Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

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

    The EU Clinical Trials Register currently displays   44335   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Multicenter, double-blind, placebo-controlled, randomized withdrawal trial with Tadekinig alfa (r-hIL-18BP) in patients with IL-18 driven monogenic autoinflammatory conditions: NLRC4 mutation and XIAP deficiency

    Summary
    EudraCT number
    		 2018-003297-27
    Trial protocol
    		 DE  
    Global end of trial date
    31 Oct 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    17 May 2024
    First version publication date
    17 May 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NLRC4/XIAP.2016.001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03113760
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    AB2 Bio Ltd.
    Sponsor organisation address
    EPFL Innovation Park, Building B, 4th floor, Lausanne, Switzerland, 1015
    Public contact
    Eduardo Schiffrin, AB2 Bio Ltd., 0041 216940043, eduardo.schiffrin@ab2bio.com
    Scientific contact
    Eduardo Schiffrin, AB2 Bio Ltd., 0041 216940043, eduardo.schiffrin@ab2bio.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
    31 Oct 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Oct 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    31 Oct 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - To assess clinical efficacy of Tadekinig alfa in monogenic autoinflammatory diseases with ongoing inflammation and deleterious mutations of NLRC4-MAS or XIAP - To assess laboratory/biological evidence of efficacy
    Protection of trial subjects
    Patient safety and comfort were guiding principles for this clinical trial with Tadekinig alfa. The following measures have been defined in the study protocol: 1. In order to enhance subjects’ compliance and avoid subjects’ discomfort, local skin treatment were proposed to the parents/patients to mitigate local inflammatory reactions. 2. Collected blood volumes were taking into account the maximum limits for certain age groups. 3. Emergency cards with relevant data on the IMP and clinical trial including the contact data for availability in case of emergencies were provided to the patients.
    Background therapy
    		 N/A
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    21 Jul 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
    Canada: 3
    Country: Number of subjects enrolled
    United States: 11
    Country: Number of subjects enrolled
    Germany: 1
    Worldwide total number of subjects
    15
    EEA total number of subjects
    1
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    1
    Infants and toddlers (28 days-23 months)
    4
    Children (2-11 years)
    6
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment in 11 sites in USA, Canada and Germany

    Pre-assignment
    Screening details
    		 A total of 24 patients were screened in the study. 8 patients were screening failures. 1 patient was a screening failure and was re-enrolled upon next disease flare with subsepquent patient number (counted twice for consistency in total number of patients above).

    Period 1
    Period 1 title
    Initial 18 week Treatment - SAOL/RDBPC
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Tadekinig alfa SAOL
    Arm description
    		 Including patients treated with Tadekinig alfa from randomized double-blind placebo controlled phase (RDBPC) up to protocol version 3 and from single arm open-label phase (SAOL) from protocol version 4 and subsequent amendments. Both populations had the same treatment schedule and are analysed together in the final analysis.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tadekinig alfa
    Investigational medicinal product code
    Other name
    r-hIL-18BP
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 mg/kg s.c. every 2 days ± 5 hours

    Arm title
    		 Placebo RDBPC
    Arm description
    		 Including patients from randomized double-blind placebo controlled phase (RDBPC) up to protocol version 3 randomized to placebo treatment.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Equivalent volume of Placebo s.c. every 2 days ± 5 hours

    Number of subjects in period 1
    		Tadekinig alfa SAOL Placebo RDBPC
    Started
    14
    1
    Completed
    10
    0
    Not completed
    4
    1
         Consent withdrawn by subject
    2
    -
         Adverse event, non-fatal
    1
    -
         Disease relapse
    1
    1
    Period 2
    Period 2 title
    Randomized Withdrawal Phase
    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
    		 Tadekinig alfa
    Arm description
    		 Active treatment arm in Randomized Withdrawal Phase
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tadekinig alfa
    Investigational medicinal product code
    Other name
    r-hIL-18BP
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    2 mg/kg s.c. every 2 days ± 5 hours

    Arm title
    		 Placebo
    Arm description
    		 Placebo treatment arm in Randomized Withdrawal Phase
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Equivalent volume of Placebo s.c. every 2 days ± 5 hours

    Number of subjects in period 2
    		Tadekinig alfa Placebo
    Started
    5
    5
    Completed
    5
    5

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Initial 18 week Treatment - SAOL/RDBPC
    Reporting group description
    		 Patients receiving active treatment with Tadekinig alfa (14) or Placebo (1) during the first 18 weeks

    Reporting group values
    		 Initial 18 week Treatment - SAOL/RDBPC Total
    Number of subjects
    		 15 15
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 1 1
        Infants and toddlers (28 days-23 months)
    		 4 4
        Children (2-11 years)
    		 6 6
        Adolescents (12-17 years)
    		 4 4
        Adults (18-64 years)
    		 0 0
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 4 4
        Male
    		 11 11

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Tadekinig alfa SAOL
    Reporting group description
    		 Including patients treated with Tadekinig alfa from randomized double-blind placebo controlled phase (RDBPC) up to protocol version 3 and from single arm open-label phase (SAOL) from protocol version 4 and subsequent amendments. Both populations had the same treatment schedule and are analysed together in the final analysis.

    Reporting group title
    Placebo RDBPC
    Reporting group description
    		 Including patients from randomized double-blind placebo controlled phase (RDBPC) up to protocol version 3 randomized to placebo treatment.
    Reporting group title
    Tadekinig alfa
    Reporting group description
    		 Active treatment arm in Randomized Withdrawal Phase

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo treatment arm in Randomized Withdrawal Phase

    Primary: Time to first occurrence of disease reactivation (including full and partial disease reactivation) during the RW phase

    		 Close Top of page
    End point title
    		 Time to first occurrence of disease reactivation (including full and partial disease reactivation) during the RW phase
    End point description
    Median time to first occurrence of DR was 2.71 weeks for the placebo group, and was not applicable in the TA group due to the small number of patients (2 patients) with a disease reactivation. Therefore, 25th Percentile was entered below for results. Time to 80% event free was 1.93 weeks for placebo and 7.57 weeks for Tadekinig alfa.
    End point type
    Primary
    End point timeframe
    Time to First Occurrence of Disease Reactivation during the RW Phase (up to 16 weeks)
    End point values
    		 Tadekinig alfa Placebo
    Number of subjects analysed
    5
    5
    Units: Weeks
        median (confidence interval 95%)
    11.43 (4.0 to 11.43)
    2.29 (1.86 to 2.71)
    Attachments
    		 2018-003297-27_Primary Endpoint KaplanMeier
    Statistical analysis title
    		 Primary per protocol analysis
    Statistical analysis description
    Primary analysis adhering to per protocol criteria.
    Comparison groups
    Tadekinig alfa v Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.1492
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 2.11
    Notes
    [1] - Tadekinig alfa is compared to placebo using the log rank test. Kaplan-Meier (KM) estimates of the distribution of time-to-event are summarized and graphed by treatment group. Greenwood’s formula is used to estimate the standard error of the KM statistic. The primary analysis endpoint is tested at a 2-sided alpha level of 0.05.
    Statistical analysis title
    		 Sensitivity analysis for patient 14-001 (no DR) [2]
    Statistical analysis description
    Patient 14-001 was patient with XIAP-deficiency and frequent flares (>60) requiring increased corticosteroids prior to enrolment. Disease reactivation criteria in RW phase were met by transient abdominal symptoms of pain/colic & diarrhea and CRP exactly twice upper limit of normal; no additional usual disease manifestations observed. Disease reactivation was self-resolving without steroids, as opposed to prior flares. Sensitivity analysis reasseses this patient as not flaring in RW phase.
    Comparison groups
    Tadekinig alfa v Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.0494
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 -
    Notes
    [2] - A low or upper value for the confidence interval may be missing. Values for both the lower and upper limit are expected to be provided with a 2-sided confidence interval.
    Justification: The upper limit is reported as not applicable and therefore left empty.

    Secondary: Response to therapy (including complete response and partial response) in the SAOL phase from Week 10 onwards and observed at least at 2 consecutive visits at least 2 weeks apart during the SAOL phase

    		 Close Top of page
    End point title
    		 Response to therapy (including complete response and partial response) in the SAOL phase from Week 10 onwards and observed at least at 2 consecutive visits at least 2 weeks apart during the SAOL phase [3]
    End point description
    Key secondary efficacy endpoint; patients who discontinued prior to Week 10 are non-responders.
    End point type
    Secondary
    End point timeframe
    18 week initial treatment phase for patients with active treatment with Tadekinig alfa
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Patients
    10
    No statistical analyses for this end point

    Secondary: Best Response to Therapy During the SAOL Phase

    		 Close Top of page
    End point title
    		 Best Response to Therapy During the SAOL Phase [4]
    End point description
    Complete response - No major end organ damage (=objective mAIDAI components) - No systemic inflammation - Discontinuation of immunosuppressive therapy (systemic steroids or other) Partial Response - Resolution of at least 50% of major end organ damage - and 50% of markers normalized or discontinuation of immunosuppressive therapy (systemic steroids or other) Disease improvement - Resolution of at least 1 major end-organ or normalization or 50% decrease of marker - No dose increase of immunosuppressive therapies
    End point type
    Secondary
    End point timeframe
    18 week initial treatment phase with Tadekinig alfa
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Patients
        Complete response
    1
        Partial response
    10
        Disease improvement
    3
        No improvement
    0
    No statistical analyses for this end point

    Secondary: Duration of Response to Therapy during the SAOL Phase

    		 Close Top of page
    End point title
    		 Duration of Response to Therapy during the SAOL Phase [5]
    End point description
    Duration of response to therapy is only assessed for patients with a complete or partial response to therapy during SAOL as defined in the statistical analysis plan and is defined as the time from first assessment indicating partial or complete response until the time of subsequent disease reactivation. The median duration of response to therapy during the SAOL Phase was not estimable, due to the small percentage of patients who experienced a disease reactivation. Minimum duration of response was 2.1 weeks; maximum duration of response was 19.0 weeks.
    End point type
    Secondary
    End point timeframe
    18 weeks in the initial treatment phase with Tadekinig alfa
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Weeks
        median (confidence interval 95%)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Disease Reactivation Rate per Week during the SAOL Phase

    		 Close Top of page
    End point title
    		 Disease Reactivation Rate per Week during the SAOL Phase [6]
    End point description
    Number of disease reactivations for treated patients The mean disease reactivation rate per week was 0.0 (with SD 0.09) and min/max of 0.0/0.3.
    End point type
    Secondary
    End point timeframe
    18 weeks initial treatment phase with Tadekinig alfa
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Disease reactivations
        0 Disease Reactivations
    11
        1 Disease Reactivations
    1
        2 Disease Reactivations
    2
        3 Disease Reactivations
    0
        >3 Disease Reactivations
    0
    No statistical analyses for this end point

    Secondary: Treatment failures (i.e. patients who experience at least one disease reactivation) during the SAOL phase

    		 Close Top of page
    End point title
    		 Treatment failures (i.e. patients who experience at least one disease reactivation) during the SAOL phase [7]
    End point description
    Treatment failures were defined as patients who experienced at least 1 disease reactivation. Disease reactivation includes full or partial disease reactivation after the first assessment indicating partial or complete response during the SAOL phase as defined in the statistical analysis plan.
    End point type
    Secondary
    End point timeframe
    18 week initial treatment phase with Tadekinig alfa
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Patients
    3
    No statistical analyses for this end point

    Secondary: Change from Baseline in Serum Ferritin during the SAOL Phase by Visit

    		 Close Top of page
    End point title
    		 Change from Baseline in Serum Ferritin during the SAOL Phase by Visit [8]
    End point description
    End point type
    Secondary
    End point timeframe
    18 week initial treatment phase with tadekinig alfa
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Serum Ferritin (ng/mL)
    arithmetic mean (standard deviation)
        Change from Baseline to Week 1
    -3333.1 ( 7008 )
        Change from Baseline to Week 2
    -6061.1 ( 13168.11 )
        Change from Baseline to Week 3
    -5488.0 ( 12882.6 )
        Change from Baseline to Week 4
    -1970.6 ( 8216.18 )
        Change from Baseline to Week 8
    -5761.1 ( 10439.98 )
        Change from Baseline to Week 12
    -7032.6 ( 14345.88 )
        Change from Baseline to Week 18
    -8558.7 ( 15700.51 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in CRP during the SAOL Phase by Visit

    		 Close Top of page
    End point title
    		 Change from Baseline in CRP during the SAOL Phase by Visit [9]
    End point description
    End point type
    Secondary
    End point timeframe
    18 weeks initial treatment pahse with Tadekinig alfa
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: CRP (mg/dL)
    arithmetic mean (standard deviation)
        Change from Baseline to Week 1
    -2.35 ( 3.364 )
        Change from Baseline to Week 2
    -1.46 ( 5.736 )
        Change from Baseline to Week 3
    -2.53 ( 4.339 )
        Change from Baseline to Week 4
    -2.26 ( 3.813 )
        Change from Baseline to Week 8
    -2.04 ( 4.817 )
        Change from Baseline to Week 12
    -2.21 ( 4.730 )
        Change from Baseline to Week 18
    -2.28 ( 4.279 )
    No statistical analyses for this end point

    Secondary: Intensity of Disease Reactivations: Change from Baseline in mAIDAI Total Score in the SAOL phase

    		 Close Top of page
    End point title
    		 Intensity of Disease Reactivations: Change from Baseline in mAIDAI Total Score in the SAOL phase [10]
    End point description
    The mAIDAI (modified autoinflammatory disease activitiy index) is an assessment of global disease activity that measures 14 different components for disease as either absent (0 points) or present (2 points for Uveitis 3+/4+ and 1 point for all other symptoms) at each visit. The mAIDAI total score is the sum of the points assigned across all components and ranges from 0 to 15, with a higher score indicating more severe disease activity.
    End point type
    Secondary
    End point timeframe
    18 week initial treatment phase with Tadekinig alfa
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: mAIDAI
    arithmetic mean (standard deviation)
        Change from Baseline to Week 1
    -2.0 ( 1.62 )
        Change from Baseline to Week 2
    -2.6 ( 1.45 )
        Change from Baseline to Week 3
    -2.6 ( 1.28 )
        Change from Baseline to Week 4
    -2.5 ( 1.22 )
        Change from Baseline to Week 8
    -3.1 ( 1.73 )
        Change from Baseline to Week 12
    -3.5 ( 1.37 )
        Change from Baseline to Week 18
    -3.9 ( 0.74 )
    Attachments
    		 2018-003297-27_Secondary Endpoint mAIDAI in SAOL
    No statistical analyses for this end point

    Secondary: Change from Baseline in PGA Symptom Severity Score during the SAOL Phase

    		 Close Top of page
    End point title
    		 Change from Baseline in PGA Symptom Severity Score during the SAOL Phase [11]
    End point description
    The PGA (Physician Global Assessment) assesses the severity of disease-related (auto-inflammatory) symptoms by selecting an integer score from 0 (no symptoms) to 10 (highest severity of symptoms possible).
    End point type
    Secondary
    End point timeframe
    18 week initial treatment phase with Tadekinig alfa
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Physician Global Assessment
    arithmetic mean (standard deviation)
        Change from Baseline to Week 1
    -2.8 ( 2.19 )
        Change from Baseline to Week 2
    -3.7 ( 2.43 )
        Change from Baseline to Week 3
    -4.0 ( 2.11 )
        Change from Baseline to Week 4
    -3.2 ( 2.52 )
        Change from Baseline to Week 8
    -4.8 ( 2.42 )
        Change from Baseline to Week 12
    -5.1 ( 2.39 )
        Change from Baseline to Week 18
    -5.8 ( 2.10 )
    Attachments
    		 2018-003297-27_Secondary Endpoint PGA in SAOL
    No statistical analyses for this end point

    Secondary: Resolution of individual disease components during SAOL phase, if present at Baseline

    		 Close Top of page
    End point title
    		 Resolution of individual disease components during SAOL phase, if present at Baseline [12]
    End point description
    Resolution of Individual mAIDAI Components during the SAOL phase from Baseline to Week 18/early termination. Number displays percentage of patients with resolution of individual disease component at Week 18 or early termination visit based on the number of patients with a baseline assessment for the component of interest.
    End point type
    Secondary
    End point timeframe
    18 weeks initial treatment phase with Tadekinig alfa
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Patients
        Fever
    100
        Abdominal Pain/Colic
    80
        Nausea/Vomiting
    87
        Diarrhea
    77
        Transaminitis
    30
        Organomegaly
    54
        Rash
    75
        Uveitis
    100
        Arthralgia
    100
        Arthritis
    0
        Cytopenia
    20
    No statistical analyses for this end point

    Secondary: Change in Patient/Caregiver Qualitative Evaluation of Health Status in SAOL phase

    		 Close Top of page
    End point title
    		 Change in Patient/Caregiver Qualitative Evaluation of Health Status in SAOL phase [13]
    End point description
    The Sum of individual disease-related symptoms score is the sum of (x) individual symptom scores within domain each ranging from 0 (None) to 5 (Very severe): general wellbeing (5), gastrointestinal (7), musculoskeletal (5), skin (2), eye (2), central nervous system (3), and lymphatic (2). Patient/Caregiver Qualitative Evaluation of Health Status was implemented in protocol version 6; thus only completed by 5 patients.
    End point type
    Secondary
    End point timeframe
    18 weeks initial treatment phase with Tadekinig alfa
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    5
    Units: Individual disease-related symptom score
    arithmetic mean (standard deviation)
        Mean at Baseline
    40.5 ( 7.78 )
        Mean at Week 18
    7.6 ( 8.08 )
    No statistical analyses for this end point

    Secondary: Hospitalizations during the SAOL Phase

    		 Close Top of page
    End point title
    		 Hospitalizations during the SAOL Phase [14]
    End point description
    Hospitalization at SAOL Baseline was any hospitalization prior to the first dose of study drug during the SAOL Phase. Subsequent Hospitalizations during SAOL Phase included any additional hospitalization after study drug administation.
    End point type
    Secondary
    End point timeframe
    18 week initial treatment with with Tadekinig alfa
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Patients
        Patients not Hospitalized at SAOL Baseline
    6
        Patients Hospitalized at SAOL Baseline
    8
        No Subsequent Hospitalizations during SAOL
    10
        1 Subsequent Hospitalization during SAOL
    1
        2 Subsequent Hospitalizations during SAOL
    2
        3 or more Subsequent Hospitalizations during SAOL
    1
    No statistical analyses for this end point

    Secondary: Change from Baseline to Week 34/ET in Serum Ferritin During the RW Phase

    		 Close Top of page
    End point title
    		 Change from Baseline to Week 34/ET in Serum Ferritin During the RW Phase
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 16 weeks randomized withdrawal phase; change from Week 18 to Week 34 or Early termination visit
    End point values
    		 Tadekinig alfa Placebo
    Number of subjects analysed
    5
    5
    Units: Serum Ferritin (ng/mL)
        arithmetic mean (standard deviation)
    -109.5 ( 167.40 )
    211.8 ( 359.10 )
    Statistical analysis title
    		 Mann-Whitney-Wilcoxon test
    Statistical analysis description
    P-values comparing change from RW Baseline among treatment groups were rank-based using the Mann-Whitney-Wilcoxon test
    Comparison groups
    Tadekinig alfa v Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0317
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Change from Baseline to Week 34/ET in CRP During the RW Phase

    		 Close Top of page
    End point title
    		 Change from Baseline to Week 34/ET in CRP During the RW Phase
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 16 weeks randomized withdrawal phase; change from Week 18 to Week 34 or Early termination visit
    End point values
    		 Tadekinig alfa Placebo
    Number of subjects analysed
    5
    5
    Units: CRP (mg/dL)
        arithmetic mean (standard deviation)
    -0.02 ( 0.199 )
    0.24 ( 1.354 )
    Statistical analysis title
    		 Mann-Whitney- Wilcoxon
    Comparison groups
    Tadekinig alfa v Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4603
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Intensity of Disease Reactivations: Change from Baseline in mAIDAI Total Score in RW Phase

    		 Close Top of page
    End point title
    		 Intensity of Disease Reactivations: Change from Baseline in mAIDAI Total Score in RW Phase
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 16 weeks randomized withdrawal phase; change from Week 18 to Week 34 or Early termination visit
    End point values
    		 Tadekinig alfa Placebo
    Number of subjects analysed
    5
    5
    Units: mAIDAI Total Score
        median (standard deviation)
    -0.4 ( 0.89 )
    1.0 ( 1.73 )
    Statistical analysis title
    		 Mann-Whitney- Wilcoxon
    Comparison groups
    Tadekinig alfa v Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.111
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Change from Baseline to Week 34/ET in PGA During the RW Phase

    		 Close Top of page
    End point title
    		 Change from Baseline to Week 34/ET in PGA During the RW Phase
    End point description
    The PGA (Physician Global Assessment) assesses the severity of disease-related (auto-inflammatory) symptoms by selecting an integer score from 0 (no symptoms) to 10 (highest severity of symptoms possible).
    End point type
    Secondary
    End point timeframe
    Up to 16 weeks randomized withdrawal phase; change from Week 18 to Week 34 or Early termination visit
    End point values
    		 Tadekinig alfa Placebo
    Number of subjects analysed
    5
    5
    Units: Physician Global Assessment
        arithmetic mean (standard deviation)
    0.4 ( 0.89 )
    2.0 ( 3.39 )
    Statistical analysis title
    		 Mann-Whitney- Wilcoxon
    Comparison groups
    Tadekinig alfa v Placebo
    Number of subjects included in analysis
    10
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.7619
    Method
    		 Wilcoxon (Mann-Whitney)
    Confidence interval

    Secondary: Change in Patient/Caregiver Qualitative Evaluation of Health Status in RW Phase

    		 Close Top of page
    End point title
    		 Change in Patient/Caregiver Qualitative Evaluation of Health Status in RW Phase
    End point description
    Change from Baseline to Week 34/ET in Sum of individual disease-related symptoms During the RW Phase The individual disease-related symptoms scores were the sum of (x) individual symptom scores within domain each ranging from 0 (None) to 5 (Very severe): general wellbeing (5), gastrointestinal (7), musculoskeletal (5), skin (2), eye (2), central nervous system (3), and lymphatic (2).
    End point type
    Secondary
    End point timeframe
    Up to 16 weeks randomized withdrawal phase; change from Week 18 to Week 34 or Early termination visit
    End point values
    		 Tadekinig alfa Placebo
    Number of subjects analysed
    3
    2
    Units: Individual disease-related symptom score
    arithmetic mean (standard deviation)
        Mean at Week 18 (start of RW phase)
    11.3 ( 8.62 )
    2.0 ( 2.83 )
        Mean at Week 34 or Early Termination
    7.7 ( 7.09 )
    46.0 ( 14.14 )
    No statistical analyses for this end point

    Secondary: Hospitalizations during the RW Phase

    		 Close Top of page
    End point title
    		 Hospitalizations during the RW Phase
    End point description
    End point type
    Secondary
    End point timeframe
    Up to 16 weeks randomized withdrawal phase; change from Week 18 to Week 34 or Early termination visit
    End point values
    		 Tadekinig alfa Placebo
    Number of subjects analysed
    5
    5
    Units: Number of Hospitalizations
    0
    0
    No statistical analyses for this end point

    Secondary: Length of Hospitalization in SAOL phase

    		 Close Top of page
    End point title
    		 Length of Hospitalization in SAOL phase [15]
    End point description
    No hospitalizations occured during the randomized withdrawal phase; thus endpoint only listed for SAOL phase.
    End point type
    Secondary
    End point timeframe
    18 weeks initial treatment phase with Tadekinig alfa
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The endpoint assesses all patients with active treatment in the initial 18 weeks treatment phase (SAOL = single arm open label phase). One patient enrolled in the early protocol version 3 started with placebo in the first treatment phase and is therefore excluded from the endpoint analysis for the SAOL phase.
    End point values
    		 Tadekinig alfa SAOL
    Number of subjects analysed
    14
    Units: Days
    arithmetic mean (standard deviation)
        Length of Baseline Hospitalization
    44.8 ( 25.57 )
        Length of Subsequent Hospitalizations in SAOL
    18.0 ( 26.7 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were monitored and recorded from the time the informed consent is signed until completion of the study (Visit 13) or premature withdrawal.
    Adverse event reporting additional description
    Day to day fluctuations of the underlying disease of interest or other pre-existing disease or conditions present or detected at the start of the study were not to be reported as separate adverse events but assessed via the modified autoinflammatory disease index (mAIDAI) at scheduled or unscheduled visits in case of a disease reactivation.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    Initial 18 week Tadekinig alfa Treatment
    Reporting group description
    		 All patients starting with active treatment during the initial 18 weeks treatment phase - Single arm open label full analysis set (SAOL-FAS)

    Reporting group title
    Initial 18 week Placebo Treatment
    Reporting group description
    		 Patients received placebo in first treatment phase under protocol version 3

    Reporting group title
    Randomized Withdrawal Phase - Active
    Reporting group description
    		 Patients receiving Tadekinig alfa during Randomized Withdrawal Phase

    Reporting group title
    Randomized Withdrawal Phase - Placebo
    Reporting group description
    		 Patients receiving Placebo during Randomized Withdrawal Phase

    Reporting group title
    Screening phase
    Reporting group description
    		 Adverse events reported prior to first dose of Tadekinig alfa or placebo.

    Serious adverse events
    		 Initial 18 week Tadekinig alfa Treatment Initial 18 week Placebo Treatment Randomized Withdrawal Phase - Active Randomized Withdrawal Phase - Placebo Screening phase
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Initial 18 week Tadekinig alfa Treatment Initial 18 week Placebo Treatment Randomized Withdrawal Phase - Active Randomized Withdrawal Phase - Placebo Screening phase
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 14 (100.00%)
    1 / 1 (100.00%)
    4 / 5 (80.00%)
    4 / 5 (80.00%)
    7 / 15 (46.67%)
    General disorders and administration site conditions
    Injection site bruising
         subjects affected / exposed
    5 / 14 (35.71%)
    0 / 1 (0.00%)
    2 / 5 (40.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    41
    0
    9
    1
    0
    Injection site erythema
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    10
    0
    1
    0
    0
    Injection site pain
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 1 (0.00%)
    2 / 5 (40.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    15
    0
    5
    0
    0
    Pyrexia
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    10
    0
    1
    3
    0
    Asthenia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    Condition aggravated
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Fatigue
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    Injection site swelling
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    4
    0
    1
    0
    0
    Hypothermia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Inflammation
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Injection site reaction
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Peripheral swelling
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Complication associated with device
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Secretion discharge
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    5
    0
    0
    0
    1
    Atelectasis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pulmonary hypertension
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Rales
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Wheezing
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 1 (0.00%)
    2 / 5 (40.00%)
    0 / 5 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    6
    0
    2
    0
    3
    Red blood cell sedimentation rate increased
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    5
    0
    0
    0
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    3
    0
    0
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 14 (14.29%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    2
    1
    0
    0
    1
    Adenovirus test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    2 / 15 (13.33%)
         occurrences all number
    1
    0
    0
    0
    3
    Coronavirus test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cytomegalovirus test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Human rhinovirus test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Interleukin-2 receptor increased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Sapovirus test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Serum ferritin increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    3 / 15 (20.00%)
         occurrences all number
    2
    0
    1
    0
    3
    Transaminases increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    1
    0
    0
    0
    2
    Weight decreased
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    1
    1
    Vital signs measurement
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    5
    1
    0
    Overdose
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Transfusion reaction
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Wrist fracture
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Cardiac disorders
    Coronary artery dilatation
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Tachycardia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Fontanelle bulging
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Headache
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    Somnolence
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    1
    0
    Lymphadenopathy
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Splenomegaly
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Eye disorders
    Ocular hypertension
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    5 / 14 (35.71%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    7
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Colitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Inflammatory bowel disease
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Haematochezia
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    5
    0
    1
    0
    0
    Abdominal pain
         subjects affected / exposed
    3 / 14 (21.43%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    6
    1
    0
    0
    0
    Abdominal distension
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Poisoning
    Additional description: Food poisoning
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Frequent bowel movements
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nausea
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Vomiting
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Teething
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Dental caries
