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    Clinical Trial Results:
    A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF-OF-CONCEPT STUDY TO EVALUATE THE EFFICACY AND SAFETY OF UCB5857 OVER 12 WEEKS IN SUBJECTS WITH PRIMARY SJӦGREN’S SYNDROME

    Summary
    EudraCT number
    2014-004523-51
    Trial protocol
    GB   ES   FR   SE   GR   IT  
    Global end of trial date
    27 Sep 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    13 Oct 2018
    First version publication date
    13 Oct 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    SS0004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02610543
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    UK Registered Branch of UCB Pharma SA
    Sponsor organisation address
    208 Bath Road, Slough, United Kingdom, SL1 3WE
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, 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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    03 May 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Sep 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate the efficacy on overall disease activity and safety of UCB5857 added to current treatment relative to placebo in subjects with primary Sjögren’s Syndrome (pSS).
    Protection of trial subjects
    During the conduct of the study all subjects were closely monitored.
    Background therapy
    Background therapy as permitted in the protocol.
    Evidence for comparator
    Not applicable.
    Actual start date of recruitment
    28 Oct 2015
    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
    France: 6
    Country: Number of subjects enrolled
    Italy: 4
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United Kingdom: 9
    Worldwide total number of subjects
    27
    EEA total number of subjects
    27
    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)
    18
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study started to enroll patients in October 2015 and concluded prematurely in September 2017.

    Pre-assignment
    Screening details
    The Participant Flow refers to the Full Analysis Set (FAS).

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Placebo
    Arm description
    Participants received a daily dose of matching placebo for 12 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    PBO
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects were administered capsules of matching placebo once daily, for a duration of 12 weeks.

    Arm title
    UCB5857
    Arm description
    Participants received a daily dose of 45 mg UCB5857 for 12 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    UCB5857
    Investigational medicinal product code
    UCB5857
    Other name
    Seletalisib
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects were administered capsules of the investigational medicinal product (IMP) at doses of 5, 10, and 30 milligrams (mg) adding up to a total dose of 45 mg, once daily, for a duration of 12 weeks.

    Number of subjects in period 1
    Placebo UCB5857
    Started
    14
    13
    Completed
    12
    8
    Not completed
    2
    5
         Protocol deviation
    1
    -
         Adverse event, non-fatal
    1
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received a daily dose of matching placebo for 12 weeks.

    Reporting group title
    UCB5857
    Reporting group description
    Participants received a daily dose of 45 mg UCB5857 for 12 weeks.

    Reporting group values
    Placebo UCB5857 Total
    Number of subjects
    14 13 27
    Age categorical
    Units: Subjects
        <=18 years
    0 0 0
        Between 18 and 65 years
    9 9 18
        >=65 years
    5 4 9
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    60.2 ± 9.9 52.2 ± 16.1 -
    Gender categorical
    Units: Subjects
        Female
    13 12 25
        Male
    1 1 2

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    Participants received a daily dose of matching placebo for 12 weeks.

    Reporting group title
    UCB5857
    Reporting group description
    Participants received a daily dose of 45 mg UCB5857 for 12 weeks.

    Subject analysis set title
    Placebo (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received a daily dose of matching placebo for 12 weeks.

    Subject analysis set title
    UCB5857 (SS)
    Subject analysis set type
    Safety analysis
    Subject analysis set description
    Participants received a daily dose of 45 mg UCB5857 for 12 weeks.

    Subject analysis set title
    Placebo (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received a daily dose of matching placebo for 12 weeks.

    Subject analysis set title
    UCB5857 (FAS)
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Participants received a daily dose of 45 mg UCB5857 for 12 weeks.

    Primary: Change from Baseline to Week 12 in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI)

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    End point title
    Change from Baseline to Week 12 in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI)
    End point description
    The ESSDAI is a physician administered questionnaire containing 12 organ-specific domains designed to measure disease activity.
    End point type
    Primary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    14
    13
    Units: scores on a scale
    least squares mean (standard error)
        scores on a scale
    -2.8 ± 1.5
    -5.4 ± 1.7
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on ESSDAI using mixed model for repeated measures (MMRM) analysis with covariates of treatment, visit, Baseline ESSDAI, and treatment by visit interaction. Note: A negative change from baseline indicates improvement while a positive change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.266
    Method
    MMRM
    Parameter type
    Difference in ESSDAI score
    Point estimate
    -2.59
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -7.3
         upper limit
    2.11

    Secondary: Change from Baseline to Week 4 in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI)

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    End point title
    Change from Baseline to Week 4 in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI)
    End point description
    The ESSDAI is a physician administered questionnaire containing 12 organ-specific domains designed to measure disease activity.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    14
    13
    Units: scores on a scale
    least squares mean (standard error)
        scores on a scale
    -1.5 ± 1.2
    -5.0 ± 1.2
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on ESSDAI using mixed model for repeated measures (MMRM) analysis with covariates of treatment, visit, Baseline ESSDAI, and treatment by visit interaction. Note: A negative change from baseline indicates improvement while a positive change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in ESSDAI score
    Point estimate
    -3.49
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.97
         upper limit
    -0.02

    Secondary: Change from Baseline to Week 8 in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI)

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    End point title
    Change from Baseline to Week 8 in the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI)
    End point description
    The ESSDAI is a physician administered questionnaire containing 12 organ-specific domains designed to measure disease activity.
    End point type
    Secondary
    End point timeframe
    Week 8
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    13
    10
    Units: scores on a scale
    least squares mean (standard error)
        scores on a scale
    -0.6 ± 1.7
    -4.7 ± 1.9
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on ESSDAI using mixed model for repeated measures (MMRM) analysis with covariates of treatment, visit, Baseline ESSDAI, and treatment by visit interaction. Note: A negative change from baseline indicates improvement while a positive change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    23
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in ESSDAI score
    Point estimate
    -4.04
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -9.3
         upper limit
    1.22

    Secondary: Change from Baseline to Week 12 in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)

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    End point title
    Change from Baseline to Week 12 in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)
    End point description
    The ESSPRI is a patient completed questionnaire to assess subjective patient symptoms, which includes 3 domains (dryness, limb pain and fatigue).
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    12
    8
    Units: scores on a scale
    least squares mean (standard error)
        scores on a scale
    -0.573 ± 0.555
    -2.125 ± 0.675
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on ESSPRI using MMRM analysis with covariates of treatment, visit, Baseline ESSPRI, and treatment by visit interaction. Note: A negative change from baseline indicates improvement while a positive change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in ESSPRI score
    Point estimate
    -1.55
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -3.39
         upper limit
    0.28

    Secondary: Change from Baseline to Week 4 in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)

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    End point title
    Change from Baseline to Week 4 in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)
    End point description
    The ESSPRI is a patient completed questionnaire to assess subjective patient symptoms, which includes 3 domains (dryness, limb pain and fatigue).
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    14
    12
    Units: scores on a scale
    least squares mean (standard error)
        scores on a scale
    -1.376 ± 0.411
    -1.617 ± 0.460
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on ESSPRI using MMRM analysis with covariates of treatment, visit, Baseline ESSPRI, and treatment by visit interaction. Note: A negative change from baseline indicates improvement while a positive change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    26
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in ESSPRI score
    Point estimate
    -0.24
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.53
         upper limit
    1.05

    Secondary: Change from Baseline to Week 8 in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)

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    End point title
    Change from Baseline to Week 8 in the EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)
    End point description
    The ESSPRI is a patient completed questionnaire to assess subjective patient symptoms, which includes 3 domains (dryness, limb pain and fatigue).
    End point type
    Secondary
    End point timeframe
    Week 8
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    13
    9
    Units: scores on a scale
    least squares mean (standard error)
        scores on a scale
    -0.741 ± 0.439
    -1.922 ± 0.505
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on ESSPRI using MMRM analysis with covariates of treatment, visit, Baseline ESSPRI, and treatment by visit interaction. Note: A negative change from baseline indicates improvement while a positive change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in ESSPRI score
    Point estimate
    -1.18
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.58
         upper limit
    0.22

    Secondary: Change from Baseline to Week 12 in the stimulated salivary flow

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    End point title
    Change from Baseline to Week 12 in the stimulated salivary flow
    End point description
    The stimulated salivary flow test evaluates the status of salivary glands and the production of saliva. Saliva is collected into a graduated container after gustatory provocation with a stimulant.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    12
    6
    Units: mL/min
    least squares mean (standard error)
        mL/min
    -0.105 ± 0.081
    -0.084 ± 0.113
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on Stimulated Salivary Flow Rate using MMRM analysis with covariates of treatment, visit, Baseline Stimulated Salivary Flow Rate, and treatment by visit interaction. Note: A positive change from baseline indicates improvement while a negative change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in Stimulated Salivary Flow
    Point estimate
    0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.27
         upper limit
    0.31

    Secondary: Change from Baseline to Week 4 in the stimulated salivary flow

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    End point title
    Change from Baseline to Week 4 in the stimulated salivary flow
    End point description
    The stimulated salivary flow test evaluates the status of salivary glands and the production of saliva. Saliva is collected into a graduated container after gustatory provocation with a stimulant.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    13
    10
    Units: mL/min
    least squares mean (standard error)
        mL/min
    -0.189 ± 0.081
    0.063 ± 0.093
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on Stimulated Salivary Flow Rate using MMRM analysis with covariates of treatment, visit, Baseline Stimulated Salivary Flow Rate, and treatment by visit interaction. Note: A positive change from baseline indicates improvement while a negative change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    23
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in Stimulated Salivary Flow
    Point estimate
    0.25
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0
         upper limit
    0.51

    Secondary: Change from Baseline to Week 8 in the stimulated salivary flow

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    End point title
    Change from Baseline to Week 8 in the stimulated salivary flow
    End point description
    The stimulated salivary flow test evaluates the status of salivary glands and the production of saliva. Saliva is collected into a graduated container after gustatory provocation with a stimulant.
    End point type
    Secondary
    End point timeframe
    Week 8
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    13
    7
    Units: mL/min
    least squares mean (standard error)
        mL/min
    -0.116 ± 0.096
    0.254 ± 0.126
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on Stimulated Salivary Flow Rate using MMRM analysis with covariates of treatment, visit, Baseline Stimulated Salivary Flow Rate, and treatment by visit interaction. Note: A positive change from baseline indicates improvement while a negative change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in Stimulated Salivary Flow
    Point estimate
    0.37
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.04
         upper limit
    0.7

    Secondary: Change from Baseline to Week 12 in the unstimulated salivary flow

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    End point title
    Change from Baseline to Week 12 in the unstimulated salivary flow
    End point description
    The unstimulated salivary flow test evaluates the status of salivary glands and the production of saliva. Saliva is collected into a graduated container without gustatory provocation.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    12
    6
    Units: mL/min
    least squares mean (standard error)
        mL/min
    -0.024 ± 0.021
    -0.042 ± 0.029
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on Unstimulated Salivary Flow Rate using MMRM analysis with covariates of treatment, visit, Baseline Unstimulated Salivary Flow Rate, and treatment by visit interaction. Note: A positive change from baseline indicates improvement while a negative change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in Unstimulated Salivary Flow
    Point estimate
    -0.02
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.1
         upper limit
    0.06

    Secondary: Change from Baseline to Week 4 in the unstimulated salivary flow

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    End point title
    Change from Baseline to Week 4 in the unstimulated salivary flow
    End point description
    The unstimulated salivary flow test evaluates the status of salivary glands and the production of saliva. Saliva is collected into a graduated container without gustatory provocation.
    End point type
    Secondary
    End point timeframe
    Week 4
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    14
    10
    Units: mL/min
    least squares mean (standard error)
        mL/min
    0.060 ± 0.049
    0.012 ± 0.059
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on Unstimulated Salivary Flow Rate using MMRM analysis with covariates of treatment, visit, Baseline Unstimulated Salivary Flow Rate, and treatment by visit interaction. Note: A positive change from baseline indicates improvement while a negative change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in Unstimulated Salivary Flow
    Point estimate
    -0.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.21
         upper limit
    0.12

    Secondary: Change from Baseline to Week 8 in the unstimulated salivary flow

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    End point title
    Change from Baseline to Week 8 in the unstimulated salivary flow
    End point description
    The unstimulated salivary flow test evaluates the status of salivary glands and the production of saliva. Saliva is collected into a graduated container without gustatory provocation.
    End point type
    Secondary
    End point timeframe
    Week 8
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    13
    7
    Units: mL/min
    least squares mean (standard error)
        mL/min
    0.013 ± 0.034
    0.011 ± 0.044
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on Unstimulated Salivary Flow Rate using MMRM analysis with covariates of treatment, visit, Baseline Unstimulated Salivary Flow Rate, and treatment by visit interaction. Note: A positive change from baseline indicates improvement while a negative change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    20
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    MMRM
    Parameter type
    Difference in Unstimuated Salivary Flow
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.12
         upper limit
    0.12

    Secondary: Change in sum total tear secretion from Baseline to Week 12 measured by Schirmer´s I test (without anesthesia)

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    End point title
    Change in sum total tear secretion from Baseline to Week 12 measured by Schirmer´s I test (without anesthesia)
    End point description
    The Schirmer's test measures basic tear function. A 35 mm x 5 mm size paper strip is inserted into each eye for a period of 5 minutes to measure the production of tears.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    Placebo (FAS) UCB5857 (FAS)
    Number of subjects analysed
    13
    8
    Units: mm
    least squares mean (standard error)
        mm
    0.5 ± 2.6
    -0.9 ± 3.3
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The difference presented is 'UCB5857 45 mg minus Placebo'. Analysis performed on Schirmer’s I Test Sum Score using ANCOVA with covariates of treatment and Baseline Schirmer’s I Test Sum Score. Note: A positive change from baseline indicates improvement while a negative change from baseline indicates worsening.
    Comparison groups
    Placebo (FAS) v UCB5857 (FAS)
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    ANCOVA
    Parameter type
    Difference in Schirmer´s I score
    Point estimate
    -1.41
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -10.35
         upper limit
    7.52

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline (Week 1) to Day 114 or 30 days after final dose, in case of early termination
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Placebo (SS)
    Reporting group description
    Participants received a daily dose of matching placebo for 12 weeks.

    Reporting group title
    UCB5857 (SS)
    Reporting group description
    Participants received a daily dose of 45 mg UCB5857 for 12 weeks.

    Serious adverse events
    Placebo (SS) UCB5857 (SS)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 14 (7.14%)
    3 / 13 (23.08%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myopathy
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Placebo (SS) UCB5857 (SS)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 14 (92.86%)
    12 / 13 (92.31%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Hypertension
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Hypersensitivity
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Drug hypersensitivity
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    Chest pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Menorrhagia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Dysmenorrhoea
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Post procedural contusion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Post procedural swelling
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Procedural pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Neutrophil count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    White blood cell count decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 14 (14.29%)
    3 / 13 (23.08%)
         occurrences all number
    3
    3
    Dizziness
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Dysgeusia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Sensory disturbance
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Eye disorders
    Dry eye
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Tinnitus
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Tympanic membrane disorder
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    3
    Diarrhoea
         subjects affected / exposed
    0 / 14 (0.00%)
    5 / 13 (38.46%)
         occurrences all number
    0
    8
    Nausea
         subjects affected / exposed
    1 / 14 (7.14%)
    2 / 13 (15.38%)
         occurrences all number
    1
    5
    Abdominal distension
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Colitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Vomiting
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Oral pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Tooth loss
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Renal impairment
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    4
    Dermatitis allergic
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Erythema multiforme
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Dermatitis contact
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Psoriasis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Eczema
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Purpura
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Lichen planus
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Skin exfoliation
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Rash vesicular
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Skin hypertrophy
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Neck pain
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Arthralgia
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Costochondritis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Pain in extremity
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Sjögren's syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Fracture nonunion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Muscle contracture
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Cell death
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Decreased appetite
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Skin infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Tracheitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Gingivitis
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Aug 2015
    The rationale for this substantial amendment dated 17-Aug-2015 was to consolidate feedback from Competent Authorities in United Kingdom (UK), France, and Spain, resulting in a new core protocol. The country-specific amendments (France Protocol Amendment 0.1 and 0.2 and UK Protocol Amendment 0.2) were incorporated into Global Protocol Amendment 1. In addition, the Spanish Competent Authority recommended the inclusion of electrocardiogram (ECG) assessments within the study design; this was also implemented within Global Protocol Amendment 1.
    04 Mar 2016
    The protocol dated 04-Mar-2016 was amended to provide further information regarding prohibited P-glycoprotein substrate (PGP) inhibitors. Rather than specify “strong” inhibitors, all known inhibitors were excluded until further information was obtained regarding UCB5857’s PGP substrate status. To facilitate identification of known PGP inhibitors, a sample, but nonexhaustive, list of PGP inhibitors was added as a table to the protocol. In addition, the definition of the Pharmacokinetic Set (PKS) was amended to correct an error. Previously the PK Set was incorrectly defined as a subset of the Full Analysis Set (FAS) when it should have been a subset of the Safety Set where subjects were assigned to the actual treatment received rather than their randomized treatment.
    24 Jul 2016
    The protocol dated 24-Jul-2016 was amended as an urgent safety measure to include potential drug-induced liver injury (PDILI)-related exclusion criteria, withdrawal criteria, and guidance for the management of such cases. Cases of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) had been observed in 3 subjects receiving UCB5857 in ongoing studies, including 2 subjects in SS0004, and 1 subject in APD001 (open-label study of UCB5857 in subjects with activated phosphoinositide 3 kinase [PI3K] delta syndrome). All available blinded clinical data for these cases were medically assessed and in addition, all available data from other subjects in these ongoing studies were reviewed to identify any other potential cases of interest, but no other clinically relevant elevations in aminotransferases or other hepatobiliary laboratory values were noted. UCB considered that from the currently available information, there was a possible causal association of UCB5857 with increased aminotransferases. Consequently, additional risk minimization and pharmacovigilance measures were implemented in the protocol in order to safeguard study subjects against any possible liver injury caused by UCB5857. Additionally, and unrelated to the main purpose of the amendment, further guidance was provided on suspected transmission of an infectious agent via a medicinal product in alignment with UCB’s updated procedures.
    05 Apr 2017
    The rationale for this substantial protocol amendment dated 05-Apr-2017 was to modify the restriction regarding PGP inhibitors and remove the table of PGP inhibitors from the protocol based on newly available nonclinical data. In addition, procedures for assessment and management of Tuberculosis (TB) were added in order to comply with the UCB policy applied to all UCB-Sponsored studies (excluding noninterventional studies) that included subjects with immunological diseases, who were at increased risk of TB infection either associated with the investigational drug, underlying disease, concomitant treatments, or other medical or sociological factors. Updates to the interim analysis section were made to include text stating that an interim analysis for futility may be performed.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    27 Sep 2017
    After reviewing the feasibility and projected completion date, the Sponsor has made the decision to stop the study early. The interim analysis which was conducted per protocol indicated that the study was not futile and the safety profile of seletalisib has not changed.
    -

    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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