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    Clinical Trial Results:
    A phase II randomised placebo controlled double blinded trial of Interleukin 1 blockade in Acute Severe Colitis

    Summary
    EudraCT number
    		 2017-001389-10
    Trial protocol
    		 GB  
    Global end of trial date
    24 Sep 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Oct 2022
    First version publication date
    11 Oct 2022
    Other versions
    Summary report(s)
    		 IASO Protocol Version 3.0 dated 30Oct18

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IASO CCTU-0165 RG81897
    Additional study identifiers
    ISRCTN number
    		 ISRCTN43717130
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IRAS: 201505, REC Reference: 17/EE/0347, NIHR Project: EME Ref: 14/201/02
    Sponsors
    Sponsor organisation name
    Cambridge University Hospitals NHS Foundation Trust
    Sponsor organisation address
    Box 401, Cambridge Clinical Trials Unit Level 6, Coton House, Cambridge, United Kingdom, CB20QQ
    Public contact
    Carrie Bayliss, Cambridge Clinical Trials Unit, +44 (0)1223 348158, cctu@addenbrookes.nhs.uk
    Scientific contact
    Carrie Bayliss, Cambridge Clinical Trials Unit, +44 (0)1223 348158, cctu@addenbrookes.nhs.uk
    Sponsor organisation name
    Cambridge University Hospitals NHS Foundation Trust
    Sponsor organisation address
    Box 277, Addenbrooke's Hospital, Cambridge, United Kingdom, Cambridge, United Kingdom, CB20QQ
    Public contact
    Steven Kelleher, +44 (0)1223 217418, research@addenbrookes.nhs.uk, CUH NHS Foundation Trust and the University of Cambridge, +44 (0)1223 217418, research@addenbrookes.nhs.uk
    Scientific contact
    Steven Kelleher, +44 (0)1223 217418, research@addenbrookes.nhs.uk, CUH NHS Foundation Trust and the University of Cambridge, +44 (0)1223 217418, research@addenbrookes.nhs.uk
    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
    23 May 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Mar 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Sep 2021
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The aim of this trial is to compare the clinical effects of anakinra with placebo when given in addition to current standard care in patients with acute severe ulcerative colitis. The primary measure of success will be any difference in the proportion of participants in the group receiving anakinra who needed escalation to more intensive medical or surgical therapy (known as rescue therapy) by 10 days after standard treatment was started, when compared with the group of participants receiving placebo.
    Protection of trial subjects
    The TSC (Trial Steering Committee) provided overall supervision with respect to the conduct of the study. Dr Oliver Brain was the independent chairman. The ethical and safety aspects of the trial were overseen by an independent DMC which was chaired by Dr Peter Irving. DMC meetings were timed so that reports could be fed into the TSC meetings.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Nov 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 113
    Worldwide total number of subjects
    113
    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)
    0
    Adolescents (12-17 years)
    1
    Adults (18-64 years)
    106
    From 65 to 84 years
    6
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Initially 214 patients from approximately 20 UK NHS acute hospitals were planned to be recruited. However, due to futility of analysis after 100 patients had been recruited, the trial was terminated early, resulting in a total of 113 patients being recruited and analysed from May 2018 to February 2021.

    Pre-assignment
    Screening details
    		 125 patients were assessed for eligibility. 12 people failed screening due to MTWSI score being too low, not ASUC, diagnosed endoscopy, did not meet the inclusion criteria, oral steroid less than 8 weeks ago, withdrew consent, and concurrent biologic. 113 patients were randomised.

    Pre-assignment period milestones
    Number of subjects started
    		 125 [1]
    Number of subjects completed
    		 113

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Consent withdrawn by subject: 1
    Reason: Number of subjects
    		 MTWSI too low: 6
    Reason: Number of subjects
    		 Not ASUC: 1
    Reason: Number of subjects
    		 Diagnosed endoscopy: 1
    Reason: Number of subjects
    		 Did not meet inclusion criteria: 1
    Reason: Number of subjects
    		 Oral steroid less than 8 weeks ago: 1
    Reason: Number of subjects
    		 Concurrent biologic: 1
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: 125 patients were assessed for eligibility. However, due to the reasons stated, 12 failed screening, resulting in the 113 patients randomised and analysed. This is the worldwide number enrolled in the trial.
    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 The placebo group will receive an injection with the same physical appearance as Anakinra to preserve blinding. They will also receive current standard of care.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Injection
    Dosage and administration details
    Same physical appearance as the IMP. Given the same as the IMP.

    Arm title
    		 Anakinra
    Arm description
    		 Anakinra is a clear, colourless to white solution for injection which may contain some translucent-to-white particles of protein in the solution. Current standard of care will also be given.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anakinra
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Injection
    Dosage and administration details
    Initial IV dose will be 100mg, and then subsequent SC dose will be 100mg for up to 10 doses as per administration schedule.

    Number of subjects in period 1
    		Placebo Anakinra
    Started
    55
    58
    Completed
    55
    58
    Period 2
    Period 2 title
    Day 10
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 The placebo group will receive an injection with the same physical appearance as Anakinra to preserve blinding. They will also receive current standard of care.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Injection
    Dosage and administration details
    Same physical appearance as the IMP. Given the same as the IMP.

    Arm title
    		 Anakinra
    Arm description
    		 Anakinra is a clear, colourless to white solution for injection which may contain some translucent-to-white particles of protein in the solution. Current standard of care will also be given.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anakinra
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Injection
    Dosage and administration details
    Initial IV dose will be 100mg, and then subsequent SC dose will be 100mg for up to 10 doses as per administration schedule.

    Number of subjects in period 2
    		Placebo Anakinra
    Started
    55
    58
    Completed
    51
    55
    Not completed
    4
    3
         Consent withdrawn by subject
    4
    2
         Physician decision
    -
    1
    Period 3
    Period 3 title
    Day 98
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 The placebo group will receive an injection with the same physical appearance as Anakinra to preserve blinding. They will also receive current standard of care.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Injection
    Dosage and administration details
    Same physical appearance as the IMP. Given the same as the IMP.

    Arm title
    		 Anakinra
    Arm description
    		 Anakinra is a clear, colourless to white solution for injection which may contain some translucent-to-white particles of protein in the solution. Current standard of care will also be given.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Anakinra
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Injection
    Dosage and administration details
    Initial IV dose will be 100mg, and then subsequent SC dose will be 100mg for up to 10 doses as per administration schedule.

    Number of subjects in period 3
    		Placebo Anakinra
    Started
    51
    55
    Completed
    51
    54
    Not completed
    0
    1
         Physician decision
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 The placebo group will receive an injection with the same physical appearance as Anakinra to preserve blinding. They will also receive current standard of care.

    Reporting group title
    Anakinra
    Reporting group description
    		 Anakinra is a clear, colourless to white solution for injection which may contain some translucent-to-white particles of protein in the solution. Current standard of care will also be given.

    Reporting group values
    		 Placebo Anakinra Total
    Number of subjects
    		 55 58 113
    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
    Created this variable by subtracting the birth date from the randomisation date. This is the age at randomisation.
    Units: years
        arithmetic mean (standard deviation)
    		 38.6 ± 14.2 39.5 ± 15.1 -
    Gender categorical
    Female or male
    Units: Subjects
        Female
    		 25 21 46
        Male
    		 30 37 67
    Therapy with immunomodulators or oral Janus kinase inhibitors
    This was a stratification factor.
    Units: Subjects
        Yes
    		 16 18 34
        No
    		 39 40 79
    Oral corticosteroids within 8 weeks prior to first dose of IV corticosteroids
    A stratification factor.
    Units: Subjects
        Yes
    		 21 24 45
        No
    		 34 34 68
    Current smoker
    Asked if they currently smoked.
    Units: Subjects
        Yes
    		 6 8 14
        No
    		 49 50 99
    Endoscopic MAYO score
    Where available
    Units: Subjects
        One
    		 5 2 7
        Two
    		 12 16 28
        Three
    		 13 16 29
        Not available
    		 25 24 49
    EQ5D: VAS score
    Baseline score summary of the EQ5D pain score.
    Units: unknown
        arithmetic mean (standard deviation)
    		 46.4 ± 19.2 44.3 ± 19.7 -
    EQ5D: Utility score
    Baseline EQ5D score of utility.
    Units: unknown
        arithmetic mean (standard deviation)
    		 0.588 ± 0.209 0.561 ± 0.228 -
    MTWSI score
    Modified Truelove Witts severity index score at baseline.
    Units: unknown
        arithmetic mean (standard deviation)
    		 14 ± 2.25 14.3 ± 2.24 -
    CUCQ-32 score
    CUCQ-32 is a questionnaire. This is the baseline summary score.
    Units: unknown
        arithmetic mean (standard deviation)
    		 164 ± 40.3 162 ± 43.5 -
    Duration of disease prior to randomisation
    Units: year
        arithmetic mean (standard deviation)
    		 5.78 ± 7.16 5.83 ± 7.83 -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 The placebo group will receive an injection with the same physical appearance as Anakinra to preserve blinding. They will also receive current standard of care.

    Reporting group title
    Anakinra
    Reporting group description
    		 Anakinra is a clear, colourless to white solution for injection which may contain some translucent-to-white particles of protein in the solution. Current standard of care will also be given.
    Reporting group title
    Placebo
    Reporting group description
    		 The placebo group will receive an injection with the same physical appearance as Anakinra to preserve blinding. They will also receive current standard of care.

    Reporting group title
    Anakinra
    Reporting group description
    		 Anakinra is a clear, colourless to white solution for injection which may contain some translucent-to-white particles of protein in the solution. Current standard of care will also be given.
    Reporting group title
    Placebo
    Reporting group description
    		 The placebo group will receive an injection with the same physical appearance as Anakinra to preserve blinding. They will also receive current standard of care.

    Reporting group title
    Anakinra
    Reporting group description
    		 Anakinra is a clear, colourless to white solution for injection which may contain some translucent-to-white particles of protein in the solution. Current standard of care will also be given.

    Primary: Need for rescue therapy or colectomy

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    End point title
    		 Need for rescue therapy or colectomy
    End point description
    If day 10 assessments were performed, the variable would be yes if the time difference between rescue therapy and first IV corticosteroid is <10 days and they answered yes to having had medical or surgical rescue therapy. The variable would be "no" if they did not have medical or surgical rescue therapy or the time difference was >10 days. If no day 10 assessment was performed, the endpoint was missing.
    End point type
    Primary
    End point timeframe
    The endpoint is need for rescue therapy or colectomy up to day 10.
    End point values
    		 Placebo Anakinra
    Number of subjects analysed
    50
    54
    Units: People
        Yes
    13
    23
        No
    37
    31
    Statistical analysis title
    		 Logistic regression model 1
    Statistical analysis description
    The absolute risk difference will be estimated for the incidence rate of the need for medical or surgical rescue therapy within 10 days between the treatment arms. 3 separate logistic regression models will be fit. One without stratification factors. One adjusting for stratification factors, and one with the stratification factors and prior diagnosis of IBD.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.166
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.016
         upper limit
    		 0.341
    Statistical analysis title
    		 Logistic regression model 2
    Statistical analysis description
    The absolute risk difference will be estimated for the incidence rate of the need for medical or surgical rescue therapy within 10 days between the treatment arms. 3 separate logistic regression models will be fit. Model 1 without stratification factors. Model 2 adjusting for stratification factors, and model 3 with the stratification factors and prior diagnosis of IBD.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.008
         upper limit
    		 0.339
    Statistical analysis title
    		 Logistic regression model 3
    Statistical analysis description
    The absolute risk difference will be estimated for the incidence rate of the need for medical or surgical rescue therapy within 10 days between the treatment arms. 3 separate logistic regression models will be fit. Model 1 without stratification factors. Model 2 adjusting for stratification factors, and model 3 with the stratification factors and prior diagnosis of IBD.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Risk difference (RD)
    Point estimate
    0.143
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.041
         upper limit
    		 0.324

    Secondary: Colectomy within 98 days

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    End point title
    		 Colectomy within 98 days
    End point description
    If day 98 assessment was performed, the variable was "yes" if colectomy was performed and the time difference was <98 days. The variable was "no" if colectomy was not performed or the time difference was >98 days. If no day 98 assessment was performed, the value would be missing.
    End point type
    Secondary
    End point timeframe
    98 days following first IV corticosteroid.
    End point values
    		 Placebo Anakinra
    Number of subjects analysed
    50
    54
    Units: People
        Yes
    2
    6
        No
    48
    48
    Statistical analysis title
    		 Logistic regression model 1
    Statistical analysis description
    The incidence of colectomy will be compared in a logistic regression model to estimate the effect of treatment with anakinra. The log odds ratio will be estimated. Model 1 contains only treatment arm, and model 2 contains the stratification factors as well.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Log odds ratio
    Point estimate
    1.099
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.425
         upper limit
    		 3.053
    Statistical analysis title
    		 Logistic regression model 2
    Statistical analysis description
    The incidence of colectomy will be compared in a logistic regression model to estimate the effect of treatment with anakinra. The log odds ratio will be estimated. Model 1 contains only treatment arm, and model 2 contains the stratification factors as well.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Log odds ratio
    Point estimate
    1.106
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.432
         upper limit
    		 3.07

    Secondary: Time to clinical response

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    End point title
    		 Time to clinical response
    End point description
    Time to clinical response is date from the first IV corticosteroid to clinical response. Events: patients who had two consecutive days with MTWSI<10 without missing any assessments prior to the event; the date of first assessment of these two consecutive days will be used in the time to clinical response. Censoring: date of the last consecutive assessment day 0.5 if day 1 assessment was missing; patients who had two consecutive days with MTWSI<10 but with missing assessment before will be censored at the last consecutive assessment.
    End point type
    Secondary
    End point timeframe
    Date of first MTWSI assessment or last consecutive assessment.
    End point values
    		 Placebo Anakinra
    Number of subjects analysed
    53
    57
    Units: day
        number (not applicable)
    53
    57
    Attachments
    		 Kaplan-Meier curve
    Statistical analysis title
    		 Cox model
    Statistical analysis description
    Cox model for the time to clinical response containing the stratification factors and treatment group. The result for treatment group will be given.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    110
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.27 [1]
    Method
    		 Regression, Cox
    Parameter type
    		 Log hazard ratio
    Point estimate
    0.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.21
         upper limit
    		 0.77
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.25
    Notes
    [1] - For no therapy with immunomodulators, the p-value was 0.73, and for no oral corticosteroids, the p-value was 0.45

    Secondary: Time to medical or surgical rescue therapy

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    End point title
    		 Time to medical or surgical rescue therapy
    End point description
    Time to medical or surgical rescue therapy, measured according to the time after the first dose of IV corticosteroids until the time that rescue therapy occurs (using definitions as set out in primary endpoint). Data will be captured up to the same time point as the primary endpoint.
    End point type
    Secondary
    End point timeframe
    Data will be captured up to day 10 assessment.
    End point values
    		 Placebo Anakinra
    Number of subjects analysed
    50
    54
    Units: day
        number (not applicable)
    50
    54
    Attachments
    		 Kaplan-Meier curve
    Statistical analysis title
    		 Cox model
    Statistical analysis description
    For time to medical or surgical rescue therapy. The model contains the two stratification factors and treatment group. The estimate for treatment group will be presented.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.17 [2]
    Method
    		 Regression, Cox
    Parameter type
    		 Log hazard ratio
    Point estimate
    0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 1.13
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.34
    Notes
    [2] - For no therapy, the p-value was 0.16. For no oral corticosteroids, the p-value was 0.19.

    Secondary: Burden of MTWSI

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    End point title
    		 Burden of MTWSI
    End point description
    End point type
    Secondary
    End point timeframe
    The average MTWSI was assessed in a mixed model. This was meaured from baseline to day 5.
    End point values
    		 Placebo Anakinra
    Number of subjects analysed
    52
    57
    Units: unit(s)
        number (not applicable)
    52
    57
    Statistical analysis title
    		 Random effects mixed model
    Statistical analysis description
    To test the burden of MTWSI, a random effects mixed model for repeated measurements will be fitted. The fixed effects will include treatment allocation, baseline MTWSI, time of assessments (days 1-5), and an interaction between treatment allocation and time. The dependent variable will be the total MTWSI score repeated from days 1 to 5. A random intercept will be fitted to allow the average MTWSI score to be higher or lower for each individual.
    Comparison groups
    Placebo v Anakinra
    Number of subjects included in analysis
    109
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.83
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.45
         upper limit
    		 1.17
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.67

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to Day 10. Expected AEs or SAEs as follows did not require expedited reporting: - Diarrhoea/worsening diarrhoea - Abdominal pain/increased abdominal pain - Rectal pain/worsening rectal pain - Development of toxic megacolon or hypoalbuminaemia
    Adverse event reporting additional description
    Reportable SAEs/SARs were defined as any untoward medical occurrence that at any dose: - Results in death - Is life-threatening - Requires hospitalisation or prolongation of inpatients´ hospitalisation - Results in persistent or significant disability or incapacity - Is a congenital anomaly or birth defect - Is an important medical event
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Anakinra
    Reporting group description
    		 -

