Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35239   clinical trials with a EudraCT protocol, of which   5761   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects with Inactive Non-infectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis – Including a Sub-study in Japanese Patients

    Summary
    EudraCT number
    2009-016008-22
    Trial protocol
    FR   ES   BE   PT   GB   NL   DE   DK   AT   IT   CZ   GR  
    Global end of trial date
    14 May 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    29 May 2016
    First version publication date
    29 May 2016
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    M10-880
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01124838
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    AbbVie Deutschland GmbH & Co.KG
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
    Public contact
    Global Medical Information, AbbVie, 011 800-633-9110,
    Scientific contact
    Andrew Payne, AbbVie, andy.payne@abbvie.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 May 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 May 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of this study is to evaluate the efficacy and safety of adalimumab 80 mg loading dose followed by 40 mg dose given every other week subcutaneously starting at Week 1 compared with placebo in patients with inactive non-infectious intermediate uveitis, posterior uveitis, or panuveitis.
    Protection of trial subjects
    The study was conducted in accordance with the protocol, ICH guidelines, applicable regulations and guidelines governing clinical study conduct, and the ethical principles that have their origin in the Declaration of Helsinki and all applicable local regulations. The investigator or his/her representative explained the nature of the study to the subject, and answered all questions regarding the study. Prior to any study-related screening procedures being performed on the subject, the informed consent statement was reviewed and signed and dated by the subject, the person who administered the informed consent, and any other signatories according to local requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    10 Aug 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 4
    Country: Number of subjects enrolled
    Poland: 11
    Country: Number of subjects enrolled
    Portugal: 3
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    United Kingdom: 18
    Country: Number of subjects enrolled
    Austria: 8
    Country: Number of subjects enrolled
    Belgium: 31
    Country: Number of subjects enrolled
    Czech Republic: 1
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Greece: 2
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Argentina: 20
    Country: Number of subjects enrolled
    Australia: 7
    Country: Number of subjects enrolled
    Brazil: 3
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    Israel: 3
    Country: Number of subjects enrolled
    Japan: 32
    Country: Number of subjects enrolled
    Mexico: 4
    Country: Number of subjects enrolled
    Switzerland: 4
    Country: Number of subjects enrolled
    United States: 61
    Worldwide total number of subjects
    261
    EEA total number of subjects
    116
    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)
    246
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This study includes a Japan sub-study. A total of 261 subjects with inactive non-infectious intermediate uveitis, posterior uveitis or panuveitis were randomized at 72 study sites worldwide; 229 participants at 62 study sites in Australia, Israel, Latin America, North America, and Europe (Main Study), and 32 participants at 10 study sites in Japan.

    Pre-assignment
    Screening details
    Participants were randomized in a 1:1 ratio double-masked fashion using baseline immunosuppressant (IMM) usage as the stratification factor. Participants in the Japan sub-study were randomized in a separate stratum with no stratification by baseline IMM usage. Study completion is defined as meeting treatment failure or reaching study Week 80.

    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
    Placebo
    Arm description
    Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered by subcutaneous injection

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper schedule in which all subjects continuing in the study were to discontinue prednisone no later than Week 19.

    Arm title
    Adalimumab
    Arm description
    Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Humira
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Administered subcutaneously as an 80 mg loading dose (2 syringes) at Baseline followed by 40 mg eow starting at Week 1.

    Investigational medicinal product name
    Prednisone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Administered orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper schedule in which all subjects continuing in the study were to discontinue prednisone no later than Week 19.

    Number of subjects in period 1
    Placebo Adalimumab
    Started
    130
    131
    Enrolled in Main Study
    114
    115 [1]
    Enrolled in Japan Sub-study
    16 [2]
    16 [3]
    Completed
    112
    116
    Not completed
    18
    15
         Other
             4
             2
         Adverse event
             7
             11
         Lack of efficacy
             2
             -
         Consent withdrawn by subject
             3
             2
         Lost to follow-up
             2
             -
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only includes subjects who enrolled outside of Japan
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only includes subjects who enrolled in Japan
    [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Only includes subjects who enrolled in Japan

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Reporting group title
    Adalimumab
    Reporting group description
    Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Reporting group values
    Placebo Adalimumab Total
    Number of subjects
    130 131 261
    Age categorical
    Units: Subjects
        < 65 years
    121 125 246
        ≥ 65 years
    9 6 15
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    43.22 ± 14.026 43.18 ± 12.719 -
    Gender categorical
    Units: Subjects
        Female
    83 75 158
        Male
    47 56 103
    Race
    Units: Subjects
        White
    96 96 192
        Black
    8 6 14
        Asian
    19 19 38
        American Indian/Alaskan Native
    1 0 1
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Other
    5 9 14
        Multi Race
    1 1 2
    Type of Uveitis
    Units: Subjects
        Intermediate
    30 17 47
        Posterior
    36 41 77
        Panuveitis
    63 71 134
        Intermediate/Posterior
    1 2 3
    Diagnosis
    Units: Subjects
        Idiopathic
    45 33 78
        Birdshot Choroidopathy
    16 15 31
        Multifocal Choroiditis and Panuveitis
    2 5 7
        Vogt Koyanagi Harada
    30 34 64
        Sarcoid
    20 22 42
        Behcet's
    7 10 17
        Other
    10 12 22
    Eye Affected
    Units: Subjects
        Left
    3 3 6
        Right
    5 2 7
        Both
    122 126 248
    History of Infectious Uveitis
    Units: Subjects
        Yes
    0 0 0
        No
    130 131 261
    Duration of Uveitis
    Units: months
        arithmetic mean (standard deviation)
    59.36 ± 64.753 58.35 ± 61.834 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Reporting group title
    Adalimumab
    Reporting group description
    Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Subject analysis set title
    Main Study: Placebo
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects, excluding those enrolled in the Japan sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Subjects continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Subject analysis set title
    Main Study: Adalimumab
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects, excluding those enrolled in the Japan sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Subjects continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Subject analysis set title
    Integrated Study (Main + Japan Sub-study): Placebo
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects, including those enrolled in the Main Study and the Japan Sub-study, received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Subjects continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Subject analysis set title
    Integrated Study (Main + Japan Sub-study): Adalimumab
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    Subjects, including those enrolled in the Main Study and the Japan Sub-study, received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Subjects continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Primary: Time to Treatment Failure on or After Week 2

    Close Top of page
    End point title
    Time to Treatment Failure on or After Week 2
    End point description
    Treatment failure was defined by the occurrence of a uveitis flare (the inability to maintain disease control). To be considered treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye at Week 2 or all other visits: • New active, inflammatory chorioretinal, and/or inflammatory retinal vascular lesions relative to Baseline • 2-step increase relative to Baseline in anterior chamber cell grade or vitreous haze grade • Worsening of best corrected visual acuity by ≥ 15 letters relative to baseline. Time to treatment failure was analyzed using the Kaplan-Meier method. Dropouts for reasons other than treatment failure at any time during the study were censored at the drop out date. The primary analysis was performed in the intent-to-treat (ITT) population which included all randomized subjects recruited outside Japan; 3 subjects at 2 sites were excluded from the ITT due to incomplete efficacy source data and compliance issues. "99999" indicates values not estimable.
    End point type
    Primary
    End point timeframe
    From Baseline until end of study (up to 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    111
    115
    127
    131
    Units: months
        median (inter-quartile range (Q1-Q3))
    8.3 (3 to 99999)
    99999 (4.7 to 99999)
    5.6 (2.6 to 99999)
    99999 (3.9 to 99999)
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The primary analysis of the primary endpoint was performed on Main Study data, excluding the Japanese sub-study. The statistical test was performed at a 2-sided significance level of 0.05. The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment as factor.
    Comparison groups
    Main Study: Adalimumab v Main Study: Placebo
    Number of subjects included in analysis
    226
    Analysis specification
    Pre-specified
    Analysis type
    other [1]
    P-value
    = 0.004
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.57
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.39
         upper limit
    0.84
    Notes
    [1] - Difference
    Statistical analysis title
    Additional Analysis – Integrated Study
    Statistical analysis description
    An additional analysis of the primary endpoint was performed using the Integrated Study data (Main Study + Japan sub-study). The statistical test was performed at a 2-sided significance level of 0.05. The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment and race (Japanese versus non-Japanese) as factors.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    258
    Analysis specification
    Pre-specified
    Analysis type
    other [2]
    P-value
    < 0.001
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.52
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.37
         upper limit
    0.74
    Notes
    [2] - Difference

    Secondary: Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit
    End point description
    Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: Grade 0 = < 1 cell Grade 0.5+ = 1 - 5 cells Grade 1+ = 6 - 15 cells Grade 2+ = 16 - 25 cells Grade 3+ = 26 - 50 cells Grade 4+ = > 50 cells. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and at the Final/Early Termination Visit (up to 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    110 [3]
    115 [4]
    126 [5]
    131 [6]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Left eye
    0.57 ± 1.001
    0.41 ± 0.969
    0.61 ± 1.005
    0.46 ± 0.996
        Right eye
    0.53 ± 0.963
    0.4 ± 0.927
    0.6 ± 0.992
    0.44 ± 0.95
    Notes
    [3] - Participants with values at both time points
    [4] - Participants with values at both time points
    [5] - Participants with values at both time points
    [6] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Adalimumab v Main Study: Placebo
    Number of subjects included in analysis
    225
    Analysis specification
    Pre-specified
    Analysis type
    other [7]
    P-value
    = 0.218 [8]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.14
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.37
         upper limit
    0.08
    Notes
    [7] - Difference
    [8] - From ANOVA of change from baseline to final/early termination visit with treatment as factor adjusted for clustered observations (i.e., observations from each of the subject's eyes).
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    257
    Analysis specification
    Pre-specified
    Analysis type
    other [9]
    P-value
    = 0.164 [10]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.15
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.36
         upper limit
    0.06
    Notes
    [9] - Difference
    [10] - From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors adjusted for clustered observations (i.e., observations from each of the subject's eyes).

    Secondary: Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Change in Vitreous Haze (VH) Grade in Each Eye From Baseline to the Final/Early Termination Visit
    End point description
    Vitreous haze was measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to National Eye Institute (NEI) and SUN criteria: Grade 0: No evident vitreous haze; Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and Final/Early Termination Visit (up to 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    110 [11]
    115 [12]
    126 [13]
    131 [14]
    Units: units on a scale
    arithmetic mean (standard deviation)
        Left eye
    0.33 ± 0.733
    0.16 ± 0.601
    0.35 ± 0.749
    0.18 ± 0.614
        Right eye
    0.27 ± 0.605
    0.18 ± 0.604
    0.36 ± 0.729
    0.18 ± 0.602
    Notes
    [11] - Participants with values at both time points
    [12] - Participants with values at both time points
    [13] - Participants with values at both time points
    [14] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Adalimumab v Main Study: Placebo
    Number of subjects included in analysis
    225
    Analysis specification
    Pre-specified
    Analysis type
    other [15]
    P-value
    = 0.07 [16]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.28
         upper limit
    0.01
    Notes
    [15] - Difference
    [16] - From ANOVA of change from baseline to final/early termination visit with treatment as factor adjusted for clustered observations.
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    257
    Analysis specification
    Pre-specified
    Analysis type
    other [17]
    P-value
    = 0.016 [18]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.17
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.31
         upper limit
    -0.03
    Notes
    [17] - Difference
    [18] - From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors adjusted for clustered observations.

    Secondary: Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Baseline to the Final/Early Termination Visit
    End point description
    Using corrective lenses based on that visit's refraction testing, subject's best corrected visual acuity was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and Final/Early Termination Visit (up to 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    110 [19]
    115 [20]
    126 [21]
    131 [22]
    Units: logMAR
    arithmetic mean (standard deviation)
        Left eye
    0.06 ± 0.239
    0.01 ± 0.251
    0.07 ± 0.23
    0.02 ± 0.241
        Right eye
    0.02 ± 0.198
    -0.01 ± 0.165
    0.04 ± 0.216
    0 ± 0.169
    Notes
    [19] - Participants with values at both time points
    [20] - Participants with values at both time points
    [21] - Participants with values at both time points
    [22] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Placebo v Main Study: Adalimumab
    Number of subjects included in analysis
    225
    Analysis specification
    Pre-specified
    Analysis type
    other [23]
    P-value
    = 0.096 [24]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.08
         upper limit
    0.01
    Notes
    [23] - Difference
    [24] - From ANOVA of change from baseline to final/early termination visit with treatment as factor adjusted for clustered observations.
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    257
    Analysis specification
    Pre-specified
    Analysis type
    other [25]
    P-value
    = 0.044 [26]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.09
         upper limit
    0
    Notes
    [25] - Difference
    [26] - From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors adjusted for clustered observations.

    Secondary: Time to Optimal Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 2

    Close Top of page
    End point title
    Time to Optimal Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 2
    End point description
    Optical coherence tomography was performed at every visit using 1 of 3 approved machines. Images were evaluated by a central reader. Macular edema was defined as cystoid macular edema. OCT evidence of macular edema on or after Week 2 was to be counted as an event. Dropouts due to reasons other than OCT evidence of macular edema were to be considered as censored observations at the time of dropping out. This endpoint was only analyzed in subjects without macular edema at Baseline. "99999" indicates values not estimable.
    End point type
    Secondary
    End point timeframe
    From Baseline until the Final Visit (up to 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    95 [27]
    90 [28]
    106 [29]
    102 [30]
    Units: months
        median (inter-quartile range (Q1-Q3))
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Notes
    [27] - Subjects without macular edema at Baseline
    [28] - Subjects without macular edema at Baseline
    [29] - Subjects without macular edema at Baseline
    [30] - Subjects without macular edema at Baseline
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%. The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment as factor.
    Comparison groups
    Main Study: Placebo v Main Study: Adalimumab
    Number of subjects included in analysis
    185
    Analysis specification
    Pre-specified
    Analysis type
    other [31]
    P-value
    = 0.491
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.34
         upper limit
    1.69
    Notes
    [31] - Difference
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%. The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment and race (Japanese versus non-Japanese) as factors.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    208
    Analysis specification
    Pre-specified
    Analysis type
    other [32]
    P-value
    = 0.185
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.28
         upper limit
    1.28
    Notes
    [32] - Difference

    Secondary: Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Percent Change in Central Retinal Thickness in Each Eye From Baseline to the Final/Early Termination Visit
    End point description
    Central retinal thickness was measured using OCT and assessed by a central reader. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and Final/Early Termination Visit (up to 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    108 [33]
    114 [34]
    124 [35]
    130 [36]
    Units: percent change
    arithmetic mean (standard deviation)
        Left eye (N = 107, 114, 122, 130)
    6.4 ± 20.67
    4.5 ± 29.82
    6.3 ± 19.75
    5.2 ± 29.91
        Right eye (N = 108, 113, 124, 129)
    7.7 ± 28.88
    5.4 ± 34.83
    9.9 ± 30.79
    3.9 ± 33.34
    Notes
    [33] - Participants with values at both time points
    [34] - Participants with values at both time points
    [35] - Participants with values at both time points
    [36] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Adalimumab v Main Study: Placebo
    Number of subjects included in analysis
    222
    Analysis specification
    Pre-specified
    Analysis type
    other [37]
    P-value
    = 0.451 [38]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -2.3
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -8.5
         upper limit
    3.8
    Notes
    [37] - Difference
    [38] - From ANOVA of change from baseline to final/early termination visit with treatment and OCT machine as factors adjusted for clustered observations.
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    254
    Analysis specification
    Pre-specified
    Analysis type
    other [39]
    P-value
    = 0.174 [40]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -3.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.7
         upper limit
    1.8
    Notes
    [39] - Difference
    [40] - From ANOVA of change from baseline to final/early termination visit with treatment, race (Japanese versus non-Japanese) and OCT machine as factors adjusted for clustered observations.

    Secondary: Change in Visual Functioning Questionnaire 25 (VFQ-25) Total Score From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Change in Visual Functioning Questionnaire 25 (VFQ-25) Total Score From Baseline to the Final/Early Termination Visit
    End point description
    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The overall composite score ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and Final/Early Termination Visit (up 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    109 [41]
    115 [42]
    125 [43]
    131 [44]
    Units: units on a scale
        arithmetic mean (standard deviation)
    1.24 ± 10.698
    3.36 ± 11.73
    1 ± 10.225
    2.79 ± 12.018
    Notes
    [41] - Participants with values at both time points
    [42] - Participants with values at both time points
    [43] - Participants with values at both time points
    [44] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Placebo v Main Study: Adalimumab
    Number of subjects included in analysis
    224
    Analysis specification
    Pre-specified
    Analysis type
    other [45]
    P-value
    = 0.16 [46]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    2.12
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.84
         upper limit
    5.08
    Notes
    [45] - Difference
    [46] - From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    256
    Analysis specification
    Pre-specified
    Analysis type
    other [47]
    P-value
    = 0.205 [48]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    1.77
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.97
         upper limit
    4.52
    Notes
    [47] - Difference
    [48] - From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors.

    Secondary: Change in VFQ-25 Subscore Distance Vision From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Change in VFQ-25 Subscore Distance Vision From Baseline to the Final/Early Termination Visit
    End point description
    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 distance vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and Final/Early Termination Visit (up 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    109 [49]
    115 [50]
    125 [51]
    131 [52]
    Units: units on a scale
        arithmetic mean (standard deviation)
    0.76 ± 16.248
    2.64 ± 17.165
    0.6 ± 15.978
    2.96 ± 17.121
    Notes
    [49] - Participants with values at both time points
    [50] - Participants with values at both time points
    [51] - Participants with values at both time points
    [52] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Placebo v Main Study: Adalimumab
    Number of subjects included in analysis
    224
    Analysis specification
    Pre-specified
    Analysis type
    other [53]
    P-value
    = 0.401 [54]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    1.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.53
         upper limit
    6.29
    Notes
    [53] - Difference
    [54] - From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    256
    Analysis specification
    Pre-specified
    Analysis type
    other [55]
    P-value
    = 0.256 [56]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    2.36
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.73
         upper limit
    6.45
    Notes
    [55] - Difference
    [56] - From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors.

    Secondary: Change in VFQ-25 Subscore Near Vision From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Change in VFQ-25 Subscore Near Vision From Baseline to the Final/Early Termination Visit
    End point description
    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The near vision subscore is calculated from the answers to 3 near vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and Final/Early Termination Visit (up 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    109 [57]
    115 [58]
    125 [59]
    131 [60]
    Units: units on a scale
        arithmetic mean (standard deviation)
    3.98 ± 17.397
    3.88 ± 18.302
    3.73 ± 17.17
    2.89 ± 20.503
    Notes
    [57] - Participants with values at both time points
    [58] - Participants with values at both time points
    [59] - Participants with values at both time points
    [60] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Placebo v Main Study: Adalimumab
    Number of subjects included in analysis
    224
    Analysis specification
    Pre-specified
    Analysis type
    other [61]
    P-value
    = 0.967 [62]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.81
         upper limit
    4.61
    Notes
    [61] - Difference
    [62] - From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    256
    Analysis specification
    Pre-specified
    Analysis type
    other [63]
    P-value
    = 0.714 [64]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.87
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.53
         upper limit
    3.79
    Notes
    [63] - Difference
    [64] - From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese versus non-Japanese) as factors.

    Secondary: Change in VFQ-25 Subscore Ocular Pain From Baseline to the Final/Early Termination Visit

    Close Top of page
    End point title
    Change in VFQ-25 Subscore Ocular Pain From Baseline to the Final/Early Termination Visit
    End point description
    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The ocular pain subscore is calculated from the answers to 2 eye pain questions and ranges from 0 to 100, where higher scores or increases in score indicate less pain. This endpoint was analyzed in the intent-to-treat population; last observation carried forward (LOCF) imputation was used.
    End point type
    Secondary
    End point timeframe
    Baseline and Final/Early Termination visit (up to 80 weeks)
    End point values
    Main Study: Placebo Main Study: Adalimumab Integrated Study (Main + Japan Sub-study): Placebo Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects analysed
    109 [65]
    115 [66]
    125 [67]
    131 [68]
    Units: units on a scale
        arithmetic mean (standard deviation)
    2.87 ± 17.233
    3.42 ± 21.32
    2.6 ± 17.339
    2.15 ± 21.689
    Notes
    [65] - Participants with values at both time points
    [66] - Participants with values at both time points
    [67] - Participants with values at both time points
    [68] - Participants with values at both time points
    Statistical analysis title
    Primary Analysis - Main Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Main Study: Placebo v Main Study: Adalimumab
    Number of subjects included in analysis
    224
    Analysis specification
    Pre-specified
    Analysis type
    other [69]
    P-value
    = 0.83 [70]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    0.56
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.56
         upper limit
    5.68
    Notes
    [69] - Difference
    [70] - From ANOVA of change from baseline to final/early termination visit with treatment as a factor.
    Statistical analysis title
    Additional Analysis - Integrated Study
    Statistical analysis description
    The statistical test for the ranked secondary variables was carried out in hierarchical order at the significance level of 5%.
    Comparison groups
    Integrated Study (Main + Japan Sub-study): Placebo v Integrated Study (Main + Japan Sub-study): Adalimumab
    Number of subjects included in analysis
    256
    Analysis specification
    Pre-specified
    Analysis type
    other [71]
    P-value
    = 0.842 [72]
    Method
    ANOVA
    Parameter type
    Mean Difference
    Point estimate
    -0.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.32
         upper limit
    4.34
    Notes
    [71] - Difference
    [72] - From ANOVA of change from baseline to final/early termination visit with treatment and race (Japanese vs. non-Japanese) as factors.

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 147 days in the placebo arm and 245 days in the adalimumab arm.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received placebo subcutaneous injection at Baseline followed by every other week (eow) dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 to 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Reporting group title
    Adalimumab
    Reporting group description
    Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses eow starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper until Week 19.

    Serious adverse events
    Placebo Adalimumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 130 (7.69%)
    8 / 131 (6.11%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    Vascular disorders
    Aortic Dissection
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep Vein Thrombosis
         subjects affected / exposed
    2 / 130 (1.54%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive Crisis
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Fibula Fracture
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lung Adenocarcinoma Stage Iv
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac Tamponade
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dysarthria
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status Migrainosus
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Blindness Transient
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Choroidal Neovascularisation
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retinal Detachment
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subretinal Fluid
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis Aseptic
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia Legionella
         subjects affected / exposed
    0 / 130 (0.00%)
    1 / 131 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 130 (0.77%)
    0 / 131 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo Adalimumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    78 / 130 (60.00%)
    88 / 131 (67.18%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    5 / 130 (3.85%)
    7 / 131 (5.34%)
         occurrences all number
    5
    7
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    1 / 130 (0.77%)
    9 / 131 (6.87%)
         occurrences all number
    1
    14
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    1 / 130 (0.77%)
    8 / 131 (6.11%)
         occurrences all number
    1
    11
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 130 (4.62%)
    11 / 131 (8.40%)
         occurrences all number
    6
    11
    Nervous system disorders
    Headache
         subjects affected / exposed
    17 / 130 (13.08%)
    17 / 131 (12.98%)
         occurrences all number
    22
    22
    Eye disorders
    Cystoid Macular Oedema
         subjects affected / exposed
    7 / 130 (5.38%)
    7 / 131 (5.34%)
         occurrences all number
    11
    8
    Dry Eye
         subjects affected / exposed
    8 / 130 (6.15%)
    5 / 131 (3.82%)
         occurrences all number
    8
    5
    Eye Pain
         subjects affected / exposed
    6 / 130 (4.62%)
    9 / 131 (6.87%)
         occurrences all number
    6
    10
    Uveitis
         subjects affected / exposed
    9 / 130 (6.92%)
    6 / 131 (4.58%)
         occurrences all number
    9
    6
    Visual Acuity Reduced
         subjects affected / exposed
    10 / 130 (7.69%)
    6 / 131 (4.58%)
         occurrences all number
    11
    9
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    9 / 130 (6.92%)
    14 / 131 (10.69%)
         occurrences all number
    11
    17
    Injection Site Pain
         subjects affected / exposed
    9 / 130 (6.92%)
    8 / 131 (6.11%)
         occurrences all number
    9
    16
    Pyrexia
         subjects affected / exposed
    8 / 130 (6.15%)
    6 / 131 (4.58%)
         occurrences all number
    8
    7
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    3 / 130 (2.31%)
    9 / 131 (6.87%)
         occurrences all number
    3
    9
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    9 / 130 (6.92%)
    4 / 131 (3.05%)
         occurrences all number
    10
    4
    Nausea
         subjects affected / exposed
    9 / 130 (6.92%)
    4 / 131 (3.05%)
         occurrences all number
    10
    6
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    12 / 130 (9.23%)
    28 / 131 (21.37%)
         occurrences all number
    18
    30
    Back Pain
         subjects affected / exposed
    7 / 130 (5.38%)
    10 / 131 (7.63%)
         occurrences all number
    8
    11
    Pain In Extremity
         subjects affected / exposed
    3 / 130 (2.31%)
    10 / 131 (7.63%)
         occurrences all number
    5
    12
    Infections and infestations
    Influenza
         subjects affected / exposed
    7 / 130 (5.38%)
    3 / 131 (2.29%)
         occurrences all number
    8
    3
    Nasopharyngitis
         subjects affected / exposed
    20 / 130 (15.38%)
    23 / 131 (17.56%)
         occurrences all number
    28
    32
    Sinusitis
         subjects affected / exposed
    4 / 130 (3.08%)
    8 / 131 (6.11%)
         occurrences all number
    11
    12
    Upper Respiratory Tract Infection
         subjects affected / exposed
    3 / 130 (2.31%)
    10 / 131 (7.63%)
         occurrences all number
    4
    10
    Urinary Tract Infection
         subjects affected / exposed
    11 / 130 (8.46%)
    13 / 131 (9.92%)
         occurrences all number
    15
    17

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Mar 2010
    Substantial changes included: ● Revised efficacy variables to reflect updated scientific approach and statistical analyses ● Inclusion Criteria No. 3 and throughout protocol: changed "active" to active "inflammatory" chorioretinal and/or "inflammatory" retinal vascular lesion ● Increase the maximum allowable stable dose for an inactive uveitis patient to include up to 35 mg. ● Exclusion Criteria No. 9: changed BCVA worse than 20/400 to 20/200 and logMar from "> 1.34" to "> 1.0" ● Exclusion Criteria No. 10: added "All subjects with intermediate uveitis must have had a prior brain magnetic resonance imaging (MRI) at time of or after diagnosis of intermediate uveitis" ● Exclusion Criteria No. 14: changed dose of mycophenolate mofetil from ≤ 2 "mg" to ≤ 2 "gm" ● Concomitant Therapy: added text regarding concomitant and prohibited therapies to provide additional clarification regarding the use of topical or systemic corticosteroids ● Japan Sub-study: added active Hepatitis C and positive or indeterminate β-D-glucan as an exclusion criteria ● Japan Sub-study: Analysis of Efficacy: removed the following sentence: "An additional analysis the Time to Treatment Failure will be compared between the adalimumab group and the placebo group in the Japan ITT dataset using a log-rank test" as agreed upon with Japan's Pharmaceuticals and Medical Devices Agency (PMDA), the primary analysis will be performed on the integrated ITT dataset and a statistical test to compare the treatment groups in the Japan ITT dataset is not necessary.
    23 Apr 2010
    Substantial changes included: ● Best Corrected Visual Acuity Testing: Removed the requirement that the individual performing refraction and BCVA testing not be the Principal Investigator or the same person entering data on the eCRFs based on updated visual acuity requirements. ● Handling/Processing of Samples: added "Blood samples for Adalimumab and anti-adalimumab antibody (AAA) analysis will be collected by venipuncture into appropriately labeled evacuated serum collection tubes without gel separator at the required visits. Blood samples for Adalimumab analysis will also be obtained if a subject is discontinued from the study. Sufficient blood will be collected to provide approximately 1 mL serum. Allow the blood to clot for 30 minutes at room temperature before centrifugation." ● Collection of Samples for Analysis: Revised the number of pharmacokinetic (PK) and AAA samples that will be collected.
    10 Jun 2010
    Substantial changes included: ● Inclusion Criterion No. 5 – Revised sentence to read "Subject must have a history of experiencing a disease flare while tapering off their oral corticosteroid therapy within the past 18 months" to provide correct interpretation of the appropriate subject population to be included. ● Efficacy Variables – Removed "3 lines" throughout the protocol when assessing Best Corrected Visual Acuity to provide clarification that worsening of BCVA will be based on the number of letters. ● Added text to indicate that information collected on AC cell count/grade would not only be a component of the primary endpoint but also be evaluated as a secondary efficacy variable. ● Exclusion Criterion No. 2: Added Human T Lymphotropic Virus Type 1 (HTLV-1) infection, Whipple's disease and HZV (herpes zoster virus). ● Prohibited Therapy: Added "anti-vascular endothelial growth factor (VEGF) therapy" and "periocular, intraocular or intravitreal injections."
    11 Feb 2011
    Substantial changes included: Inclusion Criterion: ● Added requirement for ≥10 mg oral prednisone for 90 days prior to Baseline ● Added option to use QuantiFERON®-TB Gold for TB screening ● Removed text requiring reading of purified protein derivative (PPD) test at study site and added text indicating TB screening tests are performed locally and annually ● Added instruction for TB prophylaxis ● Added instruction that subjects with documented completion of Center for Disease Control (CDC) recommended prophylaxis may conditionally be permitted to enroll ● Added increase of screening period up to 45 days if a subject is required to receive ≥ 28 days of TB prophylaxis Exclusion Criteria: ● Exclude subjects with 1 immunosuppressive therapy with dose that has not been stable for at least 28 days or who are on a dose outside of the allowed range listed ● Exclude subjects with macular edema due to diabetic retinopathy ● Changed description of demyelinating disease ● Expanded and clarified description of exclusionary infections ● Clarified that subjects with an active systemic viral infection or any active viral infection are excluded ● Added exclusion criterion that allows the prior use of intravitreal anti-VEGF therapy provided a 3 month washout period from Baseline is observed ● Added Ozurdex® (dexamethasone implant) and intravitreal methotrexate as prohibited therapy ● Exclude marijuana use including medical marijuana in the previous 12 months ● Exclude hepatitis B surface antigen positive subjects ● Removed requirement that Screening visit fundus photo is evaluated prior to the Baseline visit Removed central reader's precedence if assessment differs from investigator's assessment ● Added diagnosis of lupus like syndrome, multiple sclerosis or demyelinating disease and non-compliance with TB therapy as discontinuation criteria ● Added criteria that age-related eye disease study (AREDS) classification does not apply to subjects with pseudophakia
    16 Feb 2011
    Substantial changes included: ● Clarified that methotrexate, cyclosporine, mycophenolate mofetil or azathioprine cannot be discontinued within 28 days prior to the Baseline visit.
    21 Mar 2011
    Substantial Changes included: ● Added text to exclude use of systemic carbonic anhydrase inhibitor within 1 week prior to Screening visit and as prohibited therapy. ● Provided details of the nature of syphilis confirmatory testing. ● Added instruction to evaluate subjects for treatment failure criteria at Unscheduled visits (as applicable) and complete Unscheduled visit activities per the investigator's clinical judgment. ● Added instruction to use the same fundus camera throughout the study per subject.
    24 Aug 2011
    Substantial changes included: ● Changed period of inactive disease and minimum length of time the subject must be taking ≥ 10 mg of oral prednisone to 28 days prior to Baseline ● Removed allowance for subjects with positive TB tests except if a subject received Bacille Calmette-Guérin (BCG) vaccination or has history of an ulcerative reaction to a PPD skin test. If the PPD test is positive, the QuantiFERON®-TB Gold test must be performed. If the QuantiFERON®-TB Gold test is negative, the subject is eligible ● Added to criterion to require an MRI report completed within 90 days prior to Baseline to include a statement that reveals no hint of demyelinating disease such as multiple sclerosis for subjects who have intermediate uveitis or panuveitis that have signs of intermediate uveitis ● Clarified that immunosuppressive therapy including methotrexate, cyclosporine, mycophenolate mofetil or azathioprine should not be discontinued within 28 days prior to Baseline ● Modification to exclude subjects who received Retisert® within 3 years prior to Baseline or had complications related to the device. Added exclusion for those subjects who had Retisert® removed within 90 days prior to Baseline or complications related to device removal • Changed exclusion of subjects with macular edema due to diabetic retinopathy to subjects with clinically significant macular edema due to diabetic retinopathy ● Modified that both Fluorescent Treponemal Antibody (FTA) and Rapid Plasma Reagin (RPR) must be tested, and if positive the subject would be excluded ● Exclude subjects with macular edema as the only sign of uveitis ● Exclude subjects with a history of scleritis • Exclude subjects who require TB Prophylaxis • Added “any TB-prophylaxis therapy” and “Retisert®" to list of prohibited medications ● Dilated Indirect Ophthalmoscopy: Added instruction to record the number of lesions, the location(s), size(s) and whether the lesions are active or inactive with a retinal drawing
    15 Mar 2012
    Substantial changes included: ● Clarified that at least one disease flare must occur within 18 months of Screening and that this flare has to occur during or up to a maximum of 28 days after tapering off the oral corticosteroid therapy. ● Revised language to include subjects with either negative PPD (< 5 mm of induration) or negative QuantiFERON®-TB Gold test (or Interferon-Gamma Release Assay [IGRA] equivalent) as eligible. Only 1 TB test is permitted to allow the subject in the study. Subjects with a repeat indeterminate QuantiFERON®-TB Gold test (or IGRA equivalent) result are not eligible. Added that subjects with "previous" TB are also not eligible for this study. ● Reduced the number of letters a subject must read for BCVA to 20 letters. ● Added tacrolimus as an acceptable concomitant immunosuppressant. ● Created Exclusion to allow prior use of cyclophosphamide provided a 30 day washout prior to Baseline is observed. Added chlorambucil and cyclophosphamide to prohibited concomitant medication list. ● Exclude subjects with cystoid macular edema unless the documented retinal changes are persistent, residual and stable as defined by the SUN criteria (persistent is > 3 months duration). ● Reduced intravitreal anti-VEGF therapy washout periods for Lucentis® (ranibizumab) or Avastin® (bevacizumab) to 45 days of Baseline or for anti-VEGF Trap (Aflibercept) for 60 days of Baseline. ● Changed to allow refractive laser surgery, retinal laser photocoagulation or neodymium-doped yttrium aluminium garnet (Nd:YAG) capsulotomy laser ≥ 30 days prior to Baseline visit.
    21 Dec 2012
    ● Ranked secondary variables. ● Added language and new requirements regarding malignancy in patients who are 30 years old or younger. ● Adverse Event Reporting changed to require non-serious events of malignancy in subjects 30 or younger to be reported to Abbvie within 24 hours of site awareness.
    24 Jun 2013
    Substantial changes included: ● Removed interim analyses and reduced the total number of treatment failures to complete the study. ● Added Rituxan® (rituximab) as prohibited therapy. ● Added subjects with optic neuritis are exclusionary. ● Added Stelara® (ustekinumab), Benlysta® (belimumab), and corticosteroids with the exceptions of protocol specified prednisone taper and the protocol specified corticosteroid eyedrop taper as prohibited medications.
    19 Feb 2014
    Substantial changes included: • Increase the number of Treatment Failures from currently planned 76 to approximately 96 to ensure approximately 80% statistical power.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA