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    Clinical Trial Results:
    A Phase 2, open-label, multicenter study to assess the safety and efficacy of certolizumab pegol in children and adolescents with active Crohn’s disease (NURTURE Study)

    Summary
    EudraCT number
    2014-004381-24
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    02 Jul 2012

    Results information
    Results version number
    v1(current)
    This version publication date
    30 Jun 2016
    First version publication date
    10 Jul 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    C87035
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00899678
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UCB Celltech
    Sponsor organisation address
    208 Bath Road, Slough, United Kingdom, SL1 3 WE
    Public contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 4815 15, clinicaltrials@ucb.com
    Scientific contact
    Clinical Trial Registries and Results Disclosure, UCB BIOSCIENCES GmbH, +49 2173 48 15 15, clinicaltrials@ucb.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    08 Oct 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jul 2012
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to assess the efficacy of certolizumab pegol in children and adolescents with moderately to severely active Crohn’s disease (CD). This study also assesses certolizumab pegol treatment in this population with respect to: - Safety - Tolerability - Efficacy (secondary efficacy variables, including the impact upon growth and development) - Immunogenicity - Pharmacokinetics - Subject-reported outcomes
    Protection of trial subjects
    Not applicable
    Background therapy
    Corticosteroids at screening were tapered according to a schedule between Week 2 and Week 8. In the event of a flare in Crohn’s disease, corticosteroids could be reintroduced at the same dose as at Week 0.
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    01 Jun 2009
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    4 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Canada: 23
    Country: Number of subjects enrolled
    New Zealand: 5
    Country: Number of subjects enrolled
    United States: 67
    Worldwide total number of subjects
    99
    EEA total number of subjects
    0
    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)
    23
    Adolescents (12-17 years)
    76
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The Participant Flow refers to the Safety Set (SS) population. The Safety Population includes all subjects enrolled who received at least 1 injection of study treatment.

    Pre-assignment
    Screening details
    During an Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W). Subjects who showed a clinical response at Week 6 were randomized in a 1:1 ratio to one of 2 dose groups. Subjects who did not respond at Week 6 were withdrawn from the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Induction Only
    Arm description
    Induction Only is the period between the Week 0 dose and prior to first maintenance dose (Week 8). Induction Only includes all subjects who received a dose during the Induction Period but did not receive any treatment during the Maintenance Period. During the Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W) (for a total of 3 administrations of drug) at a dose of either: - 400 mg for subjects ≥ 40 kg - 200 mg for subjects 20 to < 40 kg
    Arm type
    Experimental

    Investigational medicinal product name
    Certolizumab Pegol
    Investigational medicinal product code
    Certolizumab Pegol
    Other name
    Cimzia
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Maintenance High-Dose group: 400 mg Certolizumab Pegol for subjects ≥ 40 kg or 200 mg Certolizumab Pegol for subjects 20 to < 40 kg Maintenance Low-Dose Maintenance Low-Dose group: 200 mg Certolizumab Pegol for subjects ≥ 40 kg or 100 mg Certolizumab Pegol for subjects 20 to < 40 kg

    Arm title
    Maintenance Low-Dose
    Arm description
    Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg
    Arm type
    Experimental

    Investigational medicinal product name
    Certolizumab Pegol
    Investigational medicinal product code
    Certolizumab Pegol
    Other name
    Cimzia
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Maintenance High-Dose group: 400 mg Certolizumab Pegol for subjects ≥ 40 kg or 200 mg Certolizumab Pegol for subjects 20 to < 40 kg Maintenance Low-Dose Maintenance Low-Dose group: 200 mg Certolizumab Pegol for subjects ≥ 40 kg or 100 mg Certolizumab Pegol for subjects 20 to < 40 kg

    Arm title
    Maintenance High-Dose
    Arm description
    Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg
    Arm type
    Experimental

    Investigational medicinal product name
    Certolizumab Pegol
    Investigational medicinal product code
    Certolizumab Pegol
    Other name
    Cimzia
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Maintenance High-Dose group: 400 mg Certolizumab Pegol for subjects ≥ 40 kg or 200 mg Certolizumab Pegol for subjects 20 to < 40 kg Maintenance Low-Dose Maintenance Low-Dose group: 200 mg Certolizumab Pegol for subjects ≥ 40 kg or 100 mg Certolizumab Pegol for subjects 20 to < 40 kg

    Number of subjects in period 1
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Started
    27
    37
    35
    Completed
    2
    12
    7
    Not completed
    25
    25
    28
         Protocol deviation
    1
    1
    1
         Other
    1
    2
    2
         Lack of efficacy
    17
    11
    18
         SAE, non-fatal
    3
    5
    2
         AE, unknown
    -
    1
    -
         Consent withdrawn by subject
    -
    1
    2
         AE, non-serious non-fatal
    3
    4
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Induction Only
    Reporting group description
    Induction Only is the period between the Week 0 dose and prior to first maintenance dose (Week 8). Induction Only includes all subjects who received a dose during the Induction Period but did not receive any treatment during the Maintenance Period. During the Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W) (for a total of 3 administrations of drug) at a dose of either: - 400 mg for subjects ≥ 40 kg - 200 mg for subjects 20 to < 40 kg

    Reporting group title
    Maintenance Low-Dose
    Reporting group description
    Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg

    Reporting group title
    Maintenance High-Dose
    Reporting group description
    Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg

    Reporting group values
    Induction Only Maintenance Low-Dose Maintenance High-Dose Total
    Number of subjects
    27 37 35 99
    Age categorical
    Units: Subjects
        6-11 years
    6 9 8 23
        12-17 years
    21 28 27 76
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    13.8 ± 2.67 13.2 ± 2.41 13.4 ± 2.46 -
    Gender Categorical
    Units: Subjects
        Female
    10 10 21 41
        Male
    17 27 14 58
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian / Alaskan Native
    0 0 0 0
        Asian
    1 0 0 1
        Black
    3 3 8 14
        Native Hawaiian or other Pacific islander
    0 0 0 0
        White
    22 32 27 81
        Other / Mixed
    1 2 0 3
    Weight
    Units: kilogram
        arithmetic mean (standard deviation)
    46.5 ± 12.565 45.67 ± 14.638 50.35 ± 18.569 -
    Height
    Units: centimeter
        arithmetic mean (standard deviation)
    157.46 ± 13.841 155.32 ± 13.589 157.22 ± 13.32 -
    Body Mass Index (BMI)
    Units: kilogram per square meter
        arithmetic mean (standard deviation)
    18.39 ± 2.504 18.51 ± 3.531 19.79 ± 4.897 -
    Body Surface Area (BSA)
    Units: square meter
        arithmetic mean (standard deviation)
    1.42 ± 0.25 1.39 ± 0.272 1.47 ± 0.319 -

    End points

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    End points reporting groups
    Reporting group title
    Induction Only
    Reporting group description
    Induction Only is the period between the Week 0 dose and prior to first maintenance dose (Week 8). Induction Only includes all subjects who received a dose during the Induction Period but did not receive any treatment during the Maintenance Period. During the Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W) (for a total of 3 administrations of drug) at a dose of either: - 400 mg for subjects ≥ 40 kg - 200 mg for subjects 20 to < 40 kg

    Reporting group title
    Maintenance Low-Dose
    Reporting group description
    Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg

    Reporting group title
    Maintenance High-Dose
    Reporting group description
    Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg

    Primary: Percentage of subjects in clinical remission at Week 62

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    End point title
    Percentage of subjects in clinical remission at Week 62 [1]
    End point description
    Clinical remission is defined as a Pediatric Crohn’s Disease Activity Index (PCDAI) score ≤ 10. The Pediatric Crohn’s Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity.
    End point type
    Primary
    End point timeframe
    Week 62
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized in tables as descriptive statistics only.
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [2]
    37
    35
    Units: percentage of participants
    number (confidence interval 95%)
        number (95 % CI)
    ( to )
    24.3 (10.5 to 38.1)
    17.1 (4.7 to 29.6)
    Notes
    [2] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Absolute Pediatric Crohn’s Disease Activity Index (PCDAI) scores at Week 62

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    End point title
    Absolute Pediatric Crohn’s Disease Activity Index (PCDAI) scores at Week 62
    End point description
    The Pediatric Crohn’s Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity.
    End point type
    Secondary
    End point timeframe
    Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [3]
    11
    7
    Units: Score on a scale
    arithmetic mean (standard deviation)
        mean (standard deviation)
    ±
    8.18 ± 6.9
    7.14 ± 7.83
    Notes
    [3] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Change in Pediatric Crohn's Disease Activity Index (PCDAI) scores from Week 0 to the end of the study (Week 62)

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    End point title
    Change in Pediatric Crohn's Disease Activity Index (PCDAI) scores from Week 0 to the end of the study (Week 62)
    End point description
    The Pediatric Crohn's Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity. A negative value in change from Baseline indicates an improvement from Baseline to Week 62.
    End point type
    Secondary
    End point timeframe
    From Week 0 to Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [4]
    11
    7
    Units: units on a scale
    arithmetic mean (standard deviation)
        mean (standard deviation)
    ±
    -29.77 ± 8.097
    -27.14 ± 5.669
    Notes
    [4] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Percentage of subjects achieving clinical response from Week 0 to the end of the study (Week 62)

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    End point title
    Percentage of subjects achieving clinical response from Week 0 to the end of the study (Week 62)
    End point description
    Clinical response is defined as a decrease from Week 0 in Pediatric Crohn’s Disease Activity Index (PCDAI) score of ≥ 15 points and a total PCDAI score ≤ 30 points. The Pediatric Crohn’s Disease Activity Index (PCDAI) consists of 4 domains (laboratory, height/weight, examination, and history) with several assessments that are converted into a PCDAI score which can range from 0 to 100 points, with a higher score indicating more severe disease activity.
    End point type
    Secondary
    End point timeframe
    From Week 0 to Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [5]
    37
    35
    Units: percentage of participants
    number (confidence interval 95%)
        number (95 % CI)
    ( to )
    29.7 (15 to 44.5)
    20 (6.7 to 33.3)
    Notes
    [5] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: C-Reactive Protein (CRP) levels at Week 62

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    End point title
    C-Reactive Protein (CRP) levels at Week 62
    End point description
    The C-Reactive Protein (CRP) is a considered marker of inflammation in subjects with Crohn’s Disease (CD)
    End point type
    Secondary
    End point timeframe
    Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [6]
    11
    7
    Units: mg/L
    geometric mean (confidence interval 95%)
        geometric mean (95 % CI)
    ( to )
    7.2 (2.5 to 20.7)
    5.8 (2.1 to 15.7)
    Notes
    [6] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Change in C-Reactive Protein (CRP) levels from Week 0 to the end of the study (Week 62)

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    End point title
    Change in C-Reactive Protein (CRP) levels from Week 0 to the end of the study (Week 62)
    End point description
    The C-Reactive Protein (CRP) is a considered marker of inflammation in subjects with Crohn’s Disease (CD). Changes from Baseline in CRP levels are expressed as a ratio with the value measured at Baseline as the denominator.
    End point type
    Secondary
    End point timeframe
    From Week 0 to Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [7]
    11
    7
    Units: ratio
    geometric mean (confidence interval 95%)
        geometric mean (95 % CI)
    ( to )
    0.49 (0.17 to 1.41)
    1.84 (0.27 to 12.71)
    Notes
    [7] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Erythrocyte Sedimentation Rate (ESR) at Week 62

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    End point title
    Erythrocyte Sedimentation Rate (ESR) at Week 62
    End point description
    The Erythrocyte Sedimentation Rate (ESR) is a considered biomarker of inflammation in subjects with Crohn’s Disease (CD).
    End point type
    Secondary
    End point timeframe
    Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [8]
    12
    7
    Units: mm/h
    geometric mean (confidence interval 95%)
        geometric mean (95 % CI)
    ( to )
    20.9 (11.8 to 37.2)
    25.2 (12.3 to 51.7)
    Notes
    [8] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Change in Erythrocyte Sedimentation Rate (ESR) from Week 0 to the end of the study (Week 62)

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    End point title
    Change in Erythrocyte Sedimentation Rate (ESR) from Week 0 to the end of the study (Week 62)
    End point description
    The Erythrocyte Sedimentation Rate (ESR) is a considered biomarker of inflammation in subjects with Crohn’s Disease (CD). Changes from Baseline in CRP levels are expressed as a ratio with the value measured at baseline as the denominator.
    End point type
    Secondary
    End point timeframe
    From Week 0 to Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [9]
    12
    7
    Units: ratio
    geometric mean (confidence interval 95%)
        geometric mean (95 % CI)
    ( to )
    0.57 (0.31 to 1.04)
    1.08 (0.39 to 3.02)
    Notes
    [9] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Change in growth scores (Tanner stage [assessing puberty]) from Week 0 to the end of the study (Week 62)

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    End point title
    Change in growth scores (Tanner stage [assessing puberty]) from Week 0 to the end of the study (Week 62)
    End point description
    The Tanner stage is an assessment of developmental stage on external genitalia and pubic hair (boys), and on breast and pubic hair (girls). Values range from 1 to 5 where a higher number indicates more development.
    End point type
    Secondary
    End point timeframe
    From Week 0 to Week 62
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [10]
    10
    7
    Units: participants
        Increase from Stage I to Stage II
    2
    0
        Increase from Stage I to Stage III
    1
    1
        Increase from Stage II to Stage III
    0
    1
        Increase from Stage III to Stage IV
    2
    0
        Increase from Stage IV to Stage V
    0
    1
        Decrease from Stage IV to Stage III
    1
    1
        Subjects remained in Stage I
    0
    1
        Subjects remained in Stage III
    0
    2
        Subjects remained in Stage IV
    1
    0
        Subjects remained in Stage V
    3
    0
    Notes
    [10] - Subjects from "Induction Only" were not included in the Analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Percentage of subjects who initiated steroid tapering

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    End point title
    Percentage of subjects who initiated steroid tapering
    End point description
    Subjects receiving corticosteroids at Screening may start a defined tapering schedule between Weeks 2 and 8. Corticosteroid tapering must start at the latest by Week 8. Corticosteroid doses are tapered at different rates depending on the subject’s dose.
    End point type
    Secondary
    End point timeframe
    From Week 2 up to Week 8
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [11]
    21
    20
    Units: percentage of subjects
    number (confidence interval 95%)
        number (95 % CI)
    ( to )
    71.4 (52.1 to 90.8)
    65 (44.1 to 85.9)
    Notes
    [11] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Secondary: Percentage of subjects in corticosteroid-free remission at the end of the study

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    End point title
    Percentage of subjects in corticosteroid-free remission at the end of the study
    End point description
    Corticosteroid use at end of study is defined as 84 days past the last dose of study medication. Remission is assessed at the last visit where Pediatric Crohn’s Disease Activity index (PCDAI) data is available.
    End point type
    Secondary
    End point timeframe
    Last/Withdrawal Visit (up to Week 62)
    End point values
    Induction Only Maintenance Low-Dose Maintenance High-Dose
    Number of subjects analysed
    0 [12]
    21
    20
    Units: percentage of paticipants
    number (confidence interval 95%)
        number (95 % CI)
    ( to )
    23.8 (5.6 to 42)
    15 (0 to 30.6)
    Notes
    [12] - Subjects from "Induction Only" were not included in the analysis of this End Point.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events (AEs) were collected over 68 weeks (from Week -6 to Week 62).
    Adverse event reporting additional description
    Adverse Events (AEs) refer to the Safety Set (SS) population. All subjects in the Safety Population (n=99) participated in the Induction Period. There were 27 subjects who did not continue into the Maintenance Period.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    15.0
    Reporting groups
    Reporting group title
    Induction Period
    Reporting group description
    Induction Only is the period between the Week 0 dose and prior to first maintenance dose (Week 8). Induction Only includes all subjects who received a dose during the Induction Period but did not receive any treatment during the Maintenance Period. During the Induction Period (Weeks 0 to 6), subjects were administered Certolizumab Pegol (CZP) subcutaneously every 2 weeks (Q2W) (for a total of 3 administrations of drug) at a dose of either: - 400 mg for subjects ≥ 40 kg - 200 mg for subjects 20 to < 40 kg

    Reporting group title
    Maintenance Low-Dose
    Reporting group description
    Maintenance Low-Dose group*: 200 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 100 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg

    Reporting group title
    Overall Study
    Reporting group description
    Overall Study comprises Induction Period and Maintenance Period (Week -6 to Week 62).

    Reporting group title
    Maintenance High-Dose
    Reporting group description
    Maintenance High-Dose group*: 400 mg Certolizumab Pegol once every 4 weeks for subjects ≥ 40 kg or 200 mg Certolizumab Pegol once every 4 weeks for subjects 20 to < 40 kg *prior to this dosing regimen, subjects underwent an induction of Certolizumab Pegol administered subcutaneously every 2 weeks (total 3 injections) at of either 400 mg for subjects ≥ 40 kg or 200 mg for subjects 20 to < 40 kg

    Serious adverse events
    Induction Period Maintenance Low-Dose Overall Study Maintenance High-Dose
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 99 (6.06%)
    4 / 37 (10.81%)
    14 / 99 (14.14%)
    4 / 35 (11.43%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Investigations
    Weight decreased
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    0 / 35 (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
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    1 / 99 (1.01%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    1 / 99 (1.01%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    1 / 99 (1.01%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    0 / 35 (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
    Diarrhoea
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    1 / 99 (1.01%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 37 (0.00%)
    2 / 99 (2.02%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    0 / 35 (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
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    0 / 35 (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
    Infections and infestations
    Candidiasis
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    1 / 99 (1.01%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    2 / 99 (2.02%)
    0 / 37 (0.00%)
    2 / 99 (2.02%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    1 / 99 (1.01%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Salmonellosis
         subjects affected / exposed
    1 / 99 (1.01%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    0 / 35 (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
    Viral infection
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 37 (0.00%)
    1 / 99 (1.01%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perineal abscess
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    1 / 99 (1.01%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    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 Period Maintenance Low-Dose Overall Study Maintenance High-Dose
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    59 / 99 (59.60%)
    28 / 37 (75.68%)
    78 / 99 (78.79%)
    27 / 35 (77.14%)
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 99 (0.00%)
    2 / 37 (5.41%)
    2 / 99 (2.02%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Ligament sprain
         subjects affected / exposed
    0 / 99 (0.00%)
    2 / 37 (5.41%)
    2 / 99 (2.02%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 37 (0.00%)
    2 / 99 (2.02%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    2
    Weight decreased
         subjects affected / exposed
    2 / 99 (2.02%)
    2 / 37 (5.41%)
    4 / 99 (4.04%)
    1 / 35 (2.86%)
         occurrences all number
    2
    2
    7
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    5 / 99 (5.05%)
    3 / 37 (8.11%)
    8 / 99 (8.08%)
    2 / 35 (5.71%)
         occurrences all number
    5
    3
    13
    5
    Oropharyngeal pain
         subjects affected / exposed
    5 / 99 (5.05%)
    2 / 37 (5.41%)
    8 / 99 (8.08%)
    2 / 35 (5.71%)
         occurrences all number
    5
    2
    9
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 99 (0.00%)
    1 / 37 (2.70%)
    3 / 99 (3.03%)
    2 / 35 (5.71%)
         occurrences all number
    0
    1
    3
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    9 / 99 (9.09%)
    4 / 37 (10.81%)
    12 / 99 (12.12%)
    3 / 35 (8.57%)
         occurrences all number
    12
    10
    26
    4
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    3 / 99 (3.03%)
    3 / 37 (8.11%)
    6 / 99 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    3
    4
    7
    0
    Injection site pain
         subjects affected / exposed
    22 / 99 (22.22%)
    4 / 37 (10.81%)
    22 / 99 (22.22%)
    6 / 35 (17.14%)
         occurrences all number
    55
    17
    108
    36
    Pyrexia
         subjects affected / exposed
    9 / 99 (9.09%)
    6 / 37 (16.22%)
    20 / 99 (20.20%)
    9 / 35 (25.71%)
         occurrences all number
    15
    7
    31
    9
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 99 (4.04%)
    3 / 37 (8.11%)
    10 / 99 (10.10%)
    4 / 35 (11.43%)
         occurrences all number
    4
    4
    12
    4
    Abdominal pain upper
         subjects affected / exposed
    4 / 99 (4.04%)
    5 / 37 (13.51%)
    9 / 99 (9.09%)
    2 / 35 (5.71%)
         occurrences all number
    4
    5
    12
    3
    Anal inflammation
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 37 (0.00%)
    2 / 99 (2.02%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    2
    Constipation
         subjects affected / exposed
    3 / 99 (3.03%)
    3 / 37 (8.11%)
    7 / 99 (7.07%)
    1 / 35 (2.86%)
         occurrences all number
    3
    3
    7
    1
    Crohn's disease
         subjects affected / exposed
    0 / 99 (0.00%)
    5 / 37 (13.51%)
    12 / 99 (12.12%)
    7 / 35 (20.00%)
         occurrences all number
    0
    7
    15
    8
    Diarrhoea
         subjects affected / exposed
    7 / 99 (7.07%)
    3 / 37 (8.11%)
    12 / 99 (12.12%)
    3 / 35 (8.57%)
         occurrences all number
    7
    5
    19
    7
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 99 (2.02%)
    2 / 37 (5.41%)
    5 / 99 (5.05%)
    2 / 35 (5.71%)
         occurrences all number
    2
    2
    6
    2
    Mouth ulceration
         subjects affected / exposed
    2 / 99 (2.02%)
    3 / 37 (8.11%)
    8 / 99 (8.08%)
    3 / 35 (8.57%)
         occurrences all number
    2
    3
    8
    3
    Nausea
         subjects affected / exposed
    6 / 99 (6.06%)
    3 / 37 (8.11%)
    10 / 99 (10.10%)
    2 / 35 (5.71%)
         occurrences all number
    8
    3
    13
    2
    Stomatitis
         subjects affected / exposed
    2 / 99 (2.02%)
    1 / 37 (2.70%)
    5 / 99 (5.05%)
    2 / 35 (5.71%)
         occurrences all number
    3
    1
    6
    2
    Toothache
         subjects affected / exposed
    1 / 99 (1.01%)
    3 / 37 (8.11%)
    3 / 99 (3.03%)
    0 / 35 (0.00%)
         occurrences all number
    1
    3
    4
    0
    Vomiting
         subjects affected / exposed
    6 / 99 (6.06%)
    3 / 37 (8.11%)
    13 / 99 (13.13%)
    6 / 35 (17.14%)
         occurrences all number
    7
    3
    20
    10
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    3 / 99 (3.03%)
    1 / 37 (2.70%)
    5 / 99 (5.05%)
    1 / 35 (2.86%)
         occurrences all number
    3
    1
    5
    1
    Rash
         subjects affected / exposed
    2 / 99 (2.02%)
    3 / 37 (8.11%)
    5 / 99 (5.05%)
    0 / 35 (0.00%)
         occurrences all number
    2
    6
    8
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    6 / 99 (6.06%)
    4 / 37 (10.81%)
    12 / 99 (12.12%)
    2 / 35 (5.71%)
         occurrences all number
    7
    4
    13
    2
    Myalgia
         subjects affected / exposed
    0 / 99 (0.00%)
    2 / 37 (5.41%)
    2 / 99 (2.02%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    4 / 99 (4.04%)
    3 / 37 (8.11%)
    8 / 99 (8.08%)
    1 / 35 (2.86%)
         occurrences all number
    4
    3
    8
    1
    Infections and infestations
    Ear infection
         subjects affected / exposed
    1 / 99 (1.01%)
    2 / 37 (5.41%)
    4 / 99 (4.04%)
    1 / 35 (2.86%)
         occurrences all number
    1
    2
    4
    1
    Influenza
         subjects affected / exposed
    1 / 99 (1.01%)
    3 / 37 (8.11%)
    6 / 99 (6.06%)
    2 / 35 (5.71%)
         occurrences all number
    1
    3
    7
    3
    Nasopharyngitis
         subjects affected / exposed
    5 / 99 (5.05%)
    1 / 37 (2.70%)
    8 / 99 (8.08%)
    2 / 35 (5.71%)
         occurrences all number
    5
    1
    8
    2
    Pharyngitis
         subjects affected / exposed
    1 / 99 (1.01%)
    2 / 37 (5.41%)
    3 / 99 (3.03%)
    0 / 35 (0.00%)
         occurrences all number
    1
    2
    3
    0
    Sinusitis
         subjects affected / exposed
    2 / 99 (2.02%)
    3 / 37 (8.11%)
    5 / 99 (5.05%)
    1 / 35 (2.86%)
         occurrences all number
    2
    3
    6
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 99 (0.00%)
    8 / 37 (21.62%)
    10 / 99 (10.10%)
    2 / 35 (5.71%)
         occurrences all number
    0
    9
    11
    2
    Urinary tract infection
         subjects affected / exposed
    0 / 99 (0.00%)
    0 / 37 (0.00%)
    2 / 99 (2.02%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    2
    2
    Viral infection
         subjects affected / exposed
    2 / 99 (2.02%)
    4 / 37 (10.81%)
    9 / 99 (9.09%)
    3 / 35 (8.57%)
         occurrences all number
    3
    4
    12
    5

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Apr 2009
    No subjects had been enrolled in the study at the time of this amendment. This amendment: - Identified a new Sponsor Clinical Program Director and Clinical Research Physician - Corrected an inconsistency in definition of positive and negative purified Protein derivative (PPD) tests - Reduced the number of blood draws by consolidating laboratory tests and decreasing the number of PCDAI assessments - Required North American site to use the PPD test; Rest of World sites had the option of using the QuantiFERON®-TB GOLD (QFT-GOLD) if the PPD test was not available. - Generalized location of study sites - Removed C-reactive protein (CRP) from the standard clinical chemistry laboratory battery - Corrected an inconsistency in timing of chest x-ray - Changed the method and timing of the wrist x-ray used to calculate bone age - Removed the “up to the age of 14 years” restriction on the Work Productivity and Activity Impairment Questionnaire for CD (WPAI:CD) - Specified the WPAI:CD assessments obtained during reinduction - Clarified administration of WPAI:CD for children and WPAI:CD for working individuals - Revised the wording of some WPAI:CD questions and made minor format changes - Corrected definition of scores for height velocity on PCDAI - Clarified rationale for calculating the PCDAI - Changed “rescue medication” to “rescue therapy” throughout
    20 Oct 2009
    At the time of this amendment, 4 subjects had been enrolled in the study. This amendment: - Updated fax number for UCB study physician - Specified the assessments used to determine the effect of treatment on the subject’s CD (exploratory variable) - Added a provision to do the PK assessments on the 10 subjects who completed the Induction Period in 2 stages depending on rate of completion of the Induction Period in each age group - Modified inclusion criteria for duration of CD diagnosis (Inclusion #2), use of parenteral corticosteroids prior to Screening (Inclusion #8 and Exclusion #12), use of antibiotics (Inclusion #8), and exclusion criteria for prior use of anti-TNFα agents (Exclusion #9) to better correspond with clinical practice Clarified Exclusion criteria #1 (regarding draining fistula) and #16 (regarding negative test results for immunoglobulin G (IgG) against Varicella zoster) Clarified hormonal contraceptives, added duration of contraceptive use in after discontinuation of study treatment to reflect updates to company core data sheet, and reconciled an inconsistency in wording between text in the protocol summary section and Section 9.2 (Exclusion #26)
    20 Oct 2009
    - Added Exclusion criterion #28 dealing with hypersensitivity or intolerance to CZP or polyethylene glycol (PEG) - Added visit windows to accommodate occasional scheduling difficulties with the understanding that study treatment cannot exceed a total of 60 weeks - Deleted the Week 13 visit (PK and immunologic blood sampling) to reduce the number of study visits - Updated number of clinical studies conducted and changed reference to “current” Investigator Brochure rather than specifying the version - Specified the corticosteroid dose that would be considered rescue therapy - Added a wrist x-ray at Week 60 in addition to Week 0 to assess growth over the course of treatment - Incorporated previous administrative amendment regarding timing of vital signs in relationship to dosing - Expanded use of QFT-Gold to North American sites (all sites can use either PPD or QFT-Gold) to facilitate TB testing at the sites - Corrected an error in location of TB questionnaire - Corrected an inconsistency in laboratory values used to calculate the Week 0 PCDAI score - Updated the entire AE section to reflect current standard operating procedures and template language - Added statistical analyses of Tanner stage

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    14 Jun 2011
    Enrollment was temporarily suspended on 14-Jun-2011, in agreement with the study’s DSMB recommendation, due to a higher than expected number of premature withdrawals. Enrollment was permanently terminated in Apr2012 following discussion with the Food and Drug Administration (FDA).
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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