    Reporting group title
    Placebo
    Reporting group description
    		 -

    Serious adverse events
    		 Anakinra Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 58 (15.52%)
    10 / 55 (18.18%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Nervous system disorders
    HEADACHE
    Additional description: HEADACHE
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PARAESTHESIA
    Additional description: PARAESTHESIA
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERONEAL NERVE PALSY
    Additional description: PERONEAL NERVE PALSY
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    CHOLANGITIS SCLEROSING
    Additional description: CHOLANGITIS SCLEROSING
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    COLITIS ULCERATIVE
    Additional description: COLITIS ULCERATIVE
         subjects affected / exposed
    7 / 58 (12.07%)
    7 / 55 (12.73%)
         occurrences causally related to treatment / all
    2 / 7
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CONSTIPATION
    Additional description: CONSTIPATION
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    CLOSTRIDIUM DIFFICILE INFECTION
    Additional description: CLOSTRIDIUM DIFFICILE INFECTION
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA
    Additional description: PNEUMONIA
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Anakinra Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    13 / 58 (22.41%)
    19 / 55 (34.55%)
    Investigations
    BLOOD POTASSIUM DECREASED
    Additional description: BLOOD POTASSIUM DECREASED
         subjects affected / exposed
    2 / 58 (3.45%)
    2 / 55 (3.64%)
         occurrences all number
    2
    2
    LIVER FUNCTION TEST ABNORMAL
    Additional description: LIVER FUNCTION TEST ABNORMAL
         subjects affected / exposed
    2 / 58 (3.45%)
    1 / 55 (1.82%)
         occurrences all number
    2
    1
    Cardiac disorders
    ATRIAL FIBRILLATION
    Additional description: ATRIAL FIBRILLATION
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    Nervous system disorders
    HEADACHE
    Additional description: HEADACHE
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    NEUROPATHY PERIPHERAL
    Additional description: NEUROPATHY PERIPHERAL
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    PRESYNCOPE
    Additional description: PRESYNCOPE
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    CHEST PAIN
    Additional description: CHEST PAIN
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    NIGHT SWEATS
    Additional description: NIGHT SWEATS
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    PERIPHERAL SWELLING
    Additional description: PERIPHERAL SWELLING
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    PYREXIA
    Additional description: PYREXIA
         subjects affected / exposed
    0 / 58 (0.00%)
    3 / 55 (5.45%)
         occurrences all number
    0
    5
    Gastrointestinal disorders
    ABDOMINAL DISTENSION
    Additional description: ABDOMINAL DISTENSION
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    ABDOMINAL PAIN
    Additional description: ABDOMINAL PAIN
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    COLITIS ULCERATIVE
    Additional description: COLITIS ULCERATIVE
         subjects affected / exposed
    0 / 58 (0.00%)
    3 / 55 (5.45%)
         occurrences all number
    0
    3
    CONSTIPATION
    Additional description: CONSTIPATION
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    DYSPEPSIA
    Additional description: DYSPEPSIA
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    GASTRITIS
    Additional description: GASTRITIS
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    LOWER ABDOMINAL PAIN
    Additional description: LOWER ABDOMINAL PAIN
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    NAUSEA
    Additional description: NAUSEA
         subjects affected / exposed
    0 / 58 (0.00%)
    2 / 55 (3.64%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    COUGH
    Additional description: COUGH
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    OOROPHARYNGEAL PAIN
    Additional description: OOROPHARYNGEAL PAIN
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    HYPERHIDROSIS
    Additional description: HYPERHIDROSIS
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    RASH
    Additional description: RASH
         subjects affected / exposed
    1 / 58 (1.72%)
    3 / 55 (5.45%)
         occurrences all number
    1
    3
    Psychiatric disorders
    ANXIETY
    Additional description: ANXIETY
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    PSYCHOGENIC SEIZURE
    Additional description: PSYCHOGENIC SEIZURE
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    BACK PAIN
    Additional description: BACK PAIN
         subjects affected / exposed
    2 / 58 (3.45%)
    1 / 55 (1.82%)
         occurrences all number
    2
    1
    JOINT SWELLING
    Additional description: JOINT SWELLING
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    MUSCULSKELETAL PAIN
    Additional description: MUSCULSKELETAL PAIN
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    2
    PAIN IN EXTREMITY
    Additional description: PAIN IN EXTREMITY
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    CAMPYLOBACTER INFECTION
    Additional description: CAMPYLOBACTER INFECTION
         subjects affected / exposed
    2 / 58 (3.45%)
    0 / 55 (0.00%)
         occurrences all number
    2
    0
    EPSTEIN BARR VIRUS INFECTION
    Additional description: EPSTEIN BARR VIRUS INFECTION
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    HEPATITIS C
    Additional description: HEPATITIS C
         subjects affected / exposed
    1 / 58 (1.72%)
    0 / 55 (0.00%)
         occurrences all number
    1
    0
    ORAL CANDIDIASIS
    Additional description: ORAL CANDIDIASIS
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    SHIGELLA INFECTION
    Additional description: SHIGELLA INFECTION
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    URINARY TRACT INFECTION
    Additional description: URINARY TRACT INFECTION
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    HYPERGLYCAEMIA
    Additional description: HYPERGLYCAEMIA
         subjects affected / exposed
    0 / 58 (0.00%)
    1 / 55 (1.82%)
         occurrences all number
    0
    1
    HYPOKALEMIA
    Additional description: HYPOKALEMIA
         subjects affected / exposed
    1 / 58 (1.72%)
    1 / 55 (1.82%)
         occurrences all number
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 May 2018
    Amendment 3 - Updated protocol to v2.0 to reflect the addition of more sites in the initial phase of the trial
    18 Jan 2019
    Amendment 4 - Addition of new sites
    12 Mar 2019
    Amendment 5 - Addition of new sites
    04 Apr 2019
    Amendment 6 - Addition of new sites
    22 May 2019
    Amendment 7 - Addition of new site
    10 Jun 2019
    Amendment 8 - Addition of new site
    01 Jul 2019
    Amendment 9 - Addition of new site
    24 Sep 2019
    Amendment 10 - Addition of new site
    13 Jan 2021
    Amendment 12 - Change of PI at Cardiff site

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    23 Mar 2020
    Trial recruitment was delayed due to the COVID-19 lockdown, usually due to the reallocation of staff resources. The trial was not formally paused or restarted but this did have an impact.
    -

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

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