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Mouth ulceration
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hepatobiliary disorders
    Hepatosplenomegaly
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    10
    0
    0
    8
    0
    Acne
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Alopecia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Erythema
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Ingrowing nail
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Macule
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Palmar erythema
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    5
    0
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    Back pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Groin pain
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Joint effusion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Limb discomfort
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Muscle spasms
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Osteonecrosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Osteoporosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Synovitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Infections and infestations
    Clostridium difficile colitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Coronavirus infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Epstein-Barr viraemia
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Otitis media
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Tinea infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    Localised infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    1 / 15 (6.67%)
         occurrences all number
    0
    0
    0
    0
    1
    External ear cellulitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Groin abscess
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Furuncle
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Hordeolum
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    1
    0
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Metabolism and nutrition disorders
    Hypophosphataemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Decreased appetite
         subjects affected / exposed
    0 / 14 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Fluid retention
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hepatic steatosis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 1 (100.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hypocalcaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
    0 / 15 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Feb 2017
    Protocol verison 2.0 - This first protocol amendment, resulting in Protocol version 2.0 dated 21 Feb 2017, implements some changes following FDA recommendations (Study May Proceed cover letter ref ID 4035810, dated January 3, 2017). Some suggestions as discussed during the investigator meeting were considered to allow better understanding and to further clarify the study requirements.
    07 Apr 2017
    Protocol version 3.0 - With reference to FDA correspondence dated 15 March 2017, this second protocol amendment (Protocol version 3.0 dated 07 April 2017) implements FDA' recommendation to incorporate a Randomized Withdrawal Phase after the first 18-week treatment phase (Randomized Double-Blind Placebo-Control phase) as an additional assessment of efficacy.
    02 Oct 2018
    Protocol version 4.0 - Recruitment rates for this rare genetic condition were lower than expected and after discussion with investigators the main reason for the low recruitment was the initial placebo-controlled part of the study which raises ethical concerns. Thus, the initial placebo arm of the study during the first 18-weeks treatment phase was changed to a single arm open label (SAOL) design. The subsequent 8 week randomized double blind placebo control phase remained as assessment of primary efficacy.
    17 May 2019
    Protocol version 4.1 - Minor changes in protocol in response to regulatory authority review (e.g. addition of exclusion criterion for patient with hypersensitivity towards active substance or excipients; clarification for use of permitted and prohibited conconmitant medications; addition of creatinine and glomerular filtration rate to safety laboratory parameters measured)
    29 Jan 2021
    Protocol version 5 - Following a significant delay in recruitment during the COVID-19 pandemic and following a meeting with the FDA on 17 Dec 2020, this protocol amendment (Protocol version 5.0 dated 29 Jan 2021) allows the inclusion of adult patients with NLRC4 mutation and XIAP deficiency, for which the monogenic autoinflammatory condition is not well controlled. It also specifies that patients with XIAP deficiency and an unsuccessful previous bone marrow transplantation are allowed for inclusion. Furthermore, the duration of the double-blind placebo-controlled randomized withdrawal (RW) phase is prolonged from 8 weeks to a maximum of 16 weeks with a premature stop of blinded treatment in case of a disease flare.
    03 Sep 2021
    Protocol version 6 - Following a clinical outcome assessment focused type C meeting with the FDA on 23 Jun 2021 and a scientific advice discussion meeting with the EMA on 31 Aug 2021, this protocol amendment (Protocol version 6.0 dated 03 Sep 2021) implements changes to the assessment of response to therapy and disease reactivation. The implemented changes reflect the newly gained knowledge about the disease since the initial study design and take into consideration the individual disease severity of each patient and heterogeneity of the disease. Furthermore, a questionnaire exploring the patient’s or caregiver’s evaluation of the health status at baseline and at the end of each treatment phase was implemented for all patients treated under this protocol version. Finally, the selection criteria were slightly revised to lower the hurdles for enrolment for patients in a severe disease status requiring immediate start of study drug treatment.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat May 10 01:12:14 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA