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    Clinical Trial Results:
    A Phase 2, randomized, double-blind, placebo-controlled, multiple ascending dose study to evaluate the efficacy and safety of CAM-3001 in participants with rheumatoid arthritis (RA).

    Summary
    EudraCT number
    2009-014735-20
    Trial protocol
    LV   EE   HU   CZ   LT   PL   BG  
    Global end of trial date
    27 Jul 2012

    Results information
    Results version number
    v1(current)
    This version publication date
    07 Jan 2017
    First version publication date
    07 Jan 2017
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MI-CP219
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01050998
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    MedImmune, LLC
    Sponsor organisation address
    Milstein Building, Granta Park, Cambridge, CB21 6GH United Kingdom, United Kingdom,
    Public contact
    Marius Albulescu, Associate Medical Director, MedImmune, LLC, +1 3013980000, albulescum@medimmune.com
    Scientific contact
    Marius Albulescu, Associate Medical Director, MedImmune, LLC, +1 3013980000, albulescum@medimmune.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
    27 Jul 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jul 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary objectives of this study were to evaluate the safety, tolerability, and efficacy of multiple doses of mavrilimumab administered subcutaneous (SC) in participants with at least moderately active rheumatoid arthritis (RA).
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Participating participant signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    11 Feb 2010
    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
    Bulgaria: 25
    Country: Number of subjects enrolled
    Czech Republic: 22
    Country: Number of subjects enrolled
    Estonia: 12
    Country: Number of subjects enrolled
    Japan: 51
    Country: Number of subjects enrolled
    Latvia: 9
    Country: Number of subjects enrolled
    Lithuania: 14
    Country: Number of subjects enrolled
    Poland: 29
    Country: Number of subjects enrolled
    Romania: 7
    Country: Number of subjects enrolled
    Russian Federation: 63
    Country: Number of subjects enrolled
    Ukraine: 28
    Country: Number of subjects enrolled
    Hungary: 24
    Worldwide total number of subjects
    284
    EEA total number of subjects
    142
    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)
    247
    From 65 to 84 years
    37
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 516 participants were screened out of which 290 participants were randomized in the study. Six participants from one of the sites were excluded from ITT population prior to unblinding due to data intergrity issues.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Mavrilimumab 10 milligram (mg)
    Arm description
    Participants received Mavrilimumab (CAM-3001) 10 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.
    Arm type
    Experimental

    Investigational medicinal product name
    Mavrilimumab
    Investigational medicinal product code
    CAM-3001
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Mavrilimumab (CAM-3001) 10 milligram (mg) injection subcutaneously every other week for 12 weeks.

    Arm title
    Mavrilimumab 30 mg
    Arm description
    Participants received Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.
    Arm type
    Experimental

    Investigational medicinal product name
    Mavrilimumab
    Investigational medicinal product code
    CAM-3001
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Mavrilimumab (CAM-3001) 30 milligram (mg) injection subcutaneously every other week for 12 weeks.

    Arm title
    Mavrilimumab 50 mg
    Arm description
    Participants received Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.
    Arm type
    Experimental

    Investigational medicinal product name
    Mavrilimumab
    Investigational medicinal product code
    CAM-3001
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks.

    Arm title
    Mavrilimumab 100 mg
    Arm description
    Participants received Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.
    Arm type
    Experimental

    Investigational medicinal product name
    Mavrilimumab
    Investigational medicinal product code
    CAM-3001
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks.

    Arm title
    Placebo
    Arm description
    Participants received Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants received Placebo Matched to Mavrilimumab injection subcutaneously every other week for 12 weeks.

    Number of subjects in period 1
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Started
    48
    49
    48
    47
    92
    Completed
    44
    47
    46
    45
    82
    Not completed
    4
    2
    2
    2
    10
         Adverse event, non-fatal
    1
    -
    1
    -
    2
         Consent withdrawn by subject
    -
    -
    -
    1
    3
         Unspecified
    3
    2
    1
    1
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Mavrilimumab 10 milligram (mg)
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 10 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Mavrilimumab 30 mg
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Mavrilimumab 50 mg
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Mavrilimumab 100 mg
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Placebo
    Reporting group description
    Participants received Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo Total
    Number of subjects
    48 49 48 47 92 284
    Age categorical
    Units: Subjects
        Adults (18- 64 Years)
    42 43 42 42 78 247
        Elderly (65-84 Years)
    6 6 6 5 14 37
    Age Continuous |
    Units: years
        arithmetic mean (standard deviation)
    52.2 ± 11.9 51.1 ± 12.1 52.7 ± 10.3 50.1 ± 12.1 52.1 ± 12.8 -
    Gender, Male/Female
    Units: participants
        Female
    39 43 44 40 82 248
        Male
    9 6 4 7 10 36

    End points

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    End points reporting groups
    Reporting group title
    Mavrilimumab 10 milligram (mg)
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 10 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Mavrilimumab 30 mg
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 30 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Mavrilimumab 50 mg
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Mavrilimumab 100 mg
    Reporting group description
    Participants received Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Reporting group title
    Placebo
    Reporting group description
    Participants received Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Subject analysis set title
    Placebo
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Placebo matched to mavrilimumab injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Subject analysis set title
    Mavrilimumab 50 mg
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received Mavrilimumab (CAM-3001) 50 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Subject analysis set title
    Mavrilimumab 100mg
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received Mavrilimumab (CAM-3001) 100 mg injection subcutaneously every other week for 12 weeks in combination with stable dose of methotrexate (7.5 to 25 mg per week) orally or parenterally.

    Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85

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    End point title
    Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85
    End point description
    DAS28 (CRP) calculated swollen joint count (SJC) and tender joint count (TJC) using the 28 joints, general health (GH) using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (milligram per Liter [mg/L]). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) less than (<) 3.2 = low disease activity, greater than or equal to (>=) 3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. The intent-to-treat (ITT) population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Primary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
        number (not applicable)
    37.5
    63.3
    47.9
    68.1
    32.6
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [1]
    P-value
    = 0.578 [2]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    4.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.5
         upper limit
    22
    Notes
    [1] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [2] - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [3]
    P-value
    < 0.001 [4]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    30.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    13.4
         upper limit
    46.3
    Notes
    [3] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [4] - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [5]
    P-value
    = 0.099 [6]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    15.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6
         upper limit
    32.2
    Notes
    [5] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [6] - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [7]
    P-value
    < 0.001 [8]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    35.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    17.8
         upper limit
    50.6
    Notes
    [7] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [8] - p-value was calculated using a two-tailed Fisher’s exact test.

    Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region

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    End point title
    Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using C-Reactive Protein (DAS28 [CRP]) Response at Day 85 by Region
    End point description
    DAS28 (CRP) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and CRP (mg/L). Total score range: 0-9.4, higher score= more disease activity. DAS28 (CRP) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (CRP) score at Day 85. DAS28 (CRP) response at Day 85 for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        European Region (n=75, 39, 41, 39, 39)
    41
    61
    51.3
    66.7
    34.7
        Japanese Region (n=17, 9, 8, 9, 8)
    22.2
    75
    33.3
    75
    23.5
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [9]
    P-value
    = 0.543 [10]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    6.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -11.9
         upper limit
    25.4
    Notes
    [9] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [10] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [11]
    P-value
    = 0.011 [12]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    26.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.2
         upper limit
    43.6
    Notes
    [11] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [12] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [13]
    P-value
    = 0.108 [14]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    16.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.5
         upper limit
    35.5
    Notes
    [13] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [14] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [15]
    P-value
    = 0.001 [16]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    12.5
         upper limit
    49
    Notes
    [15] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [16] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [17]
    P-value
    = 1 [18]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -33.7
         upper limit
    35.7
    Notes
    [17] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [18] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [19]
    P-value
    = 0.028 [20]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    51.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.2
         upper limit
    77
    Notes
    [19] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [20] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [21]
    P-value
    = 0.661 [22]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    9.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -24.3
         upper limit
    46.9
    Notes
    [21] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [22] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [23]
    P-value
    = 0.028 [24]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    51.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.2
         upper limit
    77
    Notes
    [23] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [24] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

    Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85

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    End point title
    Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85
    End point description
    DAS28 (ESR) calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst), and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score = more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Primary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
        number (not applicable)
    50
    61.2
    58.3
    66
    37
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [25]
    P-value
    = 0.152 [26]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.2
         upper limit
    30.3
    Notes
    [25] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [26] - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [27]
    P-value
    = 0.008 [28]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    24.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7
         upper limit
    40.3
    Notes
    [27] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [28] - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [29]
    P-value
    = 0.02 [30]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    21.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.9
         upper limit
    37.8
    Notes
    [29] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [30] - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [31]
    P-value
    = 0.002 [32]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    29
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    11.3
         upper limit
    45
    Notes
    [31] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [32] - p-value was calculated using a two-tailed Fisher’s exact test.

    Primary: Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region

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    End point title
    Percentage of Participants who Achieved Disease Activity Score of 28 Joints Using Erythrocyte Sedimentation Rate (DAS28 [ESR]) at Day 85 by Region
    End point description
    DAS28 (ESR) calculated SJC and TJC using the 28 joints,GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0=best, 10=worst),and the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]). Total score range: 0-9.4, higher score=more disease activity. DAS28 (ESR) <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. A Day 85 responder was defined as a participant who experienced more than 1.2 decrease from baseline in DAS28 (ESR) score at Day 85. DAS28 (ESR) response at Day 85 for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        European Region (n=75, 39, 41, 39, 39)
    51.3
    58.5
    61.5
    64.1
    41.3
        Japanese Region (n=17, 9, 8, 9, 8)
    44.4
    75
    44.4
    75
    17.6
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [33]
    P-value
    = 0.328 [34]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    9.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.3
         upper limit
    29.4
    Notes
    [33] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [34] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [35]
    P-value
    = 0.084 [36]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    17.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2
         upper limit
    35.6
    Notes
    [35] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [36] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [37]
    P-value
    = 0.049 [38]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    20.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.7
         upper limit
    38.2
    Notes
    [37] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [38] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [39]
    P-value
    = 0.03 [40]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    22.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.2
         upper limit
    40.7
    Notes
    [39] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [40] - European region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [41]
    P-value
    = 0.188 [42]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    26.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.3
         upper limit
    60.7
    Notes
    [41] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [42] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [43]
    P-value
    = 0.01 [44]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    57.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.2
         upper limit
    81.8
    Notes
    [43] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [44] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [45]
    P-value
    = 0.188 [46]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    26.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.3
         upper limit
    60.7
    Notes
    [45] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [46] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [47]
    P-value
    = 0.01 [48]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    57.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.2
         upper limit
    81.8
    Notes
    [47] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [48] - Japanese region: p-value was calculated using a two-tailed Fisher’s exact test.

    Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85

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    End point title
    Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 [49]
    End point description
    DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline more than (>)1.2 but less than (<) 3.2; moderate response: change from baseline >1.2 to more than or equal to (>=) 3.2 or less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 to >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 to >5.1. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [49] - 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 statistics were done, no inferential statistical analyses were performed.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        No response
    47.9
    28.6
    35.4
    23.4
    51.1
        Moderate response
    31.3
    38.8
    41.7
    42.6
    34.8
        Good response
    20.8
    32.7
    22.9
    34
    14.1
    No statistical analyses for this end point

    Primary: Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

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    End point title
    Percentage of Participants who Achieved DAS28 (CRP) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region [50]
    End point description
    DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline more than (>)1.2 but less than (<) 3.2; moderate response: change from baseline >1.2 to more than or equal to (>=) 3.2 or less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 to >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 to >5.1. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [50] - 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 statistics were done, no inferential statistical analyses were performed.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        European: No response (n=75,39,41,39,39)
    46.2
    29.3
    33.3
    23.1
    49.3
        European: Moderate response (n=75,39,41,39,39)
    33.3
    41.5
    41
    46.2
    36
        European: Good response (n=75,39,41,39,39)
    20.5
    29.3
    25.6
    30.8
    14.7
        Japanese: No response (n=17,9,8,9,8)
    55.6
    25
    44.4
    25
    58.8
        Japanese: Moderate response (n=17,9,8,9,8)
    22.2
    25
    44.4
    25
    29.4
        Japanese: Good response (n=17,9,8,9,8)
    22.2
    50
    11.1
    50
    11.8
    No statistical analyses for this end point

    Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85

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    End point title
    Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 [51]
    End point description
    DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline more than (>)1.2 but less than (<) 3.2; moderate response: change from baseline >1.2 to more than or equal to (>=) 3.2 or less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 to >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 to >5.1. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [51] - 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 statistics were done, no inferential statistical analyses were performed.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        No response
    39.6
    36.7
    33.3
    25.5
    55.4
        Moderate response
    45.8
    44.9
    54.2
    53.2
    35.9
        Good response
    14.6
    18.4
    12.5
    21.3
    8.7
    No statistical analyses for this end point

    Primary: Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region

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    End point title
    Percentage of Participants who Achieved DAS28 (ESR) Response by European League Against Rheumatism (EULAR) Category at Day 85 by Region [52]
    End point description
    DAS28 (CRP) response by EULAR category were used to measure individual response as none, moderate, and good, depending on the extent of change from baseline and the level of disease activity reached. Good response: change from baseline more than (>)1.2 but less than (<) 3.2; moderate response: change from baseline >1.2 to more than or equal to (>=) 3.2 or less than or equal to (=<) 5.1 or change from baseline >=0.6 to =< 1.2 to >=3.2 to =<5.1; no response: change from baseline <0.6 or change from baseline >=0.6 and =<1.2 to >5.1. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for the specified region for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [52] - 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 statistics were done, no inferential statistical analyses were performed.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        European: No response (n=75,39,41,39,39)
    38.5
    39
    33.3
    28.2
    53.3
        European: Moderate response (n=75,39,41,39,39)
    46.2
    43.9
    53.8
    51.3
    38.7
        European: Good response (n=75,39,41,39,39)
    15.4
    17.1
    12.8
    20.5
    8
        Japanese: No response (n=17,9,8,9,8)
    44.4
    25
    33.3
    12.5
    64.7
        Japanese: Moderate response (n=17,9,8,9,8)
    44.4
    50
    55.6
    62.5
    23.5
        Japanese: Good response (n=17,9,8,9,8)
    11.1
    25
    11.1
    25
    11.8
    No statistical analyses for this end point

    Primary: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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    End point title
    Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) [53] [54]
    End point description
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up Day 169 that were absent before treatment or that worsened relative to pretreatment state. The safety population included all participants who received any dose of investigational product.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 169 (follow-up)
    Notes
    [53] - 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 statistics were done, no inferential statistical analyses were performed.
    [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: participants
        TEAEs
    33
    31
    46
    26
    28
        TESAEs
    2
    2
    1
    1
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events (TEAEs) [55] [56]
    End point description
    Vital sign assessments included blood pressure, pulse rate, temperature, and respiration rate. Vital signs abnormalities reported as TEAEs were reported. The safety population included all participants who received any dose of investigational product.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 169 (follow-up)
    Notes
    [55] - 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 statistics were done, no inferential statistical analyses were performed.
    [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: participants
        Pyrexia
    0
    0
    1
    2
    0
        Hypertension
    0
    1
    2
    0
    0
    No statistical analyses for this end point

    Primary: Number of Participants With Abnormal Electrocardiogram (ECG) Results

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    End point title
    Number of Participants With Abnormal Electrocardiogram (ECG) Results [57] [58]
    End point description
    12-lead ECG was recorded and corrected QT (QTc) interval was measured with the participant in a rested supine position for at least 10 minutes. Any ECG abnormality deemed clinically significant as per investigator’s discretion were reported. The safety population included all participants who received any dose of investigational product.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 169 (follow-up)
    Notes
    [57] - 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 statistics were done, no inferential statistical analyses were performed.
    [58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: participants
    1
    0
    0
    0
    2
    No statistical analyses for this end point

    Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

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    End point title
    Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 [59] [60]
    End point description
    FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [59] - 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 statistics were done, no inferential statistical analyses were performed.
    [60] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    46
    47
    47
    87
    49
    Units: liters
    arithmetic mean (standard deviation)
        FEV1
    2.877 ± 0.821
    2.949 ± 0.722
    2.793 ± 0.69
    2.73 ± 0.764
    2.701 ± 0.489
        FVC
    3.582 ± 0.967
    3.667 ± 0.882
    3.499 ± 0.766
    3.439 ± 0.949
    3.37 ± 0.527
    No statistical analyses for this end point

    Primary: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region

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    End point title
    Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 by Region [61] [62]
    End point description
    FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FEV1 and FVC at Day 85 for the European and Japanese regions were reported. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for the specified region for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [61] - 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 statistics were done, no inferential statistical analyses were performed.
    [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    46
    47
    47
    87
    49
    Units: liters
    arithmetic mean (standard deviation)
        European: FEV1 (n=71,37,39,40,39)
    2.902 ± 0.81
    3.042 ± 0.745
    2.848 ± 0.699
    2.811 ± 0.79
    2.698 ± 0.501
        European: FVC (n=71,37,39,40,39)
    3.632 ± 0.948
    3.779 ± 0.917
    3.553 ± 0.772
    3.537 ± 0.996
    3.355 ± 0.537
        Japanese: FEV1 (n=16,9,8,9,8)
    2.774 ± 0.908
    2.493 ± 0.354
    2.52 ± 0.616
    2.367 ± 0.51
    2.712 ± 0.457
        Japanese: FVC (n=16,9,8,9,8)
    3.378 ± 1.076
    3.119 ± 0.37
    3.235 ± 0.725
    3.005 ± 0.534
    3.434 ± 0.505
    No statistical analyses for this end point

    Primary: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85

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    End point title
    Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) at Day 85 [63] [64]
    End point description
    FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Baseline and Day 85
    Notes
    [63] - 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 statistics were done, no inferential statistical analyses were performed.
    [64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: liters
    arithmetic mean (standard deviation)
        Baseline: FEV1 (n=87,43,45,49,48)
    2.788 ± 0.773
    2.99 ± 0.765
    2.79 ± 0.77
    2.76 ± 0.43
    2.831 ± 0.681
        Change at Day 85: FEV1 (n=87,46,47,49,47)
    0.044 ± 0.231
    0.016 ± 0.196
    -0.039 ± 0.234
    -0.059 ± 0.249
    -0.049 ± 0.221
        Baseline: FVC (n=87,43,45,49,48)
    3.486 ± 0.963
    3.759 ± 0.868
    3.456 ± 0.948
    3.409 ± 0.496
    3.506 ± 0.804
        Change at Day 85: FVC (n=87,46,47,49,47)
    0.048 ± 0.243
    -0.013 ± 0.239
    -0.012 ± 0.301
    -0.039 ± 0.496
    -0.017 ± 0.218
    No statistical analyses for this end point

    Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

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    End point title
    Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 [65] [66]
    End point description
    DLCO is a pulmonary function test that measures the partial pressure difference between inspired and expired carbon monoxide. The safety population included all participants who received any dose of investigational product. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [65] - 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 statistics were done, no inferential statistical analyses were performed.
    [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    46
    47
    47
    87
    49
    Units: percent diffusion capacity
        arithmetic mean (standard deviation)
    95 ± 16.2
    95 ± 15.1
    89.3 ± 12
    91.7 ± 16.7
    95 ± 15.7
    No statistical analyses for this end point

    Primary: Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region

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    End point title
    Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 by Region [67] [68]
    End point description
    DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% for the European and Japanese regions were reported. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [67] - 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 statistics were done, no inferential statistical analyses were performed.
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    46
    47
    47
    87
    49
    Units: percent diffusion capacity
    arithmetic mean (standard deviation)
        European region: (n=71,37,39,40,39)
    96 ± 16.9
    94 ± 15.2
    88.6 ± 10.7
    90.4 ± 16.5
    94.8 ± 16.5
        Japanese region (n=16,9,8,9,8)
    91 ± 13.3
    100.1 ± 14.6
    93 ± 17.2
    97.6 ± 16.9
    96 ± 12.6
    No statistical analyses for this end point

    Primary: Change from Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85

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    End point title
    Change from Baseline in Diffusing Capacity for Carbon Monoxide (DLCO) at Day 85 [69] [70]
    End point description
    DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Baseline and Day 85
    Notes
    [69] - 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 statistics were done, no inferential statistical analyses were performed.
    [70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: percent diffusion capacity
    arithmetic mean (standard deviation)
        Baseline (n=86,40,45,49,48)
    96.3 ± 17.7
    93.7 ± 15.5
    91.5 ± 12.5
    97.5 ± 14.8
    92.5 ± 13.7
        Change at Day 85 (n=87,46,47,49,47)
    -3.1 ± 17.3
    0.4 ± 11.1
    0.1 ± 14.3
    -2.5 ± 10.8
    -3.7 ± 11.3
    No statistical analyses for this end point

    Primary: Dyspnea Score at Day 85

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    End point title
    Dyspnea Score at Day 85 [71] [72]
    End point description
    Modified Borg dyspnea scale is a validated participant reported outcome assessing participant’s perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The safety population included all participants who received any dose of investigational product.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [71] - 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 statistics were done, no inferential statistical analyses were performed.
    [72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    45
    47
    47
    89
    49
    Units: units on a scale
        arithmetic mean (standard deviation)
    0.13 ± 0.38
    0.35 ± 0.7
    0.35 ± 0.59
    0.25 ± 0.48
    0.15 ± 0.44
    No statistical analyses for this end point

    Primary: Change from Baseline in Dyspnea Score at Day 85

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    End point title
    Change from Baseline in Dyspnea Score at Day 85 [73] [74]
    End point description
    Modified Borg dyspnea scale is a validated participant reported outcome assessing participant’s perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The safety population included all participants who received any dose of investigational product. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.
    End point type
    Primary
    End point timeframe
    Baseline and Day 85
    Notes
    [73] - 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 statistics were done, no inferential statistical analyses were performed.
    [74] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: units on a scale
    arithmetic mean (standard deviation)
        Baseline (n=96,48,49,49,48)
    0.26 ± 0.88
    0.26 ± 0.59
    0.29 ± 0.58
    0.19 ± 0.49
    0.32 ± 0.59
        Change at Day 85 (n=89,45,47,49,47)
    -0.14 ± 0.62
    0.1 ± 0.44
    -0.06 ± 0.53
    -0.04 ± 0.35
    0.02 ± 0.56
    No statistical analyses for this end point

    Primary: Categorized Dyspnea Score at Day 85

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    End point title
    Categorized Dyspnea Score at Day 85 [75] [76]
    End point description
    Modified Borg dyspnea scale is a validated participant reported outcome assessing participant’s perceived difficulty in breathing (dyspnea). The scale ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicate greater difficulty in breathing. The modified BORG dyspnea scale was categorized as - no/slight (0 to 2), moderate (3 and 4), severe (5 and 6) and very severe breathlessness (7 and above). The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [75] - 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 statistics were done, no inferential statistical analyses were performed.
    [76] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    45
    47
    47
    89
    49
    Units: participants
        No/Slight breathlessness
    45
    45
    46
    89
    49
        Moderate breathlessness
    0
    2
    1
    0
    0
        Severe breathlessness
    0
    0
    0
    0
    0
        Very severe breathlessness
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Oxygen Saturation Level at Day 85

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    End point title
    Oxygen Saturation Level at Day 85 [77] [78]
    End point description
    Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. The safety population included all participants who received any dose of investigational product. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [77] - 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 statistics were done, no inferential statistical analyses were performed.
    [78] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    45
    47
    47
    88
    49
    Units: percent saturation
        arithmetic mean (standard deviation)
    97.6 ± 1.3
    97.7 ± 1.3
    97.3 ± 1.5
    97.5 ± 1.2
    97.2 ± 1.8
    No statistical analyses for this end point

    Primary: Oxygen Saturation Level at Day 85 by Region

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    End point title
    Oxygen Saturation Level at Day 85 by Region [79] [80]
    End point description
    Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. Oxygen saturation for the European and Japanese regions were reported. The safety population included all participants who received any dose of investigational product. Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Day 85
    Notes
    [79] - 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 statistics were done, no inferential statistical analyses were performed.
    [80] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 100 mg Placebo Mavrilimumab 50 mg
    Number of subjects analysed
    45
    47
    47
    88
    49
    Units: percent saturation
    arithmetic mean (standard deviation)
        European region: (n=72,36,39,40,39)
    97.6 ± 1.3
    97.6 ± 1.3
    97.3 ± 1.6
    97.5 ± 1.3
    97.2 ± 2
        Japanese region: (n=16,9,8,9,8)
    97.4 ± 1
    98.4 ± 1.1
    97.3 ± 1.3
    97.6 ± 0.9
    97.4 ± 0.7
    No statistical analyses for this end point

    Primary: Change from Baseline in Oxygen Saturation Level at Day 85

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    End point title
    Change from Baseline in Oxygen Saturation Level at Day 85 [81] [82]
    End point description
    Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood. The safety population included all participants who received any dose of investigational product. Here "n" signifies participants who were evaluable for this measure at the specified time point for each arm, respectively.
    End point type
    Primary
    End point timeframe
    Baseline and Day 85
    Notes
    [81] - 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 statistics were done, no inferential statistical analyses were performed.
    [82] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: percent saturation
    arithmetic mean (standard deviation)
        Baseline (n=96,48,49,49,48)
    97.8 ± 1.6
    97.6 ± 1.2
    97.5 ± 1.3
    97.6 ± 1.4
    97.2 ± 1.7
        Change at Day 85 (n=88,45,47,49,47)
    -0.2 ± 1.5
    0.1 ± 1.4
    0 ± 1.5
    -0.3 ± 1.9
    0.1 ± 2.1
    No statistical analyses for this end point

    Primary: Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs)

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    End point title
    Number of Participants with Abnormal Clinical Laboratory Parameters Reported as Treatment-Emergent Adverse Events (TEAEs) [83] [84]
    End point description
    Any medically significant change in laboratory evaluations were recorded as adverse events. Following parameters were analyzed for laboratory examination: hematology (haemoglobin, reticulocytes, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration); serum chemistry (creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, gamma glutamyl transferase, CRP, ESR, albumin, total cholesterol, triglycerides, rheumatoid factor and anti-cyclic citrullinated peptide antibodies); urinalysis (albumin, glucose, protein, blood, nitrite). The safety population included all participants who received any dose of investigational product.
    End point type
    Primary
    End point timeframe
    Baseline up to Day 169 (follow-up)
    Notes
    [83] - 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 statistics were done, no inferential statistical analyses were performed.
    [84] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The subject analysis sets were created for the safety population due to difference in evaluable participants for the reporting groups and data has been represented accordingly; hence not all the baseline period arms included while reporting end point data.
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Placebo Mavrilimumab 50 mg Mavrilimumab 100mg
    Number of subjects analysed
    48
    49
    96
    49
    48
    Units: participants
        Blood and lymphatic system disorders
    3
    3
    10
    3
    4
        Hepatic abnormality
    5
    3
    3
    2
    3
        Blood cholesterol increased
    0
    0
    0
    1
    0
        Blood triglycerides increased
    0
    0
    1
    0
    0
        Hypercholesterolemia
    1
    1
    1
    1
    0
        Hyperglycemia
    0
    0
    1
    1
    0
        Urinalysis abnormalities
    0
    3
    3
    1
    0
    No statistical analyses for this end point

    Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85

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    End point title
    Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85
    End point description
    DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: units on a scale
    arithmetic mean (standard error)
        DAS28(CRP): Baseline (n=92,48,49,48,47)
    5.24 ± 0.16
    5.42 ± 0.139
    5.14 ± 0.146
    5.34 ± 0.115
    5.43 ± 0.11
        DAS28(CRP): Change at Day 85 (n=84,45,46,48,46)
    -1.27 ± 0.166
    -1.63 ± 0.163
    -1.32 ± 0.162
    -1.7 ± 0.165
    -0.97 ± 0.12
        DAS28(ESR): Baseline: (n=92,48,49,48,47)
    6.06 ± 0.165
    6.31 ± 0.145
    5.98 ± 0.163
    6.06 ± 0.119
    6.18 ± 0.118
        DAS28(ESR): Change at Day 85 (n=85,45,47,48,46)
    -1.39 ± 0.172
    -1.8 ± 0.17
    -1.46 ± 0.168
    -1.84 ± 0.172
    -1.04 ± 0.125
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [85]
    P-value
    = 0.137
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.31
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.71
         upper limit
    0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.205
    Notes
    [85] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [86]
    P-value
    = 0.001
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.67
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.07
         upper limit
    -0.27
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.202
    Notes
    [86] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [87]
    P-value
    = 0.08
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.35
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.75
         upper limit
    0.04
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.201
    Notes
    [87] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [88]
    P-value
    < 0.001
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.74
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.14
         upper limit
    -0.33
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.204
    Notes
    [88] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [89]
    P-value
    = 0.107
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.34
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.76
         upper limit
    0.08
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.212
    Notes
    [89] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [90]
    P-value
    < 0.001
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.76
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.17
         upper limit
    -0.35
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.21
    Notes
    [90] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [91]
    P-value
    = 0.046
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.42
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.83
         upper limit
    -0.01
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.209
    Notes
    [91] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [92]
    P-value
    < 0.001
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.22
         upper limit
    -0.38
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.212
    Notes
    [92] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

    Secondary: Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region

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    End point title
    Change from Baseline in DAS28 (CRP) and DAS28 (ESR) at Day 85 by Region
    End point description
    DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: units on a scale
    arithmetic mean (standard error)
        European: DAS28(CRP): Baseline (n=75,39,41,39,39)
    5.3 ± 0.172
    5.48 ± 0.154
    5.33 ± 0.155
    5.41 ± 0.111
    5.58 ± 0.117
        European: DAS28(CRP): Day 85 (n=68,36,38,39,38)
    -1.4 ± 0.187
    -1.55 ± 0.181
    -1.43 ± 0.181
    -1.7 ± 0.183
    -1 ± 0.133
        Japanese: DAS28(CRP): Baseline (n=17,9,8,9,8)
    5 ± 0.427
    5.12 ± 0.306
    4.32 ± 0.268
    5.04 ± 0.413
    4.75 ± 0.242
        Japanese: DAS28(CRP): Day 85 (n=16,9,8,9,8)
    -0.73 ± 0.358
    -2.04 ± 0.381
    -0.89 ± 0.361
    -1.71 ± 0.38
    -0.85 ± 0.281
        European: DAS28(ESR): Baseline (n=75,39,41,39,39)
    6.1 ± 0.18
    6.36 ± 0.163
    6.23 ± 0.159
    6.12 ± 0.118
    6.36 ± 0.124
        European: DAS28(ESR): Day 85 (n=69,36,39,39,38)
    -1.51 ± 0.196
    -1.76 ± 0.19
    -1.53 ± 0.19
    -1.85 ± 0.193
    -1.12 ± 0.14
        Japanese: DAS28(ESR): Baseline (n=17,9,8,9,8)
    5.87 ± 0.426
    6.05 ± 0.309
    4.93 ± 0.379
    5.78 ± 0.404
    5.38 ± 0.248
        Japanese: DAS28(ESR): Day 85 (n=16,9,8,9,8)
    -0.83 ± 0.359
    -1.99 ± 0.382
    -1.24 ± 0.362
    -1.78 ± 0.38
    -0.74 ± 0.276
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [93]
    P-value
    = 0.086
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.85
         upper limit
    0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.23
    Notes
    [93] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [94]
    P-value
    = 0.016
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.55
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.99
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.225
    Notes
    [94] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [95]
    P-value
    = 0.059
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.87
         upper limit
    0.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.225
    Notes
    [95] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [96]
    P-value
    = 0.002
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.14
         upper limit
    -0.25
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.227
    Notes
    [96] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [97]
    P-value
    = 0.107
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.87
         upper limit
    0.09
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.241
    Notes
    [97] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [98]
    P-value
    = 0.007
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.64
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.11
         upper limit
    -0.18
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.236
    Notes
    [98] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [99]
    P-value
    = 0.084
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.88
         upper limit
    0.06
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.236
    Notes
    [99] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    European region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [100]
    P-value
    = 0.002
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.73
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    -0.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.238
    Notes
    [100] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 9
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [101]
    P-value
    = 0.785
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    0.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.78
         upper limit
    1.02
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.447
    Notes
    [101] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 10
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [102]
    P-value
    = 0.014
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.13
         upper limit
    -0.26
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.465
    Notes
    [102] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 11
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [103]
    P-value
    = 0.931
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.94
         upper limit
    0.86
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.448
    Notes
    [103] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 12
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (CRP) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [104]
    P-value
    = 0.07
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.86
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.8
         upper limit
    0.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.465
    Notes
    [104] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 13
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [105]
    P-value
    = 0.854
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.08
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.99
         upper limit
    0.82
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.449
    Notes
    [105] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 14
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [106]
    P-value
    = 0.011
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -1.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.19
         upper limit
    -0.31
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.468
    Notes
    [106] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 15
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [107]
    P-value
    = 0.271
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    0.4
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.448
    Notes
    [107] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 16
    Statistical analysis description
    Japanese region: Analysis reported for change from baseline in DAS28 (ESR) at Day 85. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [108]
    P-value
    = 0.031
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    -1.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.97
         upper limit
    -0.1
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.465
    Notes
    [108] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

    Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85

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    End point title
    Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85
    End point description
    DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Remission was defined as less than 2.6 DAS28 (ESR) or DAS28 (CRP) score. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Secondary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        DAS28(CRP)
    14.6
    22.4
    18.8
    23.4
    7.6
        DAS28(ESR)
    6.3
    8.2
    8.3
    6.4
    3.3
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [109]
    P-value
    = 0.238
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.3
         upper limit
    20.5
    Notes
    [109] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [110]
    P-value
    = 0.017
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    14.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.8
         upper limit
    29.7
    Notes
    [110] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [111]
    P-value
    = 0.09
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    11.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    25.4
    Notes
    [111] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    DAS28 (CRP): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [112]
    P-value
    = 0.015
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    15.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.9
         upper limit
    31
    Notes
    [112] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [113]
    P-value
    = 0.412
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.2
         upper limit
    14
    Notes
    [113] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [114]
    P-value
    = 0.237
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    4.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9
         upper limit
    16.4
    Notes
    [114] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [115]
    P-value
    = 0.231
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    5.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.8
         upper limit
    16.8
    Notes
    [115] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    DAS28 (ESR): p-value was calculated using a two-tailed Fisher’s exact test. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [116]
    P-value
    = 0.406
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    3.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.1
         upper limit
    14.4
    Notes
    [116] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.

    Secondary: Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region

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    End point title
    Percentage of Participants who Achieved DAS28 (CRP) and DAS28 (ESR) Remission at Day 85 by Region
    End point description
    DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Remission was defined as less than 2.6 DAS28 (ESR) or DAS28 (CRP) score. DAS28 (CRP) and DAS28 (ESR) for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        European: DAS28(CRP):(n=75,39,41,39,39)
    15.4
    17.1
    17.9
    23.1
    6.7
        European: DAS28(ESR):(n=75,39,41,39,39)
    7.7
    9.8
    7.7
    7.7
    1.3
        Japanese: DAS28(CRP) (n=17,9,8,9,8)
    11.1
    50
    22.2
    25
    11.8
        Japanese: DAS28(ESR) (n=17,9,8,9,8)
    0
    0
    11.1
    0
    11.8
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [117]
    P-value
    = 0.182 [118]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    8.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    24.4
    Notes
    [117] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [118] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [119]
    P-value
    = 0.11 [120]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    10.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    25.5
    Notes
    [119] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [120] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [121]
    P-value
    = 0.104 [122]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    11.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.6
         upper limit
    26.9
    Notes
    [121] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [122] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [123]
    P-value
    = 0.016 [124]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    16.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.5
         upper limit
    32.7
    Notes
    [123] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [124] - European region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    other [125]
    P-value
    = 0.115 [126]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    6.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    19.3
    Notes
    [125] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [126] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [127]
    P-value
    = 0.052 [128]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    8.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.6
         upper limit
    21.6
    Notes
    [127] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [128] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    other [129]
    P-value
    = 0.115 [130]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    6.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    19.3
    Notes
    [129] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [130] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    other [131]
    P-value
    = 0.115 [132]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    6.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    19.3
    Notes
    [131] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [132] - European region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 9
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [133]
    P-value
    = 1 [134]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -27
         upper limit
    34.8
    Notes
    [133] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [134] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 10
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [135]
    P-value
    = 0.059 [136]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    38.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.6
         upper limit
    71.2
    Notes
    [135] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [136] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 11
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [137]
    P-value
    = 0.591 [138]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    10.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -18.2
         upper limit
    46.2
    Notes
    [137] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [138] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 12
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [139]
    P-value
    = 0.57 [140]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    13.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.6
         upper limit
    51.4
    Notes
    [139] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [140] - Japanese region (DAS28 [CRP]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 13
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [141]
    P-value
    = 0.529 [142]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -11.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -35
         upper limit
    22.7
    Notes
    [141] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [142] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 14
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [143]
    P-value
    = 1 [144]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -11.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -37.5
         upper limit
    22.6
    Notes
    [143] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [144] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 15
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [145]
    P-value
    = 1 [146]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -27
         upper limit
    34.8
    Notes
    [145] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [146] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 16
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [147]
    P-value
    = 1 [148]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -11.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -37.5
         upper limit
    22.6
    Notes
    [147] - 95 percent (%) unconditional exact confidence interval was calculated using the method of Agresti and Min, 2001.
    [148] - Japanese region (DAS28 [ESR]): p-value was calculated using a two-tailed Fisher’s exact test.

    Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission

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    End point title
    Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission
    End point description
    DAS28 calculated SJC and TJC using the 28 joints, GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0 = best, 10 = worst) and CRP (mg/L) for DAS28 (CRP) or ESR (mm/hour) for DAS28 (ESR). Total score range: 0-9.4, higher score = more disease activity. DAS28 <3.2 = low disease activity, >=3.2 to 5.1 = moderate to high disease activity and <2.6= remission. Response was defined as 1.2 decrease from baseline in DAS28 (CRP) or DAS28 (ESR) score. Remission was defined as less than 2.6 DAS28 (CRP) or DAS28 (ESR) score. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 169 (follow-up)
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: days
    median (confidence interval 95%)
        DAS28 (CRP) Response
    84 (43 to 99999)
    43 (29 to 58)
    71 (42 to 89)
    42 (29 to 45)
    88 (57 to 88)
        DAS28 (CRP) Remission
    99999 (-99999 to 99999)
    99999 (99999 to 99999)
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
        DAS28 (ESR) Response
    58 (43 to 86)
    30 (29 to 43)
    57 (29 to 71)
    29 (28 to 42)
    85 (57 to 88)
        DAS28 (ESR) Remission
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    99999 (-99999 to 99999)
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.604
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.145
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.282
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.047
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval

    Secondary: Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region

    Close Top of page
    End point title
    Time to Onset for DAS28 (CRP) and DAS (ESR) Response and Remission by Region
    End point description
    DAS28 calculated SJC and TJC using the 28 joints,GH using participant assessment of disease activity (participant rated arthritis activity using the numerical rating scale with 0=best,10=worst) and CRP(mg/L) for DAS28(CRP)orESR(mm/hour) for DAS28(ESR). Total score range:0-9.4, higher score=more disease activity.DAS28<3.2=low disease activity,>=3.2 to 5.1=moderate to high disease activity and<2.6=remission.Response was defined as 1.2 decrease from baseline in DAS28(CRP)orDAS28(ESR) score. Remission was defined as <2.6 DAS28(CRP)orDAS28(ESR) score. Time to response for DAS28(CRP) and DAS28(ESR) by region were reported. Time to remission for DAS28(CRP) and DAS28(ESR) by region were not analyzed because time to remission for the overall study population could not be achieved. The ITT population was analysed and six participants were excluded for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 169 (follow-up)
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: days
    median (confidence interval 95%)
        European: DAS28 (CRP) Response (n=75,39,41,39,39)
    43 (43 to 99999)
    43 (42 to 71)
    50 (29 to 89)
    42 (29 to 57)
    85 (57 to 88)
        Japanese: DAS28 (CRP) Response (n=17,9,8,9,8)
    99999 (-99999 to 99999)
    22.5 (15 to 57)
    87 (30 to 87)
    37 (15 to 57)
    99999 (-99999 to 99999)
        European: DAS28 (ESR) Response (n=75,39,41,39,39)
    57 (30 to 85)
    42 (29 to 43)
    52.5 (29 to 84)
    29 (28 to 42)
    71 (57 to 88)
        Japanese: DAS28 (ESR) Response (n=17,9,8,9,8)
    86 (57 to 86)
    29 (15 to 44)
    44.5 (29 to 99999)
    30 (15 to 44)
    99999 (-99999 to 99999)
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.237
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.005
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.134
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.265
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    European region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.013
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.952
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 9
    Statistical analysis description
    European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.246
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 10
    Statistical analysis description
    European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.004
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 11
    Statistical analysis description
    European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.126
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 12
    Statistical analysis description
    European region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg v Mavrilimumab 100 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 15
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.125
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 14
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.005
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 13
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    = 0.831
    Method
    Logrank
    Confidence interval
    Statistical analysis title
    Statistical Analysis 16
    Statistical analysis description
    Japanese region: Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other
    P-value
    < 0.001
    Method
    Logrank
    Confidence interval

    Secondary: Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission

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    End point title
    Duration of DAS28 (CRP) and DAS28 (ESR) Response and Remission
    End point description
    DAS28 calculated SJC and TJC using 28 joints,GH using participant assessment of disease activity(participant rated arthritis activity using numerical rating scale with 0=best,10=worst) andCRP(mg/L)for DAS28(CRP)or ESR(mm/hour) for DAS28(ESR).Total score range:0-9.4,higher score=more disease activity.DAS28<3.2=low disease activity,>=3.2 to 5.1=moderate to high disease activity and<2.6=remission.Response defined as 1.2 decrease from baseline in DAS28(CRP)or DAS28(ESR)score.Remission defined as<2.6 DAS28(CRP)orDAS28(ESR)score.Expected duration of response(DOR) calculated as response rate(in percentage) multiplied by mean DOR(in days) by using Weibull Model.Duration of DAS28(CRP)andDAS28(ESR) remission were not analyzed because very few participants achieved remission in the overall study population.ITT population (6 participants were excluded for data integrity issues).Here "n" signifies participants who were evaluable for this measure for specified parameter for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 169
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: Percentage of days
    number (not applicable)
        DAS28 (CRP) Response
    42.19
    81.89
    54.8
    83.07
    43.4
        DAS28 (ESR) Response
    52.96
    71.14
    75.97
    96.52
    46.11
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [149]
    P-value
    = 0.486
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    1.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.78
         upper limit
    1.69
    Notes
    [149] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [150]
    P-value
    = 0.015
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    1.54
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.09
         upper limit
    2.18
    Notes
    [150] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [151]
    P-value
    = 0.006
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    1.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.15
         upper limit
    2.36
    Notes
    [151] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis reported for DAS28 (ESR) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [152]
    P-value
    < 0.001
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    2.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.49
         upper limit
    2.93
    Notes
    [152] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [153]
    P-value
    = 0.906
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    0.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.61
         upper limit
    1.55
    Notes
    [153] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [154]
    P-value
    < 0.001
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    1.89
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.31
         upper limit
    2.71
    Notes
    [154] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [155]
    P-value
    = 0.272
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    1.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.83
         upper limit
    1.91
    Notes
    [155] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis reported for DAS28 (CRP) response. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [156]
    P-value
    < 0.001
    Method
    Exponential,Weibull and Log normal model
    Parameter type
    Ratio of expected duration of response
    Point estimate
    1.91
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.34
         upper limit
    2.72
    Notes
    [156] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

    Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85

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    End point title
    Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85
    End point description
    ACR20, ACR50, and ACR70, were defined as greater than or equal to (>=) 20 percent (%),>=50%, or >=70% improvement, respectively, in: swollen joint count and tender joint count and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Secondary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        ACR20
    41.7
    57.1
    37.5
    70.2
    37
        ACR50
    20.8
    30.6
    16.7
    34
    12
        ACR70
    4.2
    10.2
    6.3
    14.9
    5.4
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [157]
    P-value
    = 0.589 [158]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    4.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -12.1
         upper limit
    22
    Notes
    [157] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [158] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [159]
    P-value
    = 0.032 [160]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    20.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.8
         upper limit
    36.7
    Notes
    [159] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [160] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [161]
    P-value
    = 1 [162]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16
         upper limit
    18
    Notes
    [161] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [162] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [163]
    P-value
    < 0.001 [164]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    33.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.6
         upper limit
    48.6
    Notes
    [163] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [164] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test-
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [165]
    P-value
    = 0.212 [166]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    8.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.5
         upper limit
    23.6
    Notes
    [165] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [166] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [167]
    P-value
    = 0.011 [168]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    18.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.8
         upper limit
    34
    Notes
    [167] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [168] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [169]
    P-value
    = 0.446 [170]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    4.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7
         upper limit
    19.1
    Notes
    [169] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [170] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [171]
    P-value
    = 0.003 [172]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    22.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.6
         upper limit
    37.8
    Notes
    [171] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [172] - ACR50: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 9
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [173]
    P-value
    = 1 [174]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.9
         upper limit
    9.7
    Notes
    [173] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [174] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 10
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [175]
    P-value
    = 0.317 [176]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    4.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.1
         upper limit
    17.5
    Notes
    [175] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [176] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 11
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [177]
    P-value
    = 1 [178]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.2
         upper limit
    12.1
    Notes
    [177] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [178] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 12
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [179]
    P-value
    = 0.106 [180]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    9.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.5
         upper limit
    23.5
    Notes
    [179] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [180] - ACR70: p-value was calculated using a two-tailed Fisher’s exact test.

    Secondary: Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region

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    End point title
    Percentage of Participants who Achieved American College of Rheumatology 20 (ACR20), ACR50 and ACR70 Responses at Day 85 by Region
    End point description
    ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. Data for the European and Japanese regions were reported. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: percentage of participants
    number (not applicable)
        European: ACR20 (n=75,39,41,39,39)
    41
    56.1
    41
    69.2
    40
        Japanese: ACR20 (n=17,9,8,9,8)
    44.4
    62.5
    22.2
    75
    23.5
        European: ACR50 (n=75,39,41,39,39)
    23.1
    29.3
    20.5
    30.8
    12
        Japanese: ACR50 (n=17,9,8,9,8)
    11.1
    37.5
    0
    50
    11.8
        European: ACR70 (n=75,39,41,39,39)
    5.1
    9.8
    7.7
    17.9
    4
        Japanese: ACR70 (n=17,9,8,9,8)
    0
    12.5
    0
    0
    11.8
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [181]
    P-value
    = 1 [182]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.7
         upper limit
    20.4
    Notes
    [181] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [182] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [183]
    P-value
    = 0.12 [184]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    16.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.1
         upper limit
    34.4
    Notes
    [183] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001
    [184] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [185]
    P-value
    = 1 [186]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -17.7
         upper limit
    20.4
    Notes
    [185] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [186] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [187]
    P-value
    = 0.005 [188]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    29.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.7
         upper limit
    46.1
    Notes
    [187] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [188] - European region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [189]
    P-value
    = 0.382 [190]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    20.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -16.4
         upper limit
    55.9
    Notes
    [189] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001
    [190] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [191]
    P-value
    = 0.087 [192]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.7
         upper limit
    69.6
    Notes
    [191] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [192] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [193]
    P-value
    = 1 [194]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -1.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -33.7
         upper limit
    35.7
    Notes
    [193] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001
    [194] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [195]
    P-value
    = 0.028 [196]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    51.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    8.2
         upper limit
    77
    Notes
    [195] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [196] - Japanese region: ACR20 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 9
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [197]
    P-value
    = 0.175 [198]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    11.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.9
         upper limit
    27.9
    Notes
    [197] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [198] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 11
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [199]
    P-value
    = 0.271 [200]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    8.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.1
         upper limit
    24.9
    Notes
    [199] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [200] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 10
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [201]
    P-value
    = 0.026 [202]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    17.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.4
         upper limit
    34.1
    Notes
    [201] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [202] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 12
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [203]
    P-value
    = 0.021 [204]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    18.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    3.4
         upper limit
    36
    Notes
    [203] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [204] - European region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 14
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [205]
    P-value
    = 0.283 [206]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    25.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.8
         upper limit
    63.2
    Notes
    [205] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [206] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 13
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [207]
    P-value
    = 1 [208]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -27
         upper limit
    34.8
    Notes
    [207] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [208] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 15
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [209]
    P-value
    = 0.529 [210]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -11.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -35
         upper limit
    22.7
    Notes
    [209] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [210] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 16
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [211]
    P-value
    = 0.059 [212]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    38.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.6
         upper limit
    71.2
    Notes
    [211] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [212] - Japanese region: ACR50 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 17
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [213]
    P-value
    = 1 [214]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7
         upper limit
    14.2
    Notes
    [213] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [214] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 18
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [215]
    P-value
    = 0.242 [216]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    5.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.7
         upper limit
    19.4
    Notes
    [215] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [216] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 19
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    140
    Analysis specification
    Pre-specified
    Analysis type
    other [217]
    P-value
    = 0.41 [218]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    3.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.1
         upper limit
    16.9
    Notes
    [217] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [218] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 20
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [219]
    P-value
    = 0.03 [220]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    13.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.7
         upper limit
    29.5
    Notes
    [219] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [220] - European region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 21
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [221]
    P-value
    = 0.529 [222]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -11.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -35
         upper limit
    22.7
    Notes
    [221] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [222] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 22
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    other [223]
    P-value
    = 1 [224]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    0.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -26.7
         upper limit
    39.5
    Notes
    [223] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [224] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 23
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg) v Mavrilimumab 50 mg
    Number of subjects included in analysis
    188
    Analysis specification
    Pre-specified
    Analysis type
    other [225]
    P-value
    = 0.529 [226]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -11.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -35
         upper limit
    22.7
    Notes
    [225] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [226] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.
    Statistical analysis title
    Statistical Analysis 24
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    139
    Analysis specification
    Pre-specified
    Analysis type
    other [227]
    P-value
    = 1 [228]
    Method
    Fisher exact
    Parameter type
    Percent difference
    Point estimate
    -11.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -37.5
         upper limit
    22.6
    Notes
    [227] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    [228] - Japanese region: ACR70 - p-value was calculated using a two-tailed Fisher’s exact test.

    Secondary: Number of Participants who Achieved ACR Categorical Responses

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    End point title
    Number of Participants who Achieved ACR Categorical Responses
    End point description
    ACR20, ACR50, and ACR70, were defined as >=20%, >=50%, or >=70% improvement, respectively, in: SJC and TJC and >=20%, >=50%, or >=70% improvement, respectively, in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the HAQ); and CRP. ACR responses were categorized as "No response", "ACR20 but not ACR50", "ACR50 but not ACR70", and "ACR70". The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues.
    End point type
    Secondary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    48
    49
    48
    47
    92
    Units: participants
        No response
    28
    21
    30
    14
    58
        ACR20 but not ACR50
    10
    13
    10
    17
    23
        ACR50 but not ACR70
    8
    10
    5
    9
    6
        ACR70
    2
    5
    3
    7
    5
    No statistical analyses for this end point

    Secondary: Continuous ACR (ACRn) Score

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    End point title
    Continuous ACR (ACRn) Score
    End point description
    ACR score - continuous (ACRn) was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement. The ITT population analysis set included all randomized participants regardless of whether participants received any investigational product. Six participants were excluded from the ITT population for data integrity issues. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure
    End point type
    Secondary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    44
    47
    45
    46
    84
    Units: units on a scale
        arithmetic mean (standard error)
    19.13 ± 5.818
    26.31 ± 5.652
    12.17 ± 5.786
    37.11 ± 5.723
    5.09 ± 4.23
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    other [229]
    P-value
    = 0.051
    Method
    Repeated measures model
    Parameter type
    Adjusted Mean difference
    Point estimate
    14.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.05
         upper limit
    28.15
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.162
    Notes
    [229] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    other [230]
    P-value
    = 0.003
    Method
    Repeated measures model
    Parameter type
    Adjusted Mean difference
    Point estimate
    21.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    7.39
         upper limit
    35.07
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.028
    Notes
    [230] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    other [231]
    P-value
    = 0.322
    Method
    Repeated measures model
    Parameter type
    Adjusted Mean difference
    Point estimate
    7.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.96
         upper limit
    21.14
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.136
    Notes
    [231] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    other [232]
    P-value
    < 0.001
    Method
    Repeated measures model
    Parameter type
    Adjusted Mean difference
    Point estimate
    32.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    18.08
         upper limit
    45.98
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.085
    Notes
    [232] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

    Secondary: Continuous ACR (ACRn) Score by Region

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    End point title
    Continuous ACR (ACRn) Score by Region
    End point description
    ACR score - continuous (ACRn) was defined as the minimum of the percentage improvement in TJC, SJC and the median of the percentage improvements in the other five components of the ACR criteria (participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; disability index of the HAQ; and CRP). Total score range was -100 to 100, where negative numbers indicated worsening and positive numbers indicated improvement. Data for European and Japanese regions were reported. The ITT population (Six participants were excluded from the ITT population for data integrity issues). Here “N” (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for this measure for the specified region for each arm, respectively.
    End point type
    Secondary
    End point timeframe
    Day 85
    End point values
    Mavrilimumab 10 milligram (mg) Mavrilimumab 30 mg Mavrilimumab 50 mg Mavrilimumab 100 mg Placebo
    Number of subjects analysed
    44
    47
    45
    46
    84
    Units: units on a scale
    arithmetic mean (standard error)
        European region (n=69,36,39,38,38)
    19.18 ± 6.489
    24.12 ± 6.263
    12.53 ± 6.356
    36.06 ± 6.356
    4.71 ± 4.689
        Japanese region (n=15,8,8,7,8)
    18.09 ± 13.843
    37.22 ± 13.843
    10.2 ± 14.799
    42.09 ± 13.843
    5.99 ± 10.06
    Statistical analysis title
    Statistical Analysis 1
    Statistical analysis description
    Analysis reported for European region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    other [233]
    P-value
    = 0.071
    Method
    Repeated measures model
    Parameter type
    Adjusted Mean difference
    Point estimate
    14.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.24
         upper limit
    30.22
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.981
    Notes
    [233] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 2
    Statistical analysis description
    Analysis reported for European region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    other [234]
    P-value
    = 0.013
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    19.43
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    4.06
         upper limit
    34.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.798
    Notes
    [234] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 3
    Statistical analysis description
    Analysis reported for European region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    other [235]
    P-value
    = 0.32
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    7.84
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.68
         upper limit
    23.36
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.873
    Notes
    [235] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 4
    Statistical analysis description
    Analysis reported for European region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    other [236]
    P-value
    < 0.001
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    31.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    15.85
         upper limit
    46.89
    Variability estimate
    Standard error of the mean
    Dispersion value
    7.873
    Notes
    [236] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 5
    Statistical analysis description
    Analysis reported for Japanese region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 10 milligram (mg)
    Number of subjects included in analysis
    128
    Analysis specification
    Pre-specified
    Analysis type
    other [237]
    P-value
    = 0.483
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    12.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -22.41
         upper limit
    46.64
    Variability estimate
    Standard error of the mean
    Dispersion value
    17.089
    Notes
    [237] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 6
    Statistical analysis description
    Analysis reported for Japanese region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 30 mg
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    other [238]
    P-value
    = 0.075
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    31.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.28
         upper limit
    65.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    17.089
    Notes
    [238] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 7
    Statistical analysis description
    Analysis reported for Japanese region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 50 mg
    Number of subjects included in analysis
    129
    Analysis specification
    Pre-specified
    Analysis type
    other [239]
    P-value
    = 0.815
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    4.22
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -31.89
         upper limit
    40.32
    Variability estimate
    Standard error of the mean
    Dispersion value
    17.872
    Notes
    [239] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.
    Statistical analysis title
    Statistical Analysis 8
    Statistical analysis description
    Analysis reported for Japanese region. Analysis Type used was dose escalation.
    Comparison groups
    Placebo v Mavrilimumab 100 mg
    Number of subjects included in analysis
    130
    Analysis specification
    Pre-specified
    Analysis type
    other [240]
    P-value
    = 0.041
    Method
    Repeated measures model
    Parameter type
    Adjusted mean difference
    Point estimate
    36.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.58
         upper limit
    70.63
    Variability estimate
    Standard error of the mean
    Dispersion value
    17.089
    Notes
    [240] - 95 percent (%) unconditional exact confidence interval calculated using the method of Agresti and Min, 2001.

    Secondary: Swollen and Tender Joint Count

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    End point title
    Swollen and Tender Joint Count
    End point description
    Number of swollen joints was de