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    Clinical Trial Results:
    Exploration of TNF-alpha Blockade with golimumab in the Induction of Clinical Remission in Patients with Early peripheral SpondyloArthritis (SpA) according to ASAS-criteria (‘CRESPA’).

    Summary
    EudraCT number
    2011-003678-97
    Trial protocol
    BE  
    Global end of trial date
    30 Apr 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    19 Sep 2021
    First version publication date
    19 Sep 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    AGO/2011/005
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Ghent University Hospital
    Sponsor organisation address
    Corneel Heymanslaan 10, Ghent, Belgium, 9000
    Public contact
    Hiruz CTU, Ghent University Hospital, 32 93320500, hiruz.ctu@uzgent.be
    Scientific contact
    Hiruz CTU, Ghent University Hospital, 32 93320500, hiruz.ctu@uzgent.be
    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
    07 May 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Mar 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Apr 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To explore the potential of an induction therapy with the TNF-blocking agent golimumab (Simponi® in a very early disease stage (less than 3 months of symptom duration) of patients with predominant peripheral Spondyloarthritis (SpA), classified according to the new ASAS-criteria. In the open-label ‘CRESPA-extension’ part of the study, we want to investigate the long-term safety and efficacy of golimumab administered every 4 weeks at a dose of 50 mg subcutaneously (SC) for a total period of 116 weeks (104 weeks golimumab monotherapy + 12 weeks combination therapy with methotrexate 10-15 mg weekly).
    Protection of trial subjects
    Ethics review and approval, informed consent, supportive care and routine monitoring.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Oct 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    29 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 60
    Worldwide total number of subjects
    60
    EEA total number of subjects
    60
    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)
    60
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    84 patients were screened in the period from 01-10-2011 till 18-03-2019. 60 patients were included, 60 patients were randomised. 59 patients were included and completed the trial. End of trial notification was dated 18-03-2019 (last patient last visit) and submitted to EC and CA 23-05-2019.

    Pre-assignment
    Screening details
    Inclusion Criteria: - ≥ 18 years of age - meet the new Assessment of SpondyloArthritis (ASAS) criteria for peripheral spondyloarthritis: -1 of the Peripheral Spondyloarthritis (SpA) features - Onset of peripheral SpA symptoms ≤ 3 months prior to the screening visit - active disease at screening and baseline

    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator
    Blinding implementation details
    The randomisation and blinding was completely performed by Theorem Clinical Research. The decision to unblind a patient will be made by the study physician and was extensively documented in the patient file. Theorem Clinical Research provided sealed envelopes which were kept in the clinical study master file at the department of Rheumatology, University Hospital Gent.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Baseline CRESPA study: Placebo
    Arm description
    -
    Arm type
    Active comparator

    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
    The prefilled syringe with golimumab or placebo will be administrated subcutaneously every 4 weeks.

    Arm title
    Baseline CRESPA study: Golimumab 50mg (Simponi®)
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Simponi
    Investigational medicinal product code
    CAS 476181-74-5
    Other name
    golimumab
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The prefilled syringe with golimumab or placebo will be administrated subcutaneously every 4 weeks.

    Number of subjects in period 1
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®)
    Started
    20
    40
    Completed
    20
    40
    Period 2
    Period 2 title
    CERPA Study
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    CRESPA study: Placebo
    Arm description
    -
    Arm type
    Active comparator

    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
    The prefilled syringe with golimumab or placebo will be administrated subcutaneously every 4 weeks.

    Arm title
    CRESPA study: Golimumab 50mg (Simponi®)
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Simponi
    Investigational medicinal product code
    CAS 476181-74-5
    Other name
    golimumab
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The prefilled syringe with golimumab or placebo will be administrated subcutaneously every 4 weeks.

    Number of subjects in period 2
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Started
    20
    40
    Completed
    20
    39
    Not completed
    0
    1
         safety issues
    -
    1
    Period 3
    Period 3 title
    CERPA extension
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    Treatment arm
    Arm description
    The ‘CRESPA-Extension’ part of the study is designed to investigate safety and long-term efficacy of golimumab in peripheral SpA patients with a major response to golimumab or a disease flare upon withdrawal of golimumab after reaching initial remission in the ‘CRESPA’ study. In the last 3 months of the CRESPA-Extension study part, golimumab treatment will be combined with methotrexate in order to explore the possibility that co-medication with methotrexate would allow for the discontinuation of golimumab treatment at week 116, thus providing clues of the potential of “biological-free” remission. 29 were not included in the extension study because of remission.
    Arm type
    Experimental

    Investigational medicinal product name
    Ledertrexate
    Investigational medicinal product code
    Other name
    Methotrexate
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Methotrexate will be administered orally with a total weekly dosage of 10 to 15 mg, meaning 4 to 6 tablets of 2.5mg weekly (104 weeks golimumab monotherapy + 12 weeks combination therapy with methotrexate 10-15 mg weekly).

    Investigational medicinal product name
    Simponi
    Investigational medicinal product code
    CAS 476181-74-5
    Other name
    golimumab
    Pharmaceutical forms
    Solution for injection in pre-filled syringe
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    The prefilled syringe with golimumab or placebo will be administrated subcutaneously every 4 weeks (104 weeks golimumab monotherapy + 12 weeks combination therapy with methotrexate 10-15 mg weekly).

    Number of subjects in period 3 [1]
    Treatment arm
    Started
    31
    Completed
    28
    Not completed
    3
         pregnancy on 13-03-2016
    1
         Lost to follow-up
    1
         safety issues
    1
    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: 29 were not included in the extension study because of remission.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Baseline CRESPA study: Placebo
    Reporting group description
    -

    Reporting group title
    Baseline CRESPA study: Golimumab 50mg (Simponi®)
    Reporting group description
    -

    Reporting group values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) Total
    Number of subjects
    20 40 60
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    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)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    42.3 ± 13.7 38.3 ± 13.2 -
    Gender categorical
    Units: Subjects
        Female
    13 26 39
        Male
    7 14 21
    HLA B27 positive
    Units: Subjects
        yes
    13 20 33
        no
    7 20 27
    Concomitant NSAIDs use at baseline,
    Units: Subjects
        yes
    18 32 50
        no
    2 8 10
    Anterior uveitis, past or present
    Units: Subjects
        yes
    0 1 1
        no
    20 39 59
    IBD, past or present
    Units: Subjects
        yes
    1 0 1
        no
    19 40 59
    Preceding infection
    Units: Subjects
        yes
    2 6 8
        no
    18 34 52
    Skin and/or nail psoriasis
    Units: Subjects
        yes
    8 17 25
        no
    12 23 35
    patients with elevated CRP (≥5 mg/L)
    Units: Subjects
        yes
    15 24 39
        no
    5 16 21
    Sacroiliitis on MRI
    Units: Subjects
        yes
    9 12 21
        no
    11 28 39
    Family history of SpA
    Units: Subjects
        yes
    8 13 21
        no
    12 27 39
    Inflammatory back pain (history/presence)
    Units: Subjects
        yes
    2 5 7
        no
    18 35 53
    Symptom duration
    Units: weeks
        arithmetic mean (standard deviation)
    4.4 ± 2 5.2 ± 2.8 -
    NSAID index
    Units: index
        median (inter-quartile range (Q1-Q3))
    100 (65.1 to 100) 89.3 (35 to 100) -

    End points

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    End points reporting groups
    Reporting group title
    Baseline CRESPA study: Placebo
    Reporting group description
    -

    Reporting group title
    Baseline CRESPA study: Golimumab 50mg (Simponi®)
    Reporting group description
    -
    Reporting group title
    CRESPA study: Placebo
    Reporting group description
    -

    Reporting group title
    CRESPA study: Golimumab 50mg (Simponi®)
    Reporting group description
    -
    Reporting group title
    Treatment arm
    Reporting group description
    The ‘CRESPA-Extension’ part of the study is designed to investigate safety and long-term efficacy of golimumab in peripheral SpA patients with a major response to golimumab or a disease flare upon withdrawal of golimumab after reaching initial remission in the ‘CRESPA’ study. In the last 3 months of the CRESPA-Extension study part, golimumab treatment will be combined with methotrexate in order to explore the possibility that co-medication with methotrexate would allow for the discontinuation of golimumab treatment at week 116, thus providing clues of the potential of “biological-free” remission. 29 were not included in the extension study because of remission.

    Primary: Clinical Remission Status at week 24

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    End point title
    Clinical Remission Status at week 24
    End point description
    The primary endpoint of the study is the induction of clinical remission (complete resolution of synovitis/dactylitis/enthesitis which was present at baseline) and prevention of newly developing peripheral and/or axial spondylarthritis signs). The primary analysis will be a comparison at 24 weeks of the percentage of patients in clinical remission in the group treated with the Tumor Necrosis Factor (TNF)-blocking agent versus placebo.
    End point type
    Primary
    End point timeframe
    At week 24
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: number (n)
    4
    30
    Statistical analysis title
    Clinical Remission Status
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Fisher exact
    Confidence interval

    Secondary: Patient global assessment of disease activity at week 24

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    End point title
    Patient global assessment of disease activity at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: 0–10 NRS scale
        median (inter-quartile range (Q1-Q3))
    8 (4 to 9)
    7 (5 to 8)
    6 (4 to 8)
    1 (0 to 3)
    Statistical analysis title
    PGA of disease activity
    Comparison groups
    Baseline CRESPA study: Golimumab 50mg (Simponi®) v Baseline CRESPA study: Placebo v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Patient global assessment of pain at week 24

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    End point title
    Patient global assessment of pain at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: 0–10 NRS scale
        median (inter-quartile range (Q1-Q3))
    6 (4 to 8)
    5 (4 to 7)
    6 (3 to 7)
    2 (0 to 4)
    Statistical analysis title
    PGA of pain
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: The improvement in the tender joint count at week 24

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    End point title
    The improvement in the tender joint count at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: tender joint count
        median (inter-quartile range (Q1-Q3))
    4 (2 to 9)
    5 (3 to 8)
    5 (1 to 7)
    0 (0 to 2)
    Statistical analysis title
    tender joint count
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: The improvement in the swollen joint count at week 24

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    End point title
    The improvement in the swollen joint count at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: swollen joint count
        median (inter-quartile range (Q1-Q3))
    3 (2 to 5)
    4 (2 to 5)
    1 (0 to 6)
    0 (0 to 1)
    Statistical analysis title
    swollen joint count
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®) v Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: The improvement in dactylitis at week 24

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    End point title
    The improvement in dactylitis at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: patients with dactylitis
    9
    15
    12
    7
    Statistical analysis title
    patients with dactylitis
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.003
    Method
    Fisher exact
    Confidence interval

    Secondary: The improvement in enthesitis at week 24

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    End point title
    The improvement in enthesitis at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    39
    20
    40
    Units: patients with enthesitis
    9
    16
    16
    7
    Statistical analysis title
    Patients with enthesitis
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    119
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Fisher exact
    Confidence interval

    Secondary: Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 40 at week 24

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    End point title
    Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 40 at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: number (n)
    3
    20
    Statistical analysis title
    pSpARC 40%
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011
    Method
    Fisher exact
    Confidence interval

    Secondary: Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 50 at week 24

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    End point title
    Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 50 at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: number (n)
    3
    22
    Statistical analysis title
    pSpARC 50%
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.005
    Method
    Fisher exact
    Confidence interval

    Secondary: Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 70 at week 24

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    End point title
    Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 70 at week 24
    End point description
    End point type
    Secondary
    End point timeframe
    At week 24
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: number (n)
    3
    16
    Statistical analysis title
    pSpARC 70%
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.077
    Method
    Fisher exact
    Confidence interval

    Secondary: Patient global assessment of disease activity at week 12

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    End point title
    Patient global assessment of disease activity at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40 [1]
    Units: 0–10 NRS scale
        median (inter-quartile range (Q1-Q3))
    8 (4 to 9)
    7 (5 to 8)
    6 (4 to 7)
    2 (1 to 5)
    Notes
    [1] - 40
    Statistical analysis title
    PGA of disease activity
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.002
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Patient global assessment of pain at week 12

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    End point title
    Patient global assessment of pain at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: 0–10 NRS scale
        median (inter-quartile range (Q1-Q3))
    6 (4 to 8)
    5 (4 to 7)
    6 (3 to 7)
    1 (1 to 4)
    Statistical analysis title
    PGA of pain
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: The improvement in the tender joint count at week 12

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    End point title
    The improvement in the tender joint count at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: tender joint count
        median (inter-quartile range (Q1-Q3))
    4 (2 to 9)
    5 (3 to 8)
    4 (1 to 11)
    0 (0 to 2)
    Statistical analysis title
    tender joint count
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: The improvement in the swollen joint count at week 12

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    End point title
    The improvement in the swollen joint count at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: swollen joint count
        median (inter-quartile range (Q1-Q3))
    3 (2 to 5)
    4 (2 to 5)
    2 (0 to 7)
    0 (0 to 0)
    Statistical analysis title
    swollen joint count
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: The improvement in dactylitis at week 12

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    End point title
    The improvement in dactylitis at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: patients with dactylitis
    9
    15
    8
    3
    Statistical analysis title
    Patients with dactylitis
    Comparison groups
    Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v Baseline CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.004
    Method
    Fisher exact
    Confidence interval

    Secondary: The improvement in enthesitis at week 12

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    End point title
    The improvement in enthesitis at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    Baseline CRESPA study: Placebo Baseline CRESPA study: Golimumab 50mg (Simponi®) CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    20
    40
    Units: patients with enthesisits
    9
    16
    5
    6
    Statistical analysis title
    Patients with enthesitis
    Comparison groups
    Baseline CRESPA study: Placebo v Baseline CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    120
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.48
    Method
    Fisher exact
    Confidence interval

    Secondary: Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 40 at week 12

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    End point title
    Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 40 at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: number (n)
    4
    23
    Statistical analysis title
    pSpARC 40%
    Comparison groups
    CRESPA study: Golimumab 50mg (Simponi®) v CRESPA study: Placebo
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.007
    Method
    Fisher exact
    Confidence interval

    Secondary: Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 50 at week 12

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    End point title
    Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 50 at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: number (n)
    4
    22
    Statistical analysis title
    pSpARC 50%
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.013
    Method
    Fisher exact
    Confidence interval

    Secondary: Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 70 at week 12

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    End point title
    Patients achieving Peripheral Spondyloarthritis Response Criteria pSpARC 70 at week 12
    End point description
    End point type
    Secondary
    End point timeframe
    At week 12
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: pSpARC 70%
    3
    20
    Statistical analysis title
    pSpARC 70%
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.011
    Method
    Fisher exact
    Confidence interval

    Secondary: Bath AS Disease Activity Index (BASDAI) 50% response

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    End point title
    Bath AS Disease Activity Index (BASDAI) 50% response
    End point description
    End point type
    Secondary
    End point timeframe
    At 24 weeks
    End point values
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects analysed
    20
    40
    Units: percentage of patients
    3
    29
    Statistical analysis title
    BASDAI 50% response
    Comparison groups
    CRESPA study: Placebo v CRESPA study: Golimumab 50mg (Simponi®)
    Number of subjects included in analysis
    60
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.05
    Method
    Fisher exact
    Confidence interval

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Overall study
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    CRESPA study: Placebo
    Reporting group description
    -

    Reporting group title
    CRESPA study: Golimumab 50mg (Simponi®)
    Reporting group description
    -

    Serious adverse events
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    4 / 40 (10.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Papillar carcinoma of the thyroidgland
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Flare of peripheral spondyloarthritis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Worsening of artritis
         subjects affected / exposed
    0 / 20 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicula fracture
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Acute cholecystitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nefrolithiasis en nefritis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Infectious bronchitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    CRESPA study: Placebo CRESPA study: Golimumab 50mg (Simponi®)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 20 (55.00%)
    26 / 40 (65.00%)
    Infections and infestations
    Infectious AE
         subjects affected / exposed
    11 / 20 (55.00%)
    26 / 40 (65.00%)
         occurrences all number
    25
    52

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Jun 2012
    Amendment 2: reasons for the substantial amendment: French ICF and questionnaire
    17 Apr 2013
    Amendment 3: Reasons for the substantial amendment: Rescue medication sulfasalazine/corticosteroid injections will be replaced by Golimumab 50 mg sc. Description: Starting at week 12 and until week 20, there will be an option to start rescue medication (in total 6 injections) with Golimumab 50mg sc every 4 weeks if all criteria for starting rescue medication are met. Reasons for the substantial amendment: Rescue medication sulfasalazine/corticosteroid injections will be replaced by Golimumab 50 mg sc. Description: In case of clinical relapse (after having reached "sustained clinical remission" at 2 consecutive visits), patients will have the option to receive open-label treatment with golimumab at a dose of 50 mg SC every 4 weeks. For this "relapse treatment phase" the open-label study medication (6 injections planned for visits week 24-44) will be used. Reasons for the substantial amendment: Visits at week 60 and 72 are extra. Investigators wish to clinically evaluate the patients a while longer.
    05 Aug 2013
    Amendment 4: Reasons for the substantial amendment: A 2-year open-label extension study to explore the long-term safety and efficacy of golimumab 50 mg SC every 4 weeks in patients that experienced major improvement of a clinical flare after achieving initial clinical remission. Description: Exploration of TNF-alpha blockade with golimumab in the induction of clinical remission in patients with early peripheral spondyloarthitis (SpA) according to ASAS-criteria. (‘CRESPA’), including a 2-year open-label extension study to explore the long-term safety and efficacy of golimumab 50 mg SC every 4 weeks in patients that experienced major improvement of a clinical flare after achieving initial clinical remission (‘CRESPA-extension’). In the open-label ‘CRESPA-extension’ part of the study, we want to investigate the long-term safety and efficacy of golimumab administered every 4 weeks at a dose of 50 mg subcutaneously (SC). Subjects will be allowed to participate in the ‘CRESPA-Extension’ part of the study if they are considered good candidates for chronic anti-TNF treatment and fulfill one of the following 2 scenarios:
    26 Feb 2015
    Amendment 5: reasons for the substantial amendment: Changes in conduct or management of the trial -Patients that are already more than one year in drug-free remission are considered to be in stable sustained remission and will not be entered in the CRESPA extension part of the study anymore. However, for patients that are already in drug-free remission for more than one year at the time of approval of version 6.0 of the protocol, a transitional measure will be applicable which allows them to still enter the CRESPA extension for a period of up to 2 years after reaching initial clinical remission. -Adding of an ultrasound evaluation at the last visit of the CRESPA extension part. -Additional info on labeling for the extension study; The open-label Golimumab syringes will be delivered by Theorem to the Ghent University Hospital Department of Rheumatology (via the Ghent University Hospital Pharmacy) in bulk with a global label. Individual syringes will be labeled study-specific following the hospital law by the Ghent University Hospital Pharmacy before dispensing to the patients.
    08 Feb 2016
    Amendment 6 Reasons for the substantial amendment: - Changes in safety or integrity of trial subjects - Changes in interpretation of scientific documents/value of the trial - Changes in conduct or management of the trial Description: - A 12 weeks combination therapy with methotrexate 10-15 mg weekly was added in the open-label CRESPA extension part. - Clarification of the primary analysis: The primary analysis will be a comparison at 24 weeks of the percentage of patients in clinical remissionin the group treated with the TNF-blocking agent versus placebo (for patients who were treated via the open-label Golimumab escape arm, an approach based upon last observation carried forward (LOCF) and non-responder imputation (NRI) will be used). - There will be a comparison at 12 (and if applicable at 24) weeks of the percentage of patients with a PSpARC 40 response in the group treated with the TNF-blocking agent versus placebo. - Changes were made to the secondary endpoints - Three months of follow-up after CRESPA-extension: After receiving 104 weeks of open label monotherapy with golimumab 50 mg SC every 4 weeks in the CRESPA–extension study part, the patients will be offered an additional 12 weeks of open label golimumab 50 mg SC every 4 weeks, but now in combination with methotrexate. After these 12 weeks methotrexate therapy will be continued (if well tolerated), but golimumab will be stopped and the patients will further receive appropriate follow-up according to current best clinical practice guidelines for the treatment of (axial and/or peripheral) spondyloarthritis. As before, clinical evaluations, patient reported outcomes and laboratory evaluations will be recorded in the local registry for spondyloarthritis (Be-GIANT).

    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

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/28213565
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