjects affected / exposed
    0 / 97 (0.00%)
    1 / 95 (1.05%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Menorrhagia
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Incisional hernia
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laceration
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    2 / 190 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Macular degeneration
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oscillopsia
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain lower
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    0 / 190 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    0 / 97 (0.00%)
    1 / 95 (1.05%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lupus-like syndrome
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periarthritis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tendon calcification
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Goitre
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bursitis infective
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    2 / 190 (1.05%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated tuberculosis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    1 / 190 (0.53%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    Double-blind Placebo Double-blind Adalimumab Any Adalimumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    32 / 97 (32.99%)
    42 / 95 (44.21%)
    152 / 190 (80.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 97 (2.06%)
    0 / 95 (0.00%)
    9 / 190 (4.74%)
         occurrences all number
    2
    0
    11
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 97 (2.06%)
    3 / 95 (3.16%)
    7 / 190 (3.68%)
         occurrences all number
    2
    3
    12
    Fatigue
         subjects affected / exposed
    0 / 97 (0.00%)
    3 / 95 (3.16%)
    14 / 190 (7.37%)
         occurrences all number
    0
    3
    16
    Injection site erythema
         subjects affected / exposed
    0 / 97 (0.00%)
    3 / 95 (3.16%)
    6 / 190 (3.16%)
         occurrences all number
    0
    3
    7
    Injection site pain
         subjects affected / exposed
    3 / 97 (3.09%)
    1 / 95 (1.05%)
    2 / 190 (1.05%)
         occurrences all number
    3
    1
    2
    Injection site reaction
         subjects affected / exposed
    0 / 97 (0.00%)
    4 / 95 (4.21%)
    11 / 190 (5.79%)
         occurrences all number
    0
    4
    11
    Pyrexia
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 95 (2.11%)
    8 / 190 (4.21%)
         occurrences all number
    0
    2
    9
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    11 / 190 (5.79%)
         occurrences all number
    0
    0
    11
    Depression
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 95 (2.11%)
    7 / 190 (3.68%)
         occurrences all number
    0
    2
    7
    Insomnia
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 95 (2.11%)
    9 / 190 (4.74%)
         occurrences all number
    0
    3
    11
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    7 / 190 (3.68%)
         occurrences all number
    0
    0
    7
    Fall
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    6 / 190 (3.16%)
         occurrences all number
    0
    0
    7
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 97 (1.03%)
    1 / 95 (1.05%)
    6 / 190 (3.16%)
         occurrences all number
    1
    1
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 97 (1.03%)
    1 / 95 (1.05%)
    8 / 190 (4.21%)
         occurrences all number
    1
    1
    11
    Oropharyngeal pain
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    9 / 190 (4.74%)
         occurrences all number
    0
    0
    10
    Nervous system disorders
    Headache
         subjects affected / exposed
    3 / 97 (3.09%)
    6 / 95 (6.32%)
    19 / 190 (10.00%)
         occurrences all number
    3
    6
    21
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    6 / 190 (3.16%)
         occurrences all number
    0
    0
    6
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 95 (2.11%)
    9 / 190 (4.74%)
         occurrences all number
    0
    2
    10
    Constipation
         subjects affected / exposed
    3 / 97 (3.09%)
    1 / 95 (1.05%)
    2 / 190 (1.05%)
         occurrences all number
    3
    1
    2
    Diarrhoea
         subjects affected / exposed
    7 / 97 (7.22%)
    4 / 95 (4.21%)
    18 / 190 (9.47%)
         occurrences all number
    9
    5
    23
    Nausea
         subjects affected / exposed
    7 / 97 (7.22%)
    7 / 95 (7.37%)
    13 / 190 (6.84%)
         occurrences all number
    7
    7
    17
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 97 (1.03%)
    1 / 95 (1.05%)
    6 / 190 (3.16%)
         occurrences all number
    1
    1
    11
    Rash
         subjects affected / exposed
    2 / 97 (2.06%)
    2 / 95 (2.11%)
    6 / 190 (3.16%)
         occurrences all number
    2
    2
    6
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 97 (1.03%)
    1 / 95 (1.05%)
    11 / 190 (5.79%)
         occurrences all number
    1
    1
    12
    Back pain
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    13 / 190 (6.84%)
         occurrences all number
    1
    0
    15
    Bursitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    9 / 190 (4.74%)
         occurrences all number
    0
    0
    13
    Muscle spasms
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    6 / 190 (3.16%)
         occurrences all number
    1
    0
    6
    Myalgia
         subjects affected / exposed
    1 / 97 (1.03%)
    1 / 95 (1.05%)
    7 / 190 (3.68%)
         occurrences all number
    1
    1
    8
    Spondylitis
         subjects affected / exposed
    2 / 97 (2.06%)
    2 / 95 (2.11%)
    37 / 190 (19.47%)
         occurrences all number
    2
    2
    55
    Spondyloarthropathy
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    8 / 190 (4.21%)
         occurrences all number
    0
    0
    9
    Synovial cyst
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    6 / 190 (3.16%)
         occurrences all number
    0
    0
    6
    Tendonitis
         subjects affected / exposed
    0 / 97 (0.00%)
    1 / 95 (1.05%)
    6 / 190 (3.16%)
         occurrences all number
    0
    1
    6
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    6 / 190 (3.16%)
         occurrences all number
    1
    0
    6
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 97 (2.06%)
    1 / 95 (1.05%)
    31 / 190 (16.32%)
         occurrences all number
    2
    1
    38
    Cystitis
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    7 / 190 (3.68%)
         occurrences all number
    0
    0
    12
    Gastroenteritis
         subjects affected / exposed
    3 / 97 (3.09%)
    2 / 95 (2.11%)
    11 / 190 (5.79%)
         occurrences all number
    3
    2
    15
    Influenza
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 95 (2.11%)
    9 / 190 (4.74%)
         occurrences all number
    0
    2
    9
    Nasopharyngitis
         subjects affected / exposed
    3 / 97 (3.09%)
    11 / 95 (11.58%)
    52 / 190 (27.37%)
         occurrences all number
    4
    11
    81
    Oral herpes
         subjects affected / exposed
    0 / 97 (0.00%)
    2 / 95 (2.11%)
    6 / 190 (3.16%)
         occurrences all number
    0
    3
    15
    Pharyngitis
         subjects affected / exposed
    0 / 97 (0.00%)
    3 / 95 (3.16%)
    15 / 190 (7.89%)
         occurrences all number
    0
    3
    18
    Rhinitis
         subjects affected / exposed
    2 / 97 (2.06%)
    2 / 95 (2.11%)
    9 / 190 (4.74%)
         occurrences all number
    3
    2
    15
    Sinusitis
         subjects affected / exposed
    2 / 97 (2.06%)
    1 / 95 (1.05%)
    18 / 190 (9.47%)
         occurrences all number
    2
    1
    25
    Tonsillitis
         subjects affected / exposed
    2 / 97 (2.06%)
    1 / 95 (1.05%)
    9 / 190 (4.74%)
         occurrences all number
    2
    1
    15
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 97 (4.12%)
    3 / 95 (3.16%)
    19 / 190 (10.00%)
         occurrences all number
    4
    3
    33
    Urinary tract infection
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    7 / 190 (3.68%)
         occurrences all number
    1
    0
    16
    Vaginal infection
         subjects affected / exposed
    1 / 97 (1.03%)
    0 / 95 (0.00%)
    6 / 190 (3.16%)
         occurrences all number
    1
    0
    7
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 97 (0.00%)
    0 / 95 (0.00%)
    7 / 190 (3.68%)
         occurrences all number
    0
    0
    9

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    01 Aug 2011
    Extended open-label treatment to 144 weeks; added the QuantiFERON®-TB Gold Test; added yearly testing of subjects negative for purified protein derivative (PPD) at screening; added a confirmatory human leukocyte antigen-B27 (HLA-B27) test if the initial test was reported as equivocal; added an antero-posterior (AP) pelvis x-ray at week 104 for monitoring progression of disease; added tuberculosis (TB) prophylaxis non-compliance as a reason for subject discontinuation; and added clarifications and additional explanations for better understanding by the sites.

    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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