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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42559   clinical trials with a EudraCT protocol, of which   7007   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 in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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

    Print Download

    Summary
    EudraCT Number:2013-003956-18
    Sponsor's Protocol Code Number:PREVENT-JIA
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2014-01-13
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2013-003956-18
    A.3Full title of the trial
    Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis (JIA)
    Preventie van recidieven door risico-aangepast staken van de behandeling bij juveniele idiopathische artritis (JIA)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Prevention of disease flares by risk-adapted stratification of therapy withdrawal in juvenile idiopathic arthritis (JIA)
    Preventie van recidieven door risico-aangepast staken van de behandeling bij juveniele idiopathische artritis (JIA)
    A.3.2Name or abbreviated title of the trial where available
    PREVENT-JIA
    PREVENT-JIA
    A.4.1Sponsor's protocol code numberPREVENT-JIA
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity Medical Center Utrecht
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportInterdisziplinäre Zentrum für Klinische Forschung Münster
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Medical Center Utrecht
    B.5.2Functional name of contact pointBusiness Manager
    B.5.3 Address:
    B.5.3.1Street AddressPO Box 85090, intern mail address KB 03.057.1
    B.5.3.2Town/ cityUtrecht
    B.5.3.3Post code3508 AB
    B.5.3.4CountryNetherlands
    B.5.4Telephone number31887554250
    B.5.6E-mailA.M.W.Laeven@umcutrecht.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name enbrel
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameenbrel
    D.3.2Product code EU/1/99/126/001
    D.3.4Pharmaceutical form Injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNETANERCEPT
    D.3.9.1CAS number 185243-69-0
    D.3.9.2Current sponsor codePfizer Limited
    D.3.9.3Other descriptive nameenbrel
    D.3.9.4EV Substance CodeSUB01984MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number0.6 to 0.9
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name humira
    D.2.1.1.2Name of the Marketing Authorisation holderpfizer Limited
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namehumira
    D.3.2Product code EU/1/03/256/001
    D.3.4Pharmaceutical form Injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNADALIMUMAB
    D.3.9.1CAS number 331731-18-1
    D.3.9.2Current sponsor codeAbbott Laboratories Ltd
    D.3.9.3Other descriptive namehumira
    D.3.9.4EV Substance CodeSUB20016
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number22 to 26
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name orencia
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameorencia
    D.3.2Product code EU/1/07/389/001
    D.3.4Pharmaceutical form Infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNABATACEPT
    D.3.9.1CAS number 332348-12-6
    D.3.9.2Current sponsor codeBristol-Myers Squibb Pharma EEIG
    D.3.9.3Other descriptive nameorencia
    D.3.9.4EV Substance CodeSUB20635
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number1000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name methotrexate
    D.2.1.1.2Name of the Marketing Authorisation holderSandoz B.V.
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namemethotrexate
    D.3.2Product code RVG 28636
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNmethotrexate
    D.3.9.1CAS number 0000059-05-2
    D.3.9.2Current sponsor codeSandoz B.V.
    D.3.9.3Other descriptive nameMETHOTREXATE
    D.3.9.4EV Substance CodeSUB08856MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name methotrexate
    D.2.1.1.2Name of the Marketing Authorisation holderSandoz B.V.
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMethotrexate
    D.3.2Product code RVG 104433
    D.3.4Pharmaceutical form Injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNmethotrexate
    D.3.9.1CAS number 0000059-05-2
    D.3.9.2Current sponsor codeSandoz B.V.
    D.3.9.3Other descriptive nameMETHOTREXATE
    D.3.9.4EV Substance CodeSUB08856MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/m2 milligram(s)/square meter
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number10 to 25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    juvenile idiopathic arthritis
    juveniele idiopathische artritis
    E.1.1.1Medical condition in easily understood language
    juvenile (rheumatoid) arthritis
    jeugdreuma
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level LLT
    E.1.2Classification code 10059177
    E.1.2Term Juvenile arthritis
    E.1.2System Organ Class 100000004859
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - The main hypothesis of this study is that JIA patients at risk of a flare due to subclinical inflammatory activity may be identified by analysis of the phagocyte activity marker MRP8/14. The goal is a stratification of the therapeutic approach: Maintenance therapy for patients with elevated levels of the biomarker, stop of therapy if the biomarker is low.
    - De belangrijkste hypothese van deze studie is dat JIA patiënten met een risico op een recidief als gevolg van subklinische
    ontstekingsactiviteit kunnen worden geïdentificeerd door analyse van de fagocytaire activiteit marker S100A12 en hsCRP. Het
    doel is een gestratificeerde therapeutische aanpak: Onderhoudstherapie voor patiënten met verhoogde niveaus van de
    biomarkers, stoppen van de therapie als beide biomarkers zijn laag.
    E.2.2Secondary objectives of the trial
    - The second major hypothesis of this study is that a risk-stratified decision on withdrawal of therapy is superior to a random treatment stop time point (regarding the prevention of flares).
    - An additional hypothesis is that the current definition of remission may be refined, adding “immunological remission” as a status that will be robust enough to last after discontinuing medication. Other potentially useful markers, such as the granulocyte-activation markers S100A12 or hsCRP will be analyzed.
    - De tweede belangrijke hypothese van deze studie is dat een risico-aangepast staken van de therapie superieur (met betrekking tot de preventie van recidief) is aan het stoppen van de behandeling op een tijdstip uitsluitend gebaseerd op het perspectief van de clinici.
    - Een aanvullende hypothese is dat de huidige definitie van remissie kan worden verfijnd, het toevoegen van "immunologische remissie 'als een toestand die robuust genoeg zal zijn om te persisteren na het staken van de medicatie.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients with polyarticular course of any JIA subcategory (including extended oligoarthritis and polyarticular course of systemic JIA without systemic features) will be included at first confirmation of remission on medication, i.e. after clinically documented inactive disease (no joints with active arthritis; no fever, rash, serositis, splenomegaly, or generalized
    lymphadenopathy attributable to JIA; no active uveitis; no elevation in ESR or/and CRP attributable to JIA; physician’s global assessment of disease activity indicates no disease activity) for at least 6 months. Alternatively patients can be enrolled until 12 months (+/- 6 weeks) to ensure access to the study after 6 months of inactive disease. At the time remission is documented, patients may be ONLY on non-steroidal anti-inflammatory drugs (NSAIDs) plus DMARDs and/or biologics at a stable dose. Only approved medication is allowed during the study. Steroids must have been withdrawn at least 1 month before remission is documented. Intraarticular joint injections should not have been performed 6 months before remission is documented. At inclusion into this study patients will be considered being in clinically documented remission on medication.
    Patiënten met polyarticulaire beloop van enig JIA subtype (inclusief extended oligoartritis en polyarticulair beloop van systemisch JIA zonder systemische verschijnselen) mogen worden geincludeerd bij de eerste bevestiging van remissie op medicatie, dwz na klinisch gedocumenteerde inactieve ziekte (geen gewrichten met actieve artritis, geen koorts, huiduitslag, serositis, splenomegalie, of gegeneraliseerde lymfadenopathie door JIA; geen actieve uveitis, geen verhoging van de ESR-of / en CRP door JIA; arts globale beoordeling van de ziekteactiviteit geeft aan: "geen ziekteactiviteit") gedurende ten minste 6 maanden. Als alternatief kunnen patiënten worden geincludeerd tot 12 maanden (+/- 6 weken) om toegang tot het onderzoek te waarborgen na 6 maanden inactieve ziekte. Op het moment dat remissie wordt gedocumenteerd, mogen
    patiënten ALLEEN niet-steroïdale anti-inflammatoire geneesmiddelen (NSAID's) plus DMARD en / of biologische middelen in een stabiele dosis gebruiken. Alleen goedgekeurde medicactie is toegestaan tijdens het onderzoek. Steroïden moet minstens 1 maand gestaakt zijn voordat remissie is gedocumenteerd. Intra-articulaire gewrichtsinjecties mogen niet zijn uitgevoerd 6 maanden voordat remissie is gedocumenteerd. Bij opname in deze studie worden patiënten beschouwd als zijnde in klinisch gedocumenteerd remissie op medicatie.
    E.4Principal exclusion criteria
    Patients with persistent oligoarthritis subtype or systemic JIA having systemic features (within 1 year prior to inclusion) are excluded.
    In addition, patients may not have received treatment with steroids in the month before remission is first documented or treatment with intraarticular joint injections etc. in the 6 months before remission is first documented.
    Patient with a history of uveitis or macrophage activation syndrome are excluded.
    Patients may also not be included if withdrawal of any biological drug has ever been unsuccessful in the past.
    Patiënten met persisterende oligoartritis of systemische JIA met systemische verschijnselen (binnen 1 jaar voorafgaand aan inclusie) zijn uitgesloten.
    Bovendien mogen patiënten geen behandeling met steroïden hebben gekregen in de maand voordat de remissie voor het eerst is gedocumenteerd noch behandeling met intra-articulaire gewrichtsinjecties etc. in de 6 maanden voordat remissie voor het eerst is gedocumenteerd.
    Patiënten met een voorgeschiedenis van uveitis of macrofaagactivatiesyndroom zijn uitgesloten.
    Patiënten kunnen ook niet te worden geincludeerd indien het staken van een biologisch geneesmiddel ooit gefaald heeft in
    het verleden.
    E.5 End points
    E.5.1Primary end point(s)
    Patients in whom therapy is stopped will be compared with those who continue on maintenance therapy (=the two study groups). A comparison between these arms is mandatory as the main hypothesis is that withdrawal in a subgroup of patients with low risk of flares is safe, with flare rates not higher than in patients continuing medication. The stratification will be based upon S100A12/hsCRP levels measured in serum at each visit (i.e. every 3 months). After a watch and wait phase of 6 months in inactive disease, remission is confirmed according to the standard of care and patients will be stratified to stop therapy as soon as S100A12/hsCRP levels are below a specified threshold. As long as levels are above this threshold, patients will continue with maintenance therapy because a stable remission is not established. The stratification into these arms is dynamic.
    Patiënten bij wie de behandeling wordt gestopt zullen worden vergeleken met degenen die op onderhoudstherapie blijven (= de twee studiegroepen). Een vergelijking tussen deze armen is nodig omdat de belangrijkste hypothese is dat staken in een subgroep van patiënten met een laag risico op opvlamming veilig is, met opvlammingsrisico dat niet hoger is dan bij patiënten die hun medicatie voortzetten. De stratificatie zal worden gebaseerd op S100A12/hsCRP waarden gemeten in het serum bij elk bezoek (dwz elke 3 maanden). Na een observatiefase van 6 maanden in inactieve ziekte wordt de remissie bevestigd volgens de standaard van zorg en worden patiënten gestratificeerd waarbij de medicatie gestaakt wordt zodra onder de drempel zijn. Zolang de waarden boven de drempel, zullen patiënten doorgaan met onderhoudstherapie, omdat er vermoedelijk geen stabiele remissie is gevestigd. De stratificatie in deze armen is dynamisch.
    E.5.1.1Timepoint(s) of evaluation of this end point
    after 30 months the individual has reached the end point
    na 30 maanden heeft een individu het eindpunt bereikt
    E.5.2Secondary end point(s)
    The combined flare rate of all patients in the study will be compared to cohorts from previous studies providing robust data for a flare rate of 50% after random withdrawal of therapy shown independently in several studies. As it can be expected from our trial published in JAMA that the flare rate will be only around 25% with the stratified approach, we cannot withhold the chance of this superior approach from the patients included. The choice of comparisons was established in previous studies and for this purpose the BIKER-study will be used. The rationale for the biomarker to be tested, the units, and the cut off at 700 ng/ml was established in published work.
    Documentation is performed in intervals of 3 months in a prospective manner, starting with time point 0 month = first documentation of remission on medication. (alternatively 3 or 6 months).
    The documentation is planned using the PRINTO core set criteria, as well as draft criteria for definition of remission.
    1) Patient data: Patient data will be collected as in CRFs
    2) Patient history: Diagnosis, duration of disease, date of inclusion into the study, maximum of affected joints, maximal combined medication, time point of the discontinuation of DMARD/biological, time point of relapse (if applicable), date of examination
    3) Joints: Joint with swelling, joints with limited motion, and joint pain. Joint with active arthritis is a joint with swelling not due to bony enlargement or, if no swelling is present, limitation of motion accompanied either by pain on motion and/or tenderness (16)
    4) Core set criteria: a) MD global assessment (VAS scale 0-10cm); b) patient or parental assessment (VAS scale 0-10 cm); c) functional ability (CHAQ; grade 0-3 for 8 criteria; optionally CHAQ pain at defined time points); d) number of joints with active arthritis; e) number of joints with limited range of motion; f) erythrocyte sedimentation rate (ESR)
    5) Criteria for clinical remission: a) No joints with active arthritis; b) No fever, rash, serositis, splenomegaly, or generalized
    lymphadenopathy attributable to JIA; c) No active uveitis; d) No elevation in ESR or/and CRP attributable to JIA (if both are tested, both should be normal); e) Physician’s global assessment of disease activity indicates no disease activity (i.e. less than VAS scale 1 cm)
    Clinical remission On Medication: The criteria for the first documentation of remission on medication must be met for a minimum of six continuous months and maximum one year, in order for the patient to be considered to be in a state of clinical remission on medication.
    Clinical remission Off medication: The criteria for clinical remission must be met for a minimum of 12 continuous months while off all anti-arthritis and anti-uveitis medication in order for the patient to be considered to be in a state of clinical remission off medication.
    6) Definition of flare: Occurrence of any sign of active arthritis and/or active systemic symptoms
    7) Laboratory parameters: Documentation of the erythrocyte sedimentation rate and/or standard CRP (whenever determined). In addition serum (2 ml freshly centrifuged) will be obtained and shipped to the study center. Results of the analysis will be provided to the center within 14 days to enable stratification of the patient (i.e. withdrawal or continuation of therapy)
    De gecombineerde recidiefpercentages van alle patiënten in de studie worden vergeleken met cohorten van
    eerdere studies die een recidiefrisico zagen van 50% na willekeurig staken van therapie zoals onafhankelijk aangetoond in verschillende studies. Als uit onze proef zoals kan worden verwacht en gepubliceerd in JAMA dat het recidiefrisico slechts ongeveer 25% met de gestratificeerde aanpak zal zijn, willen we niet voorbijgaan aan de kans dat deze superieure benadering van de patiënten wordt vergeleken met de data uit eerdere studies; voor dit doel zal de BIKER-studie worden gebruikt.
    Documentatie wordt uitgevoerd in intervallen van 3 maanden in een prospectieve wijze , te beginnen met tijdstip 0 maand = eerste documentatie van remissie op medicatie . (alternatief 3 of 6 maanden ) . De documentatie is gepland met de printo kerncriteria , alsmede ontwerpcriteria voor de definitie van remissie .
    1 ) Patiëntgegevens : Patiënt gegevens worden verzameld als in CRF's
    2 ) Anamnese : diagnose , duur van de ziekte , datum van opname in de studie , maximaal aangedane gewrichten , maximale
    gecombineerde medicatie , tijdstip van de stopzetting van DMARD / biologische , tijdstip van terugval ( indien van toepassing), tijdstip van het onderzoek
    3 ) Gewrichten : gewricht met zwelling , gewrichten met beperkte beweging , en gewrichtspijn . Gewrichten met actieve artritis is een gewricht met zwelling niet te wijten aan benige verbreding of, indien er geen zwelling aanwezig is, beperking van de beweging gepaard gaand met pijn op beweging en / of gevoeligheid
    4 ) Core set criteria : 1 ) Arts globale beoordeling ( VAS schaal 0 - 10cm ) ; 2 ) de patiënt of de ouders assessment ( VAS schaal 0-10 cm ) , 3 ) de functionele mogelijkheden ( CHAQ ; graad 0-3 voor 8 criteria ; optioneel CHAQ pijn op bepaalde tijdstippen ) ; 4 )aantal gewrichten met actieve artritis ; 5 ) aantal gewrichten met een beperkt bereik van de beweging ; 6 ) bezinking ( ESR )
    5 ) Criteria voor klinische remissie : 1 ) Geen gewrichten met actieve artritis ; 2 ) Geen koorts , huiduitslag , serositis ,
    splenomegalie , of gegeneraliseerde lymfadenopathie door JIA ; 3 ) Geen actieve uveitis ; 4 ) Geen verhoging van de ESR -of / en CRP door JIA ( indien beide worden getest , moeten beide normaal ) ; 5 ) Arts globale beoordeling van de ziekteactiviteit geeft aan: geen ziekte-activiteit ( dwz minder dan VAS schaal 1 cm )
    Klinische remissie OP Medicatie : De criteria voor de eerste vastlegging van remissie OP medicatie moeten ten minste zes
    aaneengesloten maanden en maximaal een jaar worden vervuld.
    Klinische remissie ZONDER medicatie : De criteria voor klinische remissie moet worden vervuld met een minimum van 12
    maanden continu terwijl er geen gebruik is van enige anti-artritis en anti-uveitis medicatie.
    6 ) Definitie van flare : Het optreden van enig teken van actieve artritis en / of actieve systemische symptomen
    7 ) Laboratoriumparameters : Documentatie van de bezinking en / of standaard CRP ( indien bepaald ) . Daarnaast wordt serum ( 2 ml vers gecentrifugeerd ) verkregen en verscheept naar het studiecentrum UKM in Duitsland. Resultaten van de analyse zullen aan het centrum in Utrecht worden verstrekt binnen 14 dagen om stratificeren van de patiënt ( dwz staken of voortzetting van de behandeling ) mogelijk te maken.
    E.5.2.1Timepoint(s) of evaluation of this end point
    after 30 months the individual has reached the end point
    na 30 maanden heeft een individu het eindpunt bereikt
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    voortzetting therapie versus staken therapie
    continuation of therapy versus withdrawal of therapy
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA3
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Germany
    Latvia
    Netherlands
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    In those who stop therapy, a follow-up of 12 months after withdrawal will apply, i.e. the last visit will be the visit at 12 months after stopping therapy. If S100A12/hsCRP stays above the threshold over the whole intervention phase, therapy will be continued during the whole intervention phase. Afterwards, they will enter the follow-up phase after 18 months. The decision to continue or stop will be left to the physician with further follow-up of 12 months.
    Bij degenen die de therapie te staken zal een follow-up van 12 maanden na staken zijn; het laatste bezoek wordt het bezoek op 12 maanden na het stoppen van de therapie. Als S100A12/hsCRP boven de drempel blijft gedurende de gehele interventiefase dan zal de therapie worden voortgezet. Pas daarna zullen zij ook in de vervolgfase (na 18 maanden) terechtkomen. De beslissing om de behandeling dan te continueren of te stoppen wordt overgelaten aan de arts met een verdere follow-up van 12 maanden.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 70
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 10
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 40
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 20
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Minors could be included in this study.
    Minderjarigen mogen meedoen aan deze studie
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state70
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 300
    F.4.2.2In the whole clinical trial 325
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The patient will be treated and observed further in our hospital, if the patient is not yet transitioned to adult rheumatology care.
    De patient zal verder in ons ziekenhuis worden behandeld en geobserveerd zolang hij/zij nog niet in de transitie is gegaan naar de afdeling volwassen reumatologie.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-01-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-04-29
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA