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   44334   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:
    A phase I pharmacokinetic and safety study of tocilizumab (TCZ) in patients less than 2 years old with active systemic juvenile idiopathic arthritis (sJIA)

    Summary
    EudraCT number
    		 2015-000435-33
    Trial protocol
    		 DE   HU   BE   ES   PL   GB   FR  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    12 Feb 2017
    First version publication date
    12 Feb 2017
    Other versions
    		 v2 , v3

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NP25737
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01455701
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F.Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Trial Information Support Line-TISL, F.Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    Trial Information Support Line-TISL, F.Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    28 Jul 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jul 2016
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the pharmacokinetics of Tocilizumab (TCZ) over 12 weeks in patients less than 2 years of age with sJIA.
    Protection of trial subjects
    The investigator will ensure that this study is conducted in full conformance with the principles of the “Declaration of Helsinki” or with the laws and regulations of the country in which the research is conducted, whichever affords the greater protection to the individual.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jun 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Argentina: 1
    Country: Number of subjects enrolled
    United States: 5
    Worldwide total number of subjects
    11
    EEA total number of subjects
    5
    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)
    11
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    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
    		 -

    Pre-assignment
    Screening details
    		 Patients whose guardian has given written informed consent underwent a thorough screening examination between -21 and -1 days before the start of the study. During the screening visit(s), inclusion/exclusion criteria were checked, a medical examination was performed.

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

    Arms
    Arm title
    		 12 mg/kg TCZ infusions
    Arm description
    		 Patients received tocilizumab 12 mg/kg by intravenous infusion every 2 weeks for a total of 6 infusions.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tocilizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Tocilizumab (200 mg/10 mL) was administered by intravenous infusion every two weeks.

    Number of subjects in period 1
    		12 mg/kg TCZ infusions
    Started
    11
    Completed
    7
    Not completed
    4
         Adverse event, non-fatal
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    12 weeks treatment period
    Reporting group description
    		 Patients received 12 mg/kg TCZ infusions every two weeks for 12 weeks

    Reporting group values
    		 12 weeks treatment period Total
    Number of subjects
    		 11 11
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 11 11
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 0 0
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 15.9 ( 4 ) -
    Gender categorical
    Units: Subjects
        Female
    		 7 7
        Male
    		 4 4

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    12 mg/kg TCZ infusions
    Reporting group description
    		 Patients received tocilizumab 12 mg/kg by intravenous infusion every 2 weeks for a total of 6 infusions.

    Primary: Systemic exposure (AUC 2 weeks)

    		 Close Top of page
    End point title
    		 Systemic exposure (AUC 2 weeks) [1]
    End point description
    Computed steady-state systemic exposure (AUC 2 weeks) defined as the area under the serum concentration-time profile during a dosing interval
    End point type
    Primary
    End point timeframe
    Data used for analysis were collected during visits at week 0, 2, 4, 6, 8, 10.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics only were planned for this endpoint.
    End point values
    		 12 mg/kg TCZ infusions
    Number of subjects analysed
    11
    Units: μg/mL×day
        arithmetic mean (standard deviation)
    919.2 ( 214.7 )
    No statistical analyses for this end point

    Primary: Systemic exposure (Cmin)

    		 Close Top of page
    End point title
    		 Systemic exposure (Cmin) [2]
    End point description
    Systemic exposure to TCZ is evaluated in terms of computed steady-state concentration at the end of a dosing interval (Cmin)
    End point type
    Primary
    End point timeframe
    Blood samples used for analysis were collected before infusion during visits at week 0, 2, 4, 6, 8, 10.
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics only were planned for this endpoint.
    End point values
    		 12 mg/kg TCZ infusions
    Number of subjects analysed
    11
    Units: μg/mL
        arithmetic mean (standard deviation)
    38.2 ( 12.9 )
    No statistical analyses for this end point

    Primary: Systemic exposure (Cmax)

    		 Close Top of page
    End point title
    		 Systemic exposure (Cmax) [3]
    End point description
    Systemic exposure to TCZ is evaluated in terms of computed steady-state maximum observed serum concentration post infusion (Cmax)
    End point type
    Primary
    End point timeframe
    Blood samples used for analysis were collected after infusion during visits at week 0, 4, 10.
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics only were planned for this endpoint.
    End point values
    		 12 mg/kg TCZ infusions
    Number of subjects analysed
    11
    Units: μg/mL
        arithmetic mean (standard deviation)
    276.1 ( 45.6 )
    No statistical analyses for this end point

    Secondary: Incidence of Adverse Events

    		 Close Top of page
    End point title
    		 Incidence of Adverse Events
    End point description
    Categorized serious and non serious adverse events (AEs) are reported. Detailed listing of AEs is provided in the AEs section.
    End point type
    Secondary
    End point timeframe
    Adverse Events were reported throughout the entire study period.
    End point values
    		 12 mg/kg TCZ infusions
    Number of subjects analysed
    11
    Units: Number of patients
        AE with fatal outcome
    0
        Serious AE
    3
        Serious AE leading to withdrawal
    3
        Serious AE leading to dose modification
    0
        Related Serious AE
    3
        AE leading to withdrawal
    4
        AE leading to dose modification
    1
        Related AE
    6
        Related AE leading to withdrawal
    4
        Related AE leading to dose modification
    1
        Total number of patients with at least one AE
    10
        Total number of events
    32
        Total number of deaths
    0
        Total number of patients withdrawn due an AE
    4
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All serious and non-serious Adverse Events are reported throughout the entire study period.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19
    Reporting groups
    Reporting group title
    12 mg/kg TCZ infusions
    Reporting group description
    		 Patients received tocilizumab 12 mg/kg by intravenous infusion every 2 weeks for a total of 6 infusions.

    Serious adverse events
    		 12 mg/kg TCZ infusions
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 11 (27.27%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    2 / 11 (18.18%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    Urticaria
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Juvenile idiopathic arthritis
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Hand−foot−and−mouth disease
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 12 mg/kg TCZ infusions
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 11 (72.73%)
    Investigations
    Transaminases increased
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Thrombocytopenia
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    General disorders and administration site conditions
    Injection site reaction
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    2 / 11 (18.18%)
         occurrences all number
    2
    Chapped lips
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Dental caries
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Allergic respiratory symptom
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    2 / 11 (18.18%)
         occurrences all number
    2
    Dermatitis
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    2 / 11 (18.18%)
         occurrences all number
    2
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 11 (36.36%)
         occurrences all number
    4
    Ear infection
         subjects affected / exposed
    2 / 11 (18.18%)
         occurrences all number
    2
    Nasopharyngitis
         subjects affected / exposed
    2 / 11 (18.18%)
         occurrences all number
    2
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Hypercalcaemia
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1
    Hyperlipidaemia
         subjects affected / exposed
    1 / 11 (9.09%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Oct 2011
    Removal of sampling for anti-TCZ antibody, TCZ PK and sIL-6R at Week 18
    30 Jan 2012
    Steroid tapering not longer mandated to remain stable for 6 weeks
    29 Oct 2014
    Change of the time between diagnosis of sJIA and treatment with biologics from a 3-month delay to a 1-month delay
    01 Jun 2015
    Clarification that previous history of significant allergic or infusion reactions to any of the excipients listed in TCZ product labeling documents is part of this exclusion criterion No4.
    10 Feb 2016
    Clarification that inclusion criterion 3 was intended to refer to the 1 month period of symptoms subsequent to the diagnosis of sJIA

    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-Fri May 02 17:20:21 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA