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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44335   clinical trials with a EudraCT protocol, of which   7366   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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, Randomized, Double-Blind Study to Evaluate Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease and Evidence of Mucosal Ulceration

    Summary
    EudraCT number
    		 2013-001746-33
    Trial protocol
    		 DE   BE   IT   SK   NL   ES   DK   AT   FR  
    Global end of trial date
    30 Jan 2020

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Feb 2021
    First version publication date
    05 Feb 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    M14-115
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02065570
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AbbVie
    Sponsor organisation address
    AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6 4UB
    Public contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
    Scientific contact
    Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@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
    30 Jan 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jan 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the efficacy and safety of 2 adalimumab induction regimens in achieving clinical remission (CDAI < 150) at Week 4 and endoscopic response defined as decrease in SES-CD > 50% from Baseline (or for a Baseline SES-CD of 4, at least a 2-point reduction from Baseline) at Week 12, in subjects with moderately to severely active CD and evidence of mucosal ulceration at Baseline.
    Protection of trial subjects
    Subject and/or legal guardian read and understood the information provided about the study and gave written permission.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 May 2014
    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
    Austria: 15
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    Canada: 64
    Country: Number of subjects enrolled
    Czechia: 41
    Country: Number of subjects enrolled
    Denmark: 9
    Country: Number of subjects enrolled
    France: 15
    Country: Number of subjects enrolled
    Germany: 13
    Country: Number of subjects enrolled
    Hungary: 2
    Country: Number of subjects enrolled
    Israel: 35
    Country: Number of subjects enrolled
    Italy: 25
    Country: Number of subjects enrolled
    Netherlands: 19
    Country: Number of subjects enrolled
    Poland: 72
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Slovakia: 1
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    Switzerland: 7
    Country: Number of subjects enrolled
    Ukraine: 29
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    United States: 142
    Worldwide total number of subjects
    514
    EEA total number of subjects
    237
    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)
    499
    From 65 to 84 years
    15
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were randomized in a 3:2 ratio at Baseline to receive a higher induction adalimumab regimen or standard induction adalimumab regimen during the double-blind Induction Study.

    Pre-assignment
    Screening details
    		 At Week 12, participants were re-randomized in a 1:1 ratio to a double-blind exploratory treatment regimen (adalimumab clinically adjusted [CA] regimen or adalimumab therapeutic drug monitoring [TDM] regimen).

    Period 1
    Period 1 title
    Induction Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    All AbbVie personnel with direct oversight of the conduct and management of the trial (with the exception of AbbVie's Drug Supply Management Team) the Investigator, study site personnel and the subject remained blinded to each subject's treatment throughout the blinded period of the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Induction: Standard Induction Dose
    Arm description
    		 Participants randomized to receive blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.
    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
    Subjects assigned to the standard induction regimen received blinded adalimumab 160 mg (4 syringes) at Baseline. Subjects received adalimumab 80 mg (2 syringes) at Week 2. At Week 4, subjects receive adalimumab 40 mg (1 syringe) eow through Week 12.

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects assigned to the standard induction regimen received matching placebo (4 syringes) at Week 1. Subjects received matching placebo (2 syringes) at Week 2 and matching placebo (4 syringes) at Week 3.

    Arm title
    		 Induction: Higher Induction Dose
    Arm description
    		 Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
    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
    Subjects assigned to the higher induction regimen received blinded adalimumab 160 mg (4 syringes) at Baseline, Week 1, Week 2, and Week 3. At Week 4, subjects received 40 mg (1 syringe) eow through Week 12.

    Number of subjects in period 1
    		Induction: Standard Induction Dose Induction: Higher Induction Dose
    Started
    206
    308
    Completed
    192
    287
    Not completed
    14
    21
         Consent withdrawn by subject
    2
    3
         Adverse Event
    5
    12
         Other, not specified
    6
    5
         Lost to follow-up
    1
    1
    Period 2
    Period 2 title
    Maintenance Study
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    All AbbVie personally with direct oversight of the conduct and management of the trial (with the exception of AbbVie's Drug Supply Management Team) the Investigator, study site personnel and the subject remained blinded to each subject's treatment throughout the blinded period of the study.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Maintenance: Clinically Adjusted (CA) Regimen
    Arm description
    		 Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose could be escalated to every week (ew) starting as early as Week 14 and up to Week 54 based on Crohn's Disease Activity Index (CDAI) or high-sensitivity C-reactive protein (hs-CRP) values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.
    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
    The adalimumab dose was be escalated to every week (ew) starting as early as Week 14 if the subject's CDAI was ≥ 220 or hs-CRP ≥ 10 mg/L (using results from the prior or current visit). These subjects were also to be allowed to escalate at unscheduled visits that may occur only on Weeks 16, 18, 22, 24, 30, 32, 36, 38, 44, 46, 50, 52 and 54.

    Arm title
    		 Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
    Arm description
    		 At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM are determined by protocol-established dose adjustment criteria. Doses are determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 receive 40 mg ew.
    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
    Doses will be determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior visit.

    Number of subjects in period 2 [1]
    		Maintenance: Clinically Adjusted (CA) Regimen Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
    Started
    109
    109
    Completed
    87
    90
    Not completed
    22
    19
         Consent withdrawn by subject
    1
    4
         Adverse Event
    -
    8
         Other, not specified
    11
    5
         Adverse Events
    8
    -
         Lost to follow-up
    2
    2
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: All participants who entered the Maintenance Study.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Induction: Standard Induction Dose
    Reporting group description
    		 Participants randomized to receive blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.

    Reporting group title
    Induction: Higher Induction Dose
    Reporting group description
    		 Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.

    Reporting group values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose Total
    Number of subjects
    		 206 308 514
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 36.4 ( 12.79 ) 36.4 ( 13.02 ) -
    Gender categorical
    Units: Subjects
        Female
    		 109 158 267
        Male
    		 97 150 247
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 5 10 15
        Not Hispanic or Latino
    		 0 0 0
        Unknown or Not Reported
    		 201 298 499
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 0 1 1
        Asian
    		 5 6 11
        Black or African American
    		 18 11 29
        White
    		 182 288 470
        More than one race
    		 1 1 2
        Unknown or Not Reported
    		 0 1 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Induction: Standard Induction Dose
    Reporting group description
    		 Participants randomized to receive blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg every other week (eow) starting at Week 4 through Week 12.

    Reporting group title
    Induction: Higher Induction Dose
    Reporting group description
    		 Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.
    Reporting group title
    Maintenance: Clinically Adjusted (CA) Regimen
    Reporting group description
    		 Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose could be escalated to every week (ew) starting as early as Week 14 and up to Week 54 based on Crohn's Disease Activity Index (CDAI) or high-sensitivity C-reactive protein (hs-CRP) values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.

    Reporting group title
    Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
    Reporting group description
    		 At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM are determined by protocol-established dose adjustment criteria. Doses are determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 receive 40 mg ew.

    Primary: Percentage of Participants Who Achieved Clinical Remission at Week 4

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Achieved Clinical Remission at Week 4
    End point description
    Crohn's Disease Activity Index (CDAI) is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Primary
    End point timeframe
    Week 4
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    43.7
    43.5
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.939 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.1
         upper limit
    		 8.8
    Notes
    [1] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Primary: Percentage of Participants With Endoscopic Response at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants With Endoscopic Response at Week 12
    End point description
    Endoscopic response was scored using the Simplified Endoscopic Score for Crohn's Disease (SES-CD). The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score > 50% from Baseline (or for a Baseline SES-CD of 4, at least a 2 point reduction from Baseline) at Week 12. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    39.3
    42.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Higher Induction Dose v Induction: Standard Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.462 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    3.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.3
         upper limit
    		 11.7
    Notes
    [2] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

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

    		 Close Top of page
    End point title
    		 Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [3]
    End point description
    Adverse event (AE): any untoward medical occurrence that does not necessarily have a causal relationship with treatment. The investigator assessed the relationship of each event to the use of study drug (IP) as either probably related, possibly related, probably not related or not related. Serious AE (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. TEAEs: any event that began or worsened in severity after the first dose of study drug in the induction or maintenance study. Events with unknown severity were counted as severe. Events with unknown relationship to study drug were counted as drug-related. Safety Set: all participants who received >= 1 injection of study drug
    End point type
    Primary
    End point timeframe
    From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).
    Notes
    [3] - 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 are presented per protocol.
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose Maintenance: Clinically Adjusted (CA) Regimen Maintenance: Therapeutic Drug Monitoring (TDM) Regimen
    Number of subjects analysed
    206
    308
    109
    109
    Units: participants
        Any TEAE
    133
    185
    77
    76
        TEAE: reasonable possibility of relationship to IP
    54
    75
    29
    33
        Any severe TEAE
    13
    17
    7
    6
        Any SAE
    10
    14
    5
    7
        Any TEAE leading to discontinuation of IP
    8
    13
    8
    9
        Any TEAE leading to death
    0
    0
    0
    0
        Deaths
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12

