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    Clinical Trial Results:
    A Phase 3, Open-Label Study of the Safety and Efficacy of Adalimumab in Subjects With Moderate to Severe Hidradenitis Suppurativa - PIONEER (Open-Label Extension)

    Summary
    EudraCT number
    2011-003478-98
    Trial protocol
    SE   NL   HU   GR   DE   DK   CZ  
    Global end of trial date
    12 Aug 2016

    Results information
    Results version number
    v2(current)
    This version publication date
    21 Sep 2017
    First version publication date
    20 Aug 2017
    Other versions
    v1
    Version creation reason
    • Correction of full data set
    One time point in the time frame for primary endpoint 4 corrected (from Week 201 to Week 204).

    Trial information

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    Trial identification
    Sponsor protocol code
    M12-555
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01635764
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co.
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Services, AbbVie, 001 800-633-9110,
    Scientific contact
    Dawn Carlson, MD, AbbVie, dawn.carlson@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
    12 Aug 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Aug 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study to evaluate the long term safety, tolerability and efficacy of adalimumab in subjects with moderate to severe hidradenitis suppurativa (HS).
    Protection of trial subjects
    Subject read and understood the information provided about the study and gave written permission
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    12 Apr 2012
    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
    Australia: 61
    Country: Number of subjects enrolled
    Canada: 53
    Country: Number of subjects enrolled
    Czech Republic: 28
    Country: Number of subjects enrolled
    Denmark: 13
    Country: Number of subjects enrolled
    France: 37
    Country: Number of subjects enrolled
    Germany: 44
    Country: Number of subjects enrolled
    Greece: 39
    Country: Number of subjects enrolled
    Hungary: 13
    Country: Number of subjects enrolled
    Netherlands: 16
    Country: Number of subjects enrolled
    Sweden: 2
    Country: Number of subjects enrolled
    Switzerland: 16
    Country: Number of subjects enrolled
    Turkey: 2
    Country: Number of subjects enrolled
    United States: 184
    Worldwide total number of subjects
    508
    EEA total number of subjects
    192
    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)
    502
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    Subjects were evaluated for entry into Study M12-555 at the final study visit of the prior Phase 3 study in which they participated. Therefore, the Study M12-555 Baseline (Week 0) visit and administration of the first dose of study drug in Study M12-555 was performed on the same day as the final or last visit of the prior Phase 3 study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Adalimumab Every Week
    Arm description
    Adalimumab 40 mg every week.
    Arm type
    Experimental

    Investigational medicinal product name
    adalimumab
    Investigational medicinal product code
    Other name
    Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Adalimumab pre-filled syringe, administered by subcutaneous injection

    Number of subjects in period 1
    Adalimumab Every Week
    Started
    508
    Completed
    235
    Not completed
    273
         Protocol deviation
    1
         Exceed Protocol-specified Interventions
    2
         Adverse event
    46
         Lack of efficacy
    76
         Not specified
    28
         Withdrew consent
    67
         Lost to follow-up
    53

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Adalimumab Every Week
    Reporting group description
    Adalimumab 40 mg every week.

    Reporting group values
    Adalimumab Every Week Total
    Number of subjects
    508 508
    Age categorical
    Units: Subjects
    Age continuous
    Baseline characteristics provided by reporting groups defined by treatment received in prior HS study plus treatment received in M12-555.
    Units: years
        arithmetic mean (standard deviation)
    36.8 ± 11.35 -
    Gender categorical
    Baseline characteristics provided by reporting groups defined by treatment received in prior HS study plus treatment received in M12-555.
    Units: Subjects
        Female
    328 328
        Male
    180 180
    Subject analysis sets

    Subject analysis set title
    EW/EW/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received adalimumab 40 mg every week (EW) in both Period A and Period B of the prior Phase 3 studies.

    Subject analysis set title
    EW/EOW/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received adalimumab 40 mg every week (EW) in Period A and 40 mg every other week (EOW) in Period B in the prior Phase 3 studies.

    Subject analysis set title
    EW/PBO/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received adalimumab 40 mg every week (EW) in Period A and placebo in Period B in the prior Phase 3 studies.

    Subject analysis set title
    PBO/EW/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received placebo in Period A and adalimumab 40 mg every week (EW) in Period B in prior phase 3 study M11-313.

    Subject analysis set title
    PBO/PBO/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received placebo in both Period A and Period B in prior phase 3 study M11-810.

    Subject analysis sets values
    EW/EW/EW EW/EOW/EW EW/PBO/EW PBO/EW/EW PBO/PBO/EW
    Number of subjects
    88
    90
    92
    115
    123
    Age categorical
    Units: Subjects
    Age continuous
    Baseline characteristics provided by reporting groups defined by treatment received in prior HS study plus treatment received in M12-555.
    Units: years
        arithmetic mean (standard deviation)
    35.5 ± 10.27
    36.1 ± 10.5
    36.5 ± 11.06
    38.5 ± 11.92
    37 ± 12.28
    Gender categorical
    Baseline characteristics provided by reporting groups defined by treatment received in prior HS study plus treatment received in M12-555.
    Units: Subjects
        Female
    56
    60
    50
    79
    83
        Male
    32
    30
    42
    36
    40

    End points

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    End points reporting groups
    Reporting group title
    Adalimumab Every Week
    Reporting group description
    Adalimumab 40 mg every week.

    Subject analysis set title
    EW/EW/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received adalimumab 40 mg every week (EW) in both Period A and Period B of the prior Phase 3 studies.

    Subject analysis set title
    EW/EOW/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received adalimumab 40 mg every week (EW) in Period A and 40 mg every other week (EOW) in Period B in the prior Phase 3 studies.

    Subject analysis set title
    EW/PBO/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received adalimumab 40 mg every week (EW) in Period A and placebo in Period B in the prior Phase 3 studies.

    Subject analysis set title
    PBO/EW/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received placebo in Period A and adalimumab 40 mg every week (EW) in Period B in prior phase 3 study M11-313.

    Subject analysis set title
    PBO/PBO/EW
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    All participants who received placebo in both Period A and Period B in prior phase 3 study M11-810.

    Primary: Percentage of Participants in the EW/EW/EW, EW/EOW/EW, and EW/PBO/EW Analysis Populations Achieving Clinical Response Per Hidradenitis Suppurativa Clinical Response (HiSCR) at Each Visit

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    End point title
    Percentage of Participants in the EW/EW/EW, EW/EOW/EW, and EW/PBO/EW Analysis Populations Achieving Clinical Response Per Hidradenitis Suppurativa Clinical Response (HiSCR) at Each Visit [1]
    End point description
    Clinical response per HiSCR defined as percent reduction from baseline of the prior phase 3 study in the abscess and inflammatory nodule ≥ 50% (AN50) with no increase in the abscess count and no increase in the draining fistula count. Last Observation Carried Forward (LOCF): The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Weeks 2 (first dose of adalimumab in prior phase 3 study), 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EW/EW EW/EOW/EW EW/PBO/EW
    Number of subjects analysed
    88 [2]
    90 [3]
    92 [4]
    Units: percentage of particpants
    number (not applicable)
        Week 2 (n=88,88,91)
    34.1
    39.8
    34.1
        Week 4 (n=88,90,92)
    38.6
    41.1
    40.2
        Week 8 (n=88,90,92)
    51.1
    48.9
    47.8
        Week 12 (n=88,90,92)
    52.3
    55.6
    51.1
        Week 16 (n=88,90,92)
    50
    56.7
    45.7
        Week 20 (n=88,90,92)
    56.8
    45.6
    45.7
        Week 24 (n=88,90,92)
    48.9
    47.8
    42.4
        Week 36 (n=88,90,92)
    62.5
    54.4
    52.2
        Week 48 (n=88,90,92)
    58
    55.6
    58.7
        Week 60 (n=88,90,92)
    62.5
    57.8
    58.7
        Week 72 (n=88,90,92)
    59.1
    61.1
    53.3
        Week 84 (n=88,90,92)
    56.8
    56.7
    55.4
        Week 96 (n=88,90,92)
    56.8
    54.4
    53.3
        Week 108 (n=88,90,92)
    60.2
    56.7
    53.3
        Week 120 (n=88,90,92)
    56.8
    52.2
    45.7
        Week 132 (n=88,90,92)
    52.3
    52.2
    50
        Week 144 (n=88,90,92)
    51.1
    54.4
    52.2
        Week 156 (n=88,90,92)
    48.9
    52.2
    50
        Week 168 (n=88,90,92)
    52.3
    53.3
    46.7
        Week 180 (n=88,90,92)
    51.1
    54.4
    46.7
        Week 192 (n=88,90,92)
    51.1
    55.6
    46.7
        Week 204 (n=88,90,92)
    50
    54.4
    46.7
        Week 216 (n=88,90,92)
    50
    54.4
    46.7
    Notes
    [2] - All participants with evaluable data at given time point.
    [3] - All participants with evaluable data at given time point.
    [4] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Percentage of Participants in the PBO/EW/EW Analysis Population Achieving Clinical Response Per HiSCR at Each Visit

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    End point title
    Percentage of Participants in the PBO/EW/EW Analysis Population Achieving Clinical Response Per HiSCR at Each Visit [5]
    End point description
    Clinical response per HiSCR defined as percent reduction from baseline of the prior phase 3 study in the abscess and inflammatory nodule ≥ 50% (AN50) with no increase in the abscess count and no increase in the draining fistula count. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of Period B in prior phase 3 study, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and 204
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    PBO/EW/EW
    Number of subjects analysed
    115 [6]
    Units: percentage of participants
    number (not applicable)
        Entry of Period B (n=115)
    26.1
        Week 12 (n=114)
    54.4
        Week 24 (n=114)
    57.9
        Week 36 (n=114)
    57
        Week 48 (n=114)
    60.5
        Week 60 (n=114)
    57
        Week 72 (n=114)
    50
        Week 84 (n=114)
    50
        Week 96 (n=114)
    53.5
        Week 108 (n=114)
    52.6
        Week 120 (n=114)
    53.5
        Week 132 (n=114)
    56.1
        Week 144 (n=114)
    51.8
        Week 156 (n=114)
    52.6
        Week 168 (n=114)
    55.3
        Week 180 (n=114)
    54.4
        Week 192 (n=114)
    53.5
        Week 204 (n=114)
    53.5
    Notes
    [6] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Percentage of Participants in the PBO/PBO/EW Analysis Population Achieving Clinical Response Per HiSCR at Each Visit

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    End point title
    Percentage of Participants in the PBO/PBO/EW Analysis Population Achieving Clinical Response Per HiSCR at Each Visit [7]
    End point description
    Clinical response per HiSCR defined as percent reduction from baseline of the prior phase 3 study in the abscess and inflammatory nodule ≥ 50% (AN50) with no increase in the abscess count and no increase in the draining fistula count. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of M12-555, Weeks 4, 8, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    PBO/PBO/EW
    Number of subjects analysed
    123 [8]
    Units: percentage of participants
    number (not applicable)
        Entry of M12-555 (n=123)
    19.5
        Week 4 (n=122)
    46.7
        Week 8 (n=122)
    51.6
        Week 12 (n=122)
    48.4
        Week 18 (n=122)
    57.4
        Week 24 (n=122)
    55.7
        Week 36 (n=122)
    60.7
        Week 48 (n=122)
    54.9
        Week 60 (n=122)
    55.7
        Week 72 (n=122)
    54.9
        Week 84 (n=122)
    54.9
        Week 96 (n=122)
    57.4
        Week 108 (n=122)
    54.9
        Week 120 (n=122)
    52.5
        Week 132 (n=122)
    54.1
        Week 144 (n=122)
    51.6
        Week 156 (n=122)
    50.8
        Week 168 (n=122)
    51.6
        Week 180 (n=122)
    51.6
        Week 192 (n=122)
    51.6
    Notes
    [8] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Percentage of Participants in the EW/EW/EW Analysis Population Who Achieved Abscess and Inflammatory Nodule (AN) Count of 0, 1, or 2 at Each Visit

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    End point title
    Percentage of Participants in the EW/EW/EW Analysis Population Who Achieved Abscess and Inflammatory Nodule (AN) Count of 0, 1, or 2 at Each Visit [9]
    End point description
    The percentage of participants with AN counts lowered to 0, 1, or 2 at each visit. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits.
    End point type
    Primary
    End point timeframe
    Weeks 2 (first dose of adalimumab in prior phase 3 study), 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EW/EW
    Number of subjects analysed
    88 [10]
    Units: percentage of participants
    number (not applicable)
        Week 2
    22.7
        Week 4
    28.4
        Week 8
    38.6
        Week 12
    35.2
        Week 16
    37.5
        Week 20
    42
        Week 24
    36.4
        Week 36
    48.9
        Week 48
    46.6
        Week 60
    43.2
        Week 72
    50
        Week 84
    45.5
        Week 96
    44.3
        Week 108
    46.6
        Week 120
    44.3
        Week 132
    44.3
        Week 144
    43.2
        Week 156
    45.5
        Week 168
    46.6
        Week 180
    46.6
        Week 192
    47.7
        Week 204
    47.7
        Week 216
    46.6
    Notes
    [10] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Percentage of Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations Who Achieved AN Count of 0, 1, or 2 at Each Visit

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    End point title
    Percentage of Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations Who Achieved AN Count of 0, 1, or 2 at Each Visit [11]
    End point description
    The percentage of participants with AN counts lowered to 0, 1, or 2 at each visit. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of M12-555, Weeks 4, 8, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EOW/EW EW/PBO/EW PBO/PBO/EW
    Number of subjects analysed
    90 [12]
    92 [13]
    123 [14]
    Units: percentage of participants
    number (not applicable)
        Entry of M12-555 (n=90,92,123)
    31.1
    22.8
    21.1
        Week 4 (n=87,92,122)
    35.6
    34.8
    44.3
        Week 8 (n=88,92,122)
    43.2
    42.4
    53.3
        Week 12 (n=88,92,122)
    45.5
    44.6
    45.1
        Week 18 (n=88,92,122)
    50
    41.3
    50
        Week 24 (n=88,92,122)
    43.2
    46.7
    57.4
        Week 36 (n=88,92,122)
    54.5
    45.7
    57.4
        Week 48 (n=88,92,122)
    50
    42.4
    52.5
        Week 60 (n=88,92,122)
    48.9
    43.5
    51.6
        Week 72 (n=88,92,122)
    50
    43.5
    54.1
        Week 84 (n=88,92,122)
    53.4
    44.6
    50.8
        Week 96 (n=88,92,122)
    51.1
    40.2
    52.5
        Week 108 (n=88,92,122)
    51.1
    40.2
    51.6
        Week 120 (n=88,92,122)
    46.6
    37
    52.5
        Week 132 (n=88,92,122)
    51.1
    37
    53.3
        Week 144 (n=88,92,122)
    48.9
    41.3
    52.5
        Week 156 (n=88,92,122)
    47.7
    39.1
    51.6
        Week 168 (n=88,92,122)
    51.1
    35.9
    51.6
        Week 180 (n=88,92,122)
    51.1
    35.9
    51.6
        Week 192 (n=88,92,122)
    51.1
    35.9
    51.6
    Notes
    [12] - All participants with evaluable data at given time point.
    [13] - All participants with evaluable data at given time point.
    [14] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Percentage of Participants in the PBO/EW/EW Analysis Population Who Achieved AN Count of 0, 1, or 2 at Each Visit

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    End point title
    Percentage of Participants in the PBO/EW/EW Analysis Population Who Achieved AN Count of 0, 1, or 2 at Each Visit [15]
    End point description
    The percentage of participants with AN counts lowered to 0, 1, or 2 at each visit. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of Period B in prior phase 3 study, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and 204
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    PBO/EW/EW
    Number of subjects analysed
    115 [16]
    Units: percentage of participants
    number (not applicable)
        Entry of Period B (n=115)
    20
        Week 12 (n=114)
    38.6
        Week 24 (n=114)
    43
        Week 36 (n=114)
    42.1
        Week 48 (n=114)
    43.9
        Week 60 (n=114)
    45.6
        Week 72 (n=114)
    43.9
        Week 84 (n=114)
    43.9
        Week 96 (n=114)
    46.5
        Week 108 (n=114)
    42.1
        Week 120 (n=114)
    45.6
        Week 132 (n=114)
    46.5
        Week 144 (n=114)
    49.1
        Week 156 (n=114)
    45.6
        Week 168 (n=114)
    46.5
        Week 180 (n=114)
    46.5
        Week 192 (n=114)
    45.6
        Week 204 (n=114)
    45.6
    Notes
    [16] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Modified Sartorius Score: Change From Baseline to Each Visit for Participants in the EW/EW/EW Analysis Population

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    End point title
    Modified Sartorius Score: Change From Baseline to Each Visit for Participants in the EW/EW/EW Analysis Population [17]
    End point description
    The Sartorius Scale is used to quantify the severity of HS. Points are awarded for 12 body areas (left and right axillae, left and right sub/inframammary areas, intermammary area, left and right buttocks, left and right inguino-crural folds, perianal area, perineal area, and other): points were awarded for nodules (2 points for each); abscesses (4 points); fistulas (4 points); scars (1 point); other findings (1 point); and longest distance between two lesions (2-6 points, 0 if no lesions); and if lesions are separated by normal skin (yes-0 points; no-6 points). The total Sartorius score is the sum of the 12 regional scores. Higher scores indicate greater severity of HS. A negative change indicates decrease in severity. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits.
    End point type
    Primary
    End point timeframe
    Baseline (in prior phase 3 study) to Weeks 2 (first dose of adalimumab in prior phase 3 study), 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EW/EW
    Number of subjects analysed
    88 [18]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Week 2
    -18 ± 25.27
        Week 4
    -21 ± 31.81
        Week 8
    -22.8 ± 35.45
        Week 12
    -23.9 ± 48.3
        Week 16
    -26.6 ± 54.63
        Week 20
    -32.1 ± 73.69
        Week 24
    -36.6 ± 74.99
        Week 36
    -41.6 ± 93.11
        Week 48
    -42.2 ± 115.22
        Week 60
    -41.9 ± 119.98
        Week 72
    -43.2 ± 122.3
        Week 84
    -42.8 ± 123.18
        Week 96
    -43.2 ± 126.21
        Week 108
    -43.2 ± 124.92
        Week 120
    -43.4 ± 127.65
        Week 132
    -42.5 ± 128.45
        Week 144
    -42.4 ± 129.37
        Week 156
    -40.7 ± 130.3
        Week 168
    -41.5 ± 130.4
        Week 180
    -41.8 ± 129.89
        Week 192
    -41.9 ± 130.46
        Week 204
    -41.4 ± 130.72
        Week 216
    -41.4 ± 130.94
    Notes
    [18] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Modified Sartorius Score: Change From Baseline to Each Visit for Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations

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    End point title
    Modified Sartorius Score: Change From Baseline to Each Visit for Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations [19]
    End point description
    The Sartorius Scale is used to quantify the severity of HS. Points are awarded for 12 body areas (left and right axillae, left and right sub/inframammary areas, intermammary area, left and right buttocks, left and right inguino-crural folds, perianal area, perineal area, and other): points were awarded for nodules (2 points for each); abscesses (4 points); fistulas (4 points); scars (1 point); other findings (1 point); and longest distance between two lesions (2-6 points, 0 if no lesions); and if lesions are separated by normal skin (yes-0 points; no-6 points). The total Sartorius score is the sum of the 12 regional scores. Higher scores indicate greater severity of HS. A negative change indicates decrease in severity. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Baseline (in prior phase 3 study) to Entry of M12-555 and Weeks 4, 8, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EOW/EW EW/PBO/EW PBO/PBO/EW
    Number of subjects analysed
    90 [20]
    92 [21]
    123 [22]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Entry of M12-555 (n=90,92,123)
    -23.1 ± 56.94
    -10.5 ± 56.74
    0.2 ± 51.35
        Week 4 (n=87,92,122)
    -30.2 ± 48.99
    -18.8 ± 56.52
    -16.2 ± 56.16
        Week 8 (n=88,92,122)
    -34.9 ± 47.42
    -21.2 ± 63.26
    -24.8 ± 51.55
        Week 12 (n=88,92,122)
    -34.8 ± 55.71
    -25.5 ± 57.92
    -26.2 ± 54.58
        Week 18 (n=88,92,122)
    -35.9 ± 47.92
    -26.2 ± 60.59
    -32.3 ± 48.6
        Week 24 (n=88,92,122)
    -37.1 ± 47.39
    -24.1 ± 61.52
    -33.5 ± 50.2
        Week 36 (n=88,92,122)
    -37.1 ± 46.07
    -24.7 ± 63.81
    -33.6 ± 57.58
        Week 48 (n=88,92,122)
    -37.5 ± 47.94
    -24.8 ± 63.21
    -30.2 ± 64.84
        Week 60 (n=88,92,122)
    -34.8 ± 50.17
    -22.6 ± 65.06
    -31.7 ± 66.33
        Week 72 (n=88,92,122)
    -35.4 ± 55.22
    -20.1 ± 64.52
    -31.8 ± 65.26
        Week 84 (n=88,92,122)
    -36.6 ± 51.33
    -20 ± 66.02
    -29.5 ± 65.79
        Week 96 (n=88,92,122)
    -34 ± 49.42
    -18.3 ± 65.14
    -29 ± 68.85
        Week 108 (n=88,92,122)
    -34 ± 54.41
    -18.3 ± 66.88
    -28.4 ± 71.52
        Week 120 (n=88,92,122)
    -31.8 ± 60.85
    -16.2 ± 66.82
    -28.3 ± 70.37
        Week 132 (n=88,92,122)
    -35.1 ± 53.01
    -16.7 ± 66.87
    -28.8 ± 69.79
        Week 144 (n=88,92,122)
    -35.1 ± 53.94
    -16.6 ± 67.3
    -28.6 ± 70.03
        Week 156 (n=88,92,122)
    -34.7 ± 53.95
    -15.7 ± 67.09
    -28 ± 69.11
        Week 168 (n=88,92,122)
    -35.6 ± 53.72
    -15.5 ± 67.4
    -28.7 ± 69.81
        Week 180 (n=88,92,122)
    -35.6 ± 53.64
    -15.4 ± 67.39
    -28.7 ± 69.81
        Week 192 (n=88,92,122)
    -35.6 ± 53.64
    -15.4 ± 67.39
    -28.7 ± 69.81
    Notes
    [20] - All participants with evaluable data at given time point.
    [21] - All participants with evaluable data at given time point.
    [22] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Modified Sartorius Score: Change From Baseline to Each Visit for Participants in the PBO/EW/EW Analysis Population

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    End point title
    Modified Sartorius Score: Change From Baseline to Each Visit for Participants in the PBO/EW/EW Analysis Population [23]
    End point description
    The Sartorius Scale is used to quantify the severity of HS. Points are awarded for 12 body areas (left and right axillae, left and right sub/inframammary areas, intermammary area, left and right buttocks, left and right inguino-crural folds, perianal area, perineal area, and other): points were awarded for nodules (2 points for each); abscesses (4 points); fistulas (4 points); scars (1 point); other findings (1 point); and longest distance between two lesions (2-6 points, 0 if no lesions); and if lesions are separated by normal skin (yes-0 points; no-6 points). The total Sartorius score is the sum of the 12 regional scores. Higher scores indicate greater severity of HS. A negative change indicates decrease in severity. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Baseline (in prior phase 3 study) to Entry of Period B in prior phase 3 study and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and 204
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    PBO/EW/EW
    Number of subjects analysed
    115 [24]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Entry of Period B (n=115)
    -18 ± 38.32
        Week 12 (n=114)
    -43.2 ± 48.07
        Week 24 (n=114)
    -43 ± 53.08
        Week 36 (n=114)
    -49.5 ± 57.05
        Week 48 (n=114)
    -47.1 ± 61.95
        Week 60 (n=114)
    -46.2 ± 60.94
        Week 72 (n=114)
    -44.5 ± 67.13
        Week 84 (n=114)
    -46.8 ± 64.57
        Week 96 (n=114)
    -45.5 ± 70.63
        Week 108 (n=114)
    -45 ± 74.15
        Week 120 (n=114)
    -45.9 ± 75.3
        Week 132 (n=114)
    -44.4 ± 78.09
        Week 144 (n=114)
    -45.4 ± 76.53
        Week 156 (n=114)
    -46 ± 76.17
        Week 168 (n=114)
    -46.1 ± 75.84
        Week 180 (n=114)
    -45.8 ± 75.96
        Week 192 (n=114)
    -45.8 ± 75.89
        Week 204 (n=114)
    -45.9 ± 75.96
    Notes
    [24] - All participants with evaluable data at given time point.
    No statistical analyses for this end point

    Primary: Percentage of Participants in the EW/EW/EW Analysis Population Achieving Skin Pain NRS30 - At Worst at Each Visit Among Participants With Baseline Skin Pain NRS At Worst ≥ 3

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    End point title
    Percentage of Participants in the EW/EW/EW Analysis Population Achieving Skin Pain NRS30 - At Worst at Each Visit Among Participants With Baseline Skin Pain NRS At Worst ≥ 3 [25]
    End point description
    The Patient's Global Assessment of Skin Pain Numeric Rating Scale (NRS) was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the "last 24 hours." The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the Patient's Global Assessment of Skin Pain (NRS30) - at worst at each visit among participants with baseline skin pain NRS - at worst ≥ 3 are presented. Weekly averages of daily assessments were analyzed. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits.
    End point type
    Primary
    End point timeframe
    Weeks 2 (first dose of adalimumab in prior phase 3 study), 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EW/EW
    Number of subjects analysed
    63 [26]
    Units: percentage of participants
    number (not applicable)
        Week 2
    47.6
        Week 4
    46
        Week 8
    44.4
        Week 12
    42.9
        Week 16
    46
        Week 20
    50.8
        Week 24
    54
        Week 36
    58.7
        Week 48
    54
        Week 60
    52.4
        Week 72
    54
        Week 84
    52.4
        Week 96
    49.2
        Week 108
    54
        Week 120
    50.8
        Week 132
    46
        Week 144
    54
        Week 156
    52.4
        Week 168
    52.4
        Week 180
    52.4
        Week 192
    52.4
    Notes
    [26] - All participants with baseline skin pain NRS-at worst ≥3 and with evaluable data at given time point
    No statistical analyses for this end point

    Primary: Percentage of Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations Achieving Skin Pain NRS30 - At Worst at Each Visit Among Participants With Baseline Skin Pain NRS At Worst ≥ 3

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    End point title
    Percentage of Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations Achieving Skin Pain NRS30 - At Worst at Each Visit Among Participants With Baseline Skin Pain NRS At Worst ≥ 3 [27]
    End point description
    The NRS was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the "last 24 hours." The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the NRS (NRS30) - at worst at each visit among participants with baseline skin pain NRS - at worst ≥ 3 are presented. Weekly averages of daily assessments were analyzed. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of M12-555, and Weeks 4, 8, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192
    Notes
    [27] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EOW/EW EW/PBO/EW PBO/PBO/EW
    Number of subjects analysed
    65 [28]
    64 [29]
    84 [30]
    Units: percentage of participants
    number (not applicable)
        Entry of M12-555 (n=65,64,84)
    40
    21.9
    22.6
        Week 4 (n=61,58,83)
    47.5
    43.1
    44.6
        Week 8 (n=62,63,83)
    45.2
    47.6
    51.8
        Week 12 (n=63,63,83)
    41.3
    54
    51.8
        Week 18 (n=63,63,83)
    47.6
    50.8
    55.4
        Week 24 (n=63,63,83)
    42.9
    47.6
    54.2
        Week 36 (n=63,63,83)
    49.2
    47.6
    55.4
        Week 48 (n=63,63,83)
    47.6
    50.8
    56.6
        Week 60 (n=63,63,83)
    47.6
    50.8
    50.6
        Week 72 (n=63,63,83)
    47.6
    42.9
    50.6
        Week 84 (n=63,63,83)
    50.8
    46
    48.2
        Week 96 (n=63,63,83)
    50.8
    55.6
    48.2
        Week 108 (n=63,63,83)
    50.8
    42.9
    50.6
        Week 120 (n=63,63,83)
    42.9
    47.6
    45.8
        Week 132 (n=63,63,83)
    41.3
    47.6
    48.2
        Week 144 (n=63,63,83)
    41.3
    50.8
    47
        Week 156 (n=63,63,83)
    39.7
    46
    49.4
        Week 168 (n=63,63,83)
    41.3
    49.2
    48.2
        Week 180 (n=63,63,83)
    41.3
    49.2
    48.2
        Week 192 (n=63,63,83)
    41.3
    49.2
    48.2
    Notes
    [28] - All participants with baseline skin pain NRS-at worst ≥3 and with evaluable data at given time point
    [29] - All participants with baseline skin pain NRS-at worst ≥3 and with evaluable data at given time point
    [30] - All participants with baseline skin pain NRS-at worst ≥3 and with evaluable data at given time point
    No statistical analyses for this end point

    Primary: Percentage of Participants in the PBO/EW/EW Analysis Population Achieving Skin Pain NRS30 - At Worst at Each Visit Among Participants With Baseline Skin Pain NRS At Worst ≥ 3

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    End point title
    Percentage of Participants in the PBO/EW/EW Analysis Population Achieving Skin Pain NRS30 - At Worst at Each Visit Among Participants With Baseline Skin Pain NRS At Worst ≥ 3 [31]
    End point description
    The NRS was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the "last 24 hours." The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the NRS (NRS30) - at worst at each visit among participants with baseline skin pain NRS - at worst ≥ 3 are presented. Weekly averages of daily assessments were analyzed. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of Period B in prior phase 3 study, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and 204
    Notes
    [31] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    PBO/EW/EW
    Number of subjects analysed
    79 [32]
    Units: percentage of participants
    number (not applicable)
        Entry of Period B (n=79)
    31.6
        Week 12 (n=64)
    51.6
        Week 24 (n=76)
    55.3
        Week 36 (n=77)
    55.8
        Week 48 (n=77)
    53.2
        Week 60 (n=77)
    58.4
        Week 72 (n=77)
    64.9
        Week 84 (n=77)
    63.6
        Week 96 (n=77)
    62.3
        Week 108 (n=78)
    55.1
        Week 120 (n=78)
    56.4
        Week 132 (n=78)
    53.8
        Week 144 (n=78)
    55.1
        Week 156 (n=78)
    51.3
        Week 168 (n=78)
    57.7
        Week 180 (n=78)
    57.7
        Week 192 (n=78)
    56.4
        Week 204 (n=78)
    57.7
    Notes
    [32] - All participants with baseline skin pain NRS-at worst ≥3 and with evaluable data at given time point
    No statistical analyses for this end point

    Primary: Percentage of Participants in the EW/EW/EW Analysis Population Achieving Skin Pain NRS30 - On Average at Each Visit Among Participants With Baseline Skin Pain NRS On Average ≥ 3

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    End point title
    Percentage of Participants in the EW/EW/EW Analysis Population Achieving Skin Pain NRS30 - On Average at Each Visit Among Participants With Baseline Skin Pain NRS On Average ≥ 3 [33]
    End point description
    The NRS was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the "last 24 hours." The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the NRS (NRS30) - on average at each visit among participants with baseline skin pain NRS - on average ≥ 3 are presented. Weekly averages of daily assessments were analyzed. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits.
    End point type
    Primary
    End point timeframe
    Weeks 2 (first dose of adalimumab in prior phase 3 study), 4, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192
    Notes
    [33] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EW/EW
    Number of subjects analysed
    50 [34]
    Units: percentage of participants
    number (not applicable)
        Week 2
    56
        Week 4
    52
        Week 8
    48
        Week 12
    46
        Week 16
    40
        Week 20
    50
        Week 24
    46
        Week 36
    58
        Week 48
    56
        Week 60
    56
        Week 72
    56
        Week 84
    56
        Week 96
    54
        Week 108
    50
        Week 120
    48
        Week 132
    56
        Week 144
    56
        Week 156
    58
        Week 168
    56
        Week 180
    56
        Week 192
    56
    Notes
    [34] - All participants with baseline skin pain NRS-on average ≥3 with evaluable data at given time point
    No statistical analyses for this end point

    Primary: Percentage of Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations Achieving Skin Pain NRS30 - On Average at Each Visit Among Participants With Baseline Skin Pain NRS On Average ≥ 3

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    End point title
    Percentage of Participants in the EW/EOW/EW, EW/PBO/EW, and PBO/PBO/EW Analysis Populations Achieving Skin Pain NRS30 - On Average at Each Visit Among Participants With Baseline Skin Pain NRS On Average ≥ 3 [35]
    End point description
    The NRS was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the "last 24 hours." The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the NRS (NRS30) - on average at each visit among participants with baseline skin pain NRS - on average ≥ 3 are presented. Weekly averages of daily assessments were analyzed. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of M12-555, and Weeks 4, 8, 12, 18, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192
    Notes
    [35] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    EW/EOW/EW EW/PBO/EW PBO/PBO/EW
    Number of subjects analysed
    55 [36]
    53 [37]
    69 [38]
    Units: percentage of participants
    number (not applicable)
        Entry of M12-555 (n=55,53,69)
    43.6
    37.7
    31.9
        Week 4 (n=51,47,68)
    49
    46.8
    61.8
        Week 8 (n=52,52,68)
    46.2
    55.8
    61.8
        Week 12 (n=53,52,68)
    39.6
    59.6
    58.8
        Week 18 (n=53,52,68)
    45.3
    59.6
    63.2
        Week 24 (n=53,52,68)
    39.6
    53.8
    54.4
        Week 36 (n=53,52,68)
    45.3
    48.1
    58.8
        Week 48 (n=53,52,68)
    47.2
    51.9
    58.8
        Week 60 (n=53,52,68)
    43.4
    53.8
    55.9
        Week 72 (n=53,52,68)
    47.2
    59.6
    55.9
        Week 84 (n=53,52,68)
    49.1
    48.1
    52.9
        Week 96 (n=53,52,68)
    47.2
    57.7
    57.4
        Week 108 (n=53,52,68)
    49.1
    44.2
    54.4
        Week 120 (n=53,52,68)
    39.6
    48.1
    54.4
        Week 132 (n=53,52,68)
    43.4
    50
    54.4
        Week 144 (n=53,52,68)
    43.4
    50
    54.4
        Week 156 (n=53,52,68)
    43.4
    46.2
    55.9
        Week 168 (n=53,52,68)
    43.4
    48.1
    54.4
        Week 180 (n=53,52,68)
    43.4
    48.1
    54.4
        Week 192 (n=53,52,68)
    43.4
    48.1
    54.4
    Notes
    [36] - All participants with baseline skin pain NRS-on average ≥3 with evaluable data at given time point
    [37] - All participants with baseline skin pain NRS-on average ≥3 with evaluable data at given time point
    [38] - All participants with baseline skin pain NRS-on average ≥3 with evaluable data at given time point
    No statistical analyses for this end point

    Primary: Percentage of Participants in the PBO/EW/EW Analysis Population Achieving Skin Pain NRS30 - On Average at Each Visit Among Participants With Baseline Skin Pain NRS On Average ≥ 3

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    End point title
    Percentage of Participants in the PBO/EW/EW Analysis Population Achieving Skin Pain NRS30 - On Average at Each Visit Among Participants With Baseline Skin Pain NRS On Average ≥ 3 [39]
    End point description
    The NRS was used to assess the worst skin pain and the average skin pain due to HS. Ratings for the 2 items range from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). The assessments were completed on a daily diary by participants before they went to bed and responded to the items based on a recall period of the "last 24 hours." The percentage of participants who achieved at least 30% reduction and at least 1 unit reduction from Baseline in the NRS (NRS30) - on average at each visit among participants with baseline skin pain NRS - on average ≥ 3 are presented. Weekly averages of daily assessments were analyzed. LOCF: The last completed evaluation from the previous visit was carried forward to impute missing data at later visits. n=number of participants at given time point.
    End point type
    Primary
    End point timeframe
    Entry of Period B in prior phase 3 study, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, and 204
    Notes
    [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive data were summarized for this endpoint per protocol.
    End point values
    PBO/EW/EW
    Number of subjects analysed
    62 [40]
    Units: percentage of participants
    number (not applicable)
        Entry of Period B (n=62)
    30.6
        Week 12 (n=49)
    59.2
        Week 24 (n=59)
    61
        Week 36 (n=60)
    61.7
        Week 48 (n=60)
    53.3
        Week 60 (n=60)
    60
        Week 72 (n=60)
    58.3
        Week 84 (n=60)
    60
        Week 96 (n=60)
    61.7
        Week 108 (n=61)
    62.3
        Week 120 (n=61)
    62.3
        Week 132 (n=61)
    59
        Week 144 (n=61)
    60.7
        Week 156 (n=61)
    55.7
        Week 168 (n=61)
    62.3
        Week 180 (n=61)
    62.3
        Week 192 (n=61)
    60.7
        Week 204 (n=61)
    62.3
    Notes
    [40] - All participants with baseline skin pain NRS-on average ≥3 with evaluable data at given time point
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug (up to 225 weeks).
    Adverse event reporting additional description
    TEAEs and TESAEs were defined as AEs and SAEs with an onset date on or after the first dose of adalimumab in either M12-555 or in prior studies M11-313 or M11-810, excluding AEs and SAEs with onset date during a protocol-defined treatment gap.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    All Adalimumab
    Reporting group description
    Participants who received at least 1 dose of adalimumab (40 mg every week) in M12-555.

    Serious adverse events
    All Adalimumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    99 / 508 (19.49%)
         number of deaths (all causes)
    3
         number of deaths resulting from adverse events
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypertension
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer stage III
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac myxoma
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hodgkin's disease
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Metastases to liver
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Papillary cystadenoma lymphomatosum
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Seminoma
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Social circumstances
    Sexual abuse
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Suicidal ideation
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pelvic prolapse
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Uterine cyst
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysfunctional uterine bleeding
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ankle fracture
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Burns second degree
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Contusion
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Joint injury
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Meniscus injury
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural dizziness
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural nausea
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Procedural pain
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Radial head dislocation
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Scar
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Autoantibody positive
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Body temperature increased
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Palpitations
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Congenital, familial and genetic disorders
    Odontogenic cyst
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coma hepatic
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Hemiplegia
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Autoimmune pancreatitis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Crohn's disease
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Incarcerated umbilical hernia
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritoneal cyst
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Ureteric obstruction
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Cutis laxa
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hidradenitis
         subjects affected / exposed
    29 / 508 (5.71%)
         occurrences causally related to treatment / all
    1 / 39
         deaths causally related to treatment / all
    0 / 0
    Pustular psoriasis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pyoderma gangrenosum
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Dermatitis contact
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Joint instability
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Muscle spasms
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Obesity
         subjects affected / exposed
    3 / 508 (0.59%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infection
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritonitis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Periumbilical abscess
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 508 (0.59%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Pneumonia chlamydial
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    2 / 508 (0.39%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Vulval abscess
         subjects affected / exposed
    1 / 508 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    All Adalimumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    349 / 508 (68.70%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    28 / 508 (5.51%)
         occurrences all number
    31
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    27 / 508 (5.31%)
         occurrences all number
    31
    Nervous system disorders
    Headache
         subjects affected / exposed
    80 / 508 (15.75%)
         occurrences all number
    149
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    29 / 508 (5.71%)
         occurrences all number
    42
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    33 / 508 (6.50%)
         occurrences all number
    36
    Nausea
         subjects affected / exposed
    32 / 508 (6.30%)
         occurrences all number
    37
    Skin and subcutaneous tissue disorders
    Hidradenitis
         subjects affected / exposed
    125 / 508 (24.61%)
         occurrences all number
    237
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    38 / 508 (7.48%)
         occurrences all number
    44
    Back pain
         subjects affected / exposed
    33 / 508 (6.50%)
         occurrences all number
    41
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    37 / 508 (7.28%)
         occurrences all number
    48
    Gastroenteritis
         subjects affected / exposed
    26 / 508 (5.12%)
         occurrences all number
    33
    Influenza
         subjects affected / exposed
    40 / 508 (7.87%)
         occurrences all number
    58
    Nasopharyngitis
         subjects affected / exposed
    92 / 508 (18.11%)
         occurrences all number
    172
    Sinusitis
         subjects affected / exposed
    29 / 508 (5.71%)
         occurrences all number
    43
    Upper respiratory tract infection
         subjects affected / exposed
    84 / 508 (16.54%)
         occurrences all number
    140
    Urinary tract infection
         subjects affected / exposed
    40 / 508 (7.87%)
         occurrences all number
    49

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Oct 2012
    The main purpose of this amendment was to add pharmacokinetic adalimumab concentration and anti-adalimumab antibody (AAA) assays to some study visits, and update phase 2 safety and efficacy information in the background section.
    07 Aug 2013
    The main purpose of this amendment was to add new safety monitoring language, incorporate new CDC guidelines on TB screening, add additional prohibited therapy (recently approved biologic therapies), add biomarker time points at weeks 12 and 48 visits, and add collection of information regarding surgery performed for chronic hidradenitis suppurativa (HS).

    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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