    		 Close Top of page
    End point title
    		 Percentage of Participants With Sustained Clinical Remission (Per CDAI) at Both Weeks 4 and 12
    End point description
    CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 4 and Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    35.0
    39.0
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.269 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    4.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 12.8
    Notes
    [4] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants Who Achieve Clinical Response at Week 4 and Endoscopic Response at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Achieve Clinical Response at Week 4 and Endoscopic Response at Week 12
    End point description
    Clinical response was scored using CDAI, which assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline. Endoscopic response was scored using the SES-CD, which evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic response was defined as SES-CD total score >50% from Baseline (or for Baseline SES-CD of 4, at least a 2-point reduction from Baseline) at Week 12.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206 [5]
    308 [6]
    Units: percentage of participants
        number (not applicable)
    20.4
    22.1
    Notes
    [5] - Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    [6] - Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Higher Induction Dose v Induction: Standard Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.61 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.1
         upper limit
    		 8.7
    Notes
    [7] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants With Clinical Remission at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants With Clinical Remission at Week 12
    End point description
    Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    51.5
    62.3
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.008 [8]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    11.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.9
         upper limit
    		 19.6
    Notes
    [8] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 12 Among Participants Taking Corticosteroids at Baseline

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Discontinued Corticosteroid Use and Achieved Clinical Remission at Week 12 Among Participants Taking Corticosteroids at Baseline
    End point description
    Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Intent to Treat Population: all participants who were randomized. Participants taking corticosteroids at Baseline.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    100
    153
    Units: percentage of participants
        number (not applicable)
    48.0
    52.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    253
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.336 [9]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.2
         upper limit
    		 18.2
    Notes
    [9] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants With Endoscopic Remission at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants With Endoscopic Remission at Week 12
    End point description
    Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    26.2
    28.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.694 [10]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    1.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 9.1
    Notes
    [10] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Change From Baseline in Fecal Calprotectin Level at Week 4

    		 Close Top of page
    End point title
    		 Change From Baseline in Fecal Calprotectin Level at Week 4
    End point description
    Intent to Treat Population: all participants who were randomized. Participants with a baseline and Week 4 assessment. Observed cases.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    152
    252
    Units: μg/g
        arithmetic mean (standard deviation)
    -1045.7 ( 1648.51 )
    -1157.0 ( 2000.69 )
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    404
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.946
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 LS mean of difference
    Point estimate
    6.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -192.3
         upper limit
    		 205.9

    Secondary: Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 μg/g at Week 4

    		 Close Top of page
    End point title
    		 Percentage of Participants With Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 μg/g at Week 4
    End point description
    Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    27.7
    32.5
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.293 [11]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.5
         upper limit
    		 11.5
    Notes
    [11] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 μg/g at Week 4

    		 Close Top of page
    End point title
    		 Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 μg/g at Week 4
    End point description
    Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    11.2
    14.3
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.304 [12]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 8.6
    Notes
    [12] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 μg/g and Endoscopic Remission at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants With Clinical Remission, Hs-CRP < 5 mg/L and Fecal Calprotectin < 250 μg/g and Endoscopic Remission at Week 12
    End point description
    Clinical remission was scored using the CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Endoscopic remission was scored using the SES-CD.The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy. The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Endoscopic remission was defined as SES-CD ≤ 4 and at least a 2-point reduction versus baseline and no subscore greater than 1 in any individual variable.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206 [13]
    308 [14]
    Units: percentage of participants
        number (not applicable)
    7.3
    11.7
    Notes
    [13] - Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    [14] - Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.092 [15]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    4.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 9.1
    Notes
    [15] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants Who Achieved an SES-CD ≤ 2 at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Achieved an SES-CD ≤ 2 at Week 12
    End point description
    The SES-CD evaluates 4 endoscopic variables (ulcer size ranging from 0 [none] to 3 [very large]; ulcerated surface ranging from 0 [none] to 3 [>30%]; affected surface ranging from 0 [none] to 3 [>75%], and narrowing ranging from 0 [none] to 3 [cannot be passed]) in 5 segments assessed during ileocolonoscopy (ileum, right colon, transverse colon, sigmoid and left colon, and rectum). The total score is the sum of the 4 endoscopic variable scores and range from 0 to 56, where higher scores indicate more severe disease. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    16.0
    20.1
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.322 [16]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 10.2
    Notes
    [16] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants With Clinical Response at Week 4

    		 Close Top of page
    End point title
    		 Percentage of Participants With Clinical Response at Week 4
    End point description
    Clinical response was scored using CDAI is used to assess the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from baseline. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    70.9
    74.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.353 [17]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    3.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.1
         upper limit
    		 11.5
    Notes
    [17] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants With Clinical Response at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants With Clinical Response at Week 12
    End point description
    Clinical response was scored using CDAI. CDAI assesses the symptoms of participants with Crohn's Disease. Scores generally range from 0 to 600, where clinical remission of Crohn's disease is defined as CDAI < 150, and very severe disease is defined as CDAI > 450. Clinical response was defined as a decrease in CDAI ≥ 70 points from Baseline. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    74.8
    83.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.015
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    8.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.8
         upper limit
    		 16

    Secondary: Percentage of Participants Achieving Response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving Response in Inflammatory Bowel Disease Questionnaire (IBDQ) Bowel Symptom Domain at Week 4
    End point description
    The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    71.4
    74.7
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.394 [18]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    3.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 11.1
    Notes
    [18] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 12
    End point description
    The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 8. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    73.3
    76.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose)
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.349 [19]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    3.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 11.2
    Notes
    [19] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Secondary: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 12

    		 Close Top of page
    End point title
    		 Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 12
    End point description
    The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1. Intent to Treat Population: all participants who were randomized. Non-responder imputation.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Induction: Standard Induction Dose Induction: Higher Induction Dose
    Number of subjects analysed
    206
    308
    Units: percentage of participants
        number (not applicable)
    68.4
    76.0
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose)
    Comparison groups
    Induction: Standard Induction Dose v Induction: Higher Induction Dose
    Number of subjects included in analysis
    514
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.054 [20]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Adjusted risk difference
    Point estimate
    7.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 15.3
    Notes
    [20] - Adjusted for previous infliximab use (or prior anti-TNF use for participants randomized under original protocol), hs-CRP at Baseline (<10 mg/L, >=10 mg/L) and Crohn's disease severity at Baseline (CDAI ≤ 300, CDAI > 300).

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug until 70 days following last dose of study drug in the induction study (up to 12 weeks) or maintenance study (up to 56 weeks).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Induction: Higher Induction Dose
    Reporting group description
    		 Participants randomized to receive blinded adalimumab 160 mg at Baseline, Week 1, Week 2, and Week 3. At Week 4, participants receive adalimumab 40 mg eow through Week 12.

    Reporting group title
    Induction: Standard Induction Dose
    Reporting group description
    		 Participants randomized to receive received blinded adalimumab 160 mg at Baseline and matching placebo at Week 1, adalimumab 80 mg and matching placebo at Week 2, matching placebo at Week 3, and then adalimumab 40 mg eow starting at Week 4 through Week 12.

    Reporting group title
    Maintenance: Clinically Adjusted (CA) Regimen
    Reporting group description
    		 Participants randomized to the CA regimen receive adalimumab 40 mg eow beginning at Week 12. The adalimumab dose will be escalated to ew starting as early as Week 14 and up to Week 54 based on CDAI or hs-CRP values, using results from the prior or current study visit. Once participants in the CA regimen are escalated, they remain on adalimumab 40 mg ew dosing.

    Reporting group title
    Maintenance: Therapeutic Drug Management (TDM) Regimen
    Reporting group description
    		 At Weeks 14, 28 and 42, the adalimumab dose for participants randomized to the TDM are determined by protocol-established dose adjustment criteria. Doses are determined using blinded serum concentrations at the prior visit (Weeks 12, 26 and 40, respectively) as well as the CDAI or hs-CRP values from the current or prior study visit. Participants who meet criteria for dose escalation at Weeks 14, 28 or 42 receive 40 mg ew.

    Serious adverse events
    		 Induction: Higher Induction Dose Induction: Standard Induction Dose Maintenance: Clinically Adjusted (CA) Regimen Maintenance: Therapeutic Drug Management (TDM) Regimen
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 308 (4.55%)
    10 / 206 (4.85%)
    5 / 109 (4.59%)
    7 / 109 (6.42%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    PAPILLARY RENAL CELL CARCINOMA
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    CLAVICLE FRACTURE
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HIP FRACTURE
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    1 / 109 (0.92%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    RADIUS FRACTURE
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    1 / 109 (0.92%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    TRAUMATIC LIVER INJURY
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    1 / 109 (0.92%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    SELECTIVE ABORTION
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    AMNESIA
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CEREBRAL INFARCTION
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    SCLERITIS
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    UVEITIS
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 308 (0.32%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CROHN'S DISEASE
         subjects affected / exposed
    3 / 308 (0.97%)
    3 / 206 (1.46%)
    2 / 109 (1.83%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    FAECALOMA
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    GASTROINTESTINAL INFLAMMATION
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL HAEMORRHAGE
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    2 / 308 (0.65%)
    0 / 206 (0.00%)
    1 / 109 (0.92%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    LARGE INTESTINAL STENOSIS
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    1 / 109 (0.92%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUBILEUS
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DRUG ERUPTION
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SUICIDAL IDEATION
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    HYDRONEPHROSIS
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    BACK PAIN
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    ABDOMINAL ABSCESS
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ABSCESS LIMB
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    ACQUIRED IMMUNODEFICIENCY SYNDROME
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INFECTIOUS MONONUCLEOSIS
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    INTESTINAL TUBERCULOSIS
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMOCYSTIS JIROVECII PNEUMONIA
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 308 (0.32%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    VARICELLA
         subjects affected / exposed
    0 / 308 (0.00%)
    0 / 206 (0.00%)
    0 / 109 (0.00%)
    1 / 109 (0.92%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    HYPOKALAEMIA
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    HYPOVOLAEMIA
         subjects affected / exposed
    0 / 308 (0.00%)
    1 / 206 (0.49%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Induction: Higher Induction Dose Induction: Standard Induction Dose Maintenance: Clinically Adjusted (CA) Regimen Maintenance: Therapeutic Drug Management (TDM) Regimen
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    58 / 308 (18.83%)
    54 / 206 (26.21%)
    41 / 109 (37.61%)
    33 / 109 (30.28%)
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    2 / 308 (0.65%)
    11 / 206 (5.34%)
    0 / 109 (0.00%)
    0 / 109 (0.00%)
         occurrences all number
    2
    13
    0
    0
    HEADACHE
         subjects affected / exposed
    17 / 308 (5.52%)
    18 / 206 (8.74%)
    9 / 109 (8.26%)
    8 / 109 (7.34%)
         occurrences all number
    19
    24
    9
    18
    Gastrointestinal disorders
    CROHN'S DISEASE
         subjects affected / exposed
    14 / 308 (4.55%)
    12 / 206 (5.83%)
    16 / 109 (14.68%)
    15 / 109 (13.76%)
         occurrences all number
    15
    14
    20
    17
    DIARRHOEA
         subjects affected / exposed
    2 / 308 (0.65%)
    3 / 206 (1.46%)
    6 / 109 (5.50%)
    4 / 109 (3.67%)
         occurrences all number
    2
    3
    7
    4
    NAUSEA
         subjects affected / exposed
    9 / 308 (2.92%)
    15 / 206 (7.28%)
    5 / 109 (4.59%)
    3 / 109 (2.75%)
         occurrences all number
    10
    17
    7
    3
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    10 / 308 (3.25%)
    16 / 206 (7.77%)
    8 / 109 (7.34%)
    4 / 109 (3.67%)
         occurrences all number
    10
    19
    8
    5
    Infections and infestations
    NASOPHARYNGITIS
         subjects affected / exposed
    19 / 308 (6.17%)
    9 / 206 (4.37%)
    15 / 109 (13.76%)
    10 / 109 (9.17%)
         occurrences all number
    21
    11
    15
    12

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 May 2014
    Major changes included: ○ Clarification as to when corticosteroid therapy dose adjustment may occur. ○ Updated inclusion criterion 2 to clarify that biopsy results consistent with diagnosis of CD, are to be available at the time of inclusion. ○ Updated inclusion criterion 4 to clarify that, per the investigator, the subject had CDAI ≥ 220 and ≤ 450 despite adequate treatment. ○ Updated inclusion criterion 7 to clarify appropriate and approved forms of contraception. ○ Inclusion criterion 12 updated with additional biologic medications that subject cannot be exposed to previously. ○ Updated to Secondary Variables and Additional Variables to revise the order of ranked secondary endpoints and to add new endpoints assessing hospitalization, extra-intestinal manifestation (EIM), and achievement of both symptomatic remission and endoscopic improvement. ○ Blinding of investigational product updated to clarify that if subject safety is of concern, contact to the Study-Designated Physician is not required. ○ AE Collection Period updated to clarify definition of end of trial, and to clarify that all AEs collected during 70-day follow-up period will be captured in the clinical database. ○ Analyzable population updated to clarify the definition of intent-to-treat (ITT) subjects. ○ Primary Efficacy Variable updated with an additional analysis and the appropriateness for Cochran-Mantel-Haenszel (CMH) test was addressed. ○ Language in Subject Information and Consent updated regarding incentives, provisions on treatment/compensating subjects harmed during study which follows new protocol template.
    21 May 2015
    Major changes included: ○ Allowed video recorded endoscopies performed within 45 days of Baseline to be sent for central review for inclusion into the study as long as elements noted are met. ○ Modified the inclusion criterion 3 for SES-CD total score and eliminated the ulceration subscore of 2 or 3 to allow broader enrollment of patients, including those with CD limited to the ileum, as these individuals with moderate to severe CD and a substantial burden of mucosal inflammation are appropriate candidates for this trial. ○ Modified the co-primary and secondary variables as a result of the modified SES-CD entry criteria. ○ Modified inclusion criterion 4 to clarify what 6-TGN level is considered adequate in thiopurine dosing. ○ Correction added that cyclosporine, tacrolimus, or mycophenolate mofetil are prohibited within 60 days prior to baseline. ○ Ensured appropriate endpoints are analyzed and in the correct order of importance based on Agency request. ○ Implemented the collection of Product Quality Complaints. ○ Added language to explain sensitivity analysis that may be done on a certain set of subjects. ○ Added language on imputation methods that will be used in sensitivity analysis. ○ Added a subgroup Region (US, ex US) to be analyzed based on Agency feedback.
    14 Dec 2015
    Major changes included: ○ Clarification of procedures for corticosteroid taper at Week 4. ○ Clarification regarding inclusion criterion 4 and required 6-TGN levels. ○ Clarification that PK testing is to remain blinded and local PK testing should not be performed. ○ Explained that adjudication will be triggered for endoscopy screening timepoints, prior to eligibility reporting, when the central reviewers do not agree on whether or not a subject meets the eligibility criteria. ○ Updated language regarding AE reporting and the 24-hour AbbVie Medical Escalation Hotline.
    28 Mar 2016
    Major changes included: ○ Language for the induction study and new maintenance study; added a 44-week DB maintenance study to follow with 2 study drug arms, one using TDM and the other using clinical assessment. ○ Added a new ranked secondary endpoint following International Organization for the Study of Inflammatory Bowel Disease (IOIBD) expert recommendation, and the addition of 300 subjects. ○ Removal of language regarding the ability to roll into extension Study M14-347. ○ Clarified how the sample size is being calculated as a result of the increased number of subjects and the addition of the secondary endpoint. ○ Clarified how secondary endpoint number 4 will be compared and added the endpoint regarding subject who achieve SES-CD ≤ 2 at Week 12 per IOIBD recommendation. ○ Explained that the PK concentration levels determined for the TDM regimen were based on 2 concentration thresholds in conjunction with clinical response criteria as expected to occur in clinical setting. ○ Identified changes in the efficacy endpoints in the induction study as well as added all new efficacy endpoints for the maintenance study.
    20 Mar 2017
    Major changes included: ○ Clarified that low-dose aspirin for prevention of heart attacks, unstable angina, or transient ischemic attacks is acceptable to use prior to and during the study. ○ Clarified when an endoscopy is required for subjects that prematurely discontinue.
    27 Nov 2018
    Major changes included: ○ Sample size was updated based on adequacy of power assumed for updated endoscopic co-primary variable. ○ Update to endoscopic co-primary variable. ○ Updated secondary and exploratory maintenance endpoints to reflect change in primary endoscopic endpoint. ○ Modified ranked secondary endpoint #13 and #14 to focus on evaluation of bowel symptom domain of Inflammatory Bowel Disease Questionnaire (IBDQ) that is directly related to the disease and relevant to IBD patients. ○ Added ranked secondary endpoint #15 to include fatigue in the evaluation as it is considered relevant to IBD patients and may provide information complimentary to the primary endpoint. ○ Added and modified non-ranked secondary endpoints to examine the effect of treatment on various aspects of patients' life as measured by IBDQ total score and domain scores, as well as the fatigue item in IBDQ. ○ Modified non-ranked efficacy endpoint definition for symptomatic remission and response to align with current AbbVie IBD registrational trials. ○ Added additional non-ranked efficacy endpoints at Week 56 to assess the effect of dose escalation. ○ Added information to describe Interim Analysis which may be performed via a database cut.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 09 16:10:50 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA