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    The EU Clinical Trials Register currently displays   36391   clinical trials with a EudraCT protocol, of which   5995   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).
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    EudraCT Number:2014-002715-41
    Sponsor's Protocol Code Number:P130934
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-03-27
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2014-002715-41
    A.3Full title of the trial
    KAWAKINRA study, "A phase IIa multicenter trial to assess the efficacy and safety of Anakinra in patients with intraveinous immunoglobulin-resistant Kawasaki disease"
    «Ensayo multicéntrico de fase IIa para evaluar la eficacia y seguridad de Anakinra en pacientes con enfermedad de Kawasaki resistente a la inmunoglobulina intravenosa»
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    KAWAKINRA study, "A phase IIa multicenter trial to assess the efficacy and safety of Anakinra in patients with intraveinous immunoglobulin-resistant Kawasaki disease"
    «Ensayo multicéntrico de fase IIa para evaluar la eficacia y seguridad de Anakinra en pacientes con enfermedad de Kawasaki resistente a la inmunoglobulina intravenosa»
    A.3.2Name or abbreviated title of the trial where available
    A.4.1Sponsor's protocol code numberP130934
    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.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 supportPHRC
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSANT JOAN DE DÉU
    B.5.2Functional name of contact pointprincipal investigator
    B.5.3 Address:
    B.5.3.1Street AddressNumancia, 7-13
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08029
    B.5.4Telephone number0034 932 532 140
    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. name kineret
    D. of the Marketing Authorisation holderSOBI Swedish Orphan Biovitrum AB SE-112 76 Stockholm Suède
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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 namekineret
    D.3.2Product code ATC : L04AC03
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation Yes
    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 INNanakinra
    D.3.9.2Current sponsor codeP130934
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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.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
    Anakinra treatment is expected to reduce the early and long term mortality of patients with Kawasaki Disease (KD), by a rapid and sustained effect on vascular inflammation
    el tratamiento anakinra deberia reducir la mortalidad precoz y a largo plazo de los patientes afectados por la enfermedad de kawasaki, para un efecto importante y rapido en la inflamacion vascular.
    E.1.1.1Medical condition in easily understood language
    Anakinra treatment is expected to reduce the early and long term mortality of patients with Kawasaki Disease (KD), by a rapid and sustained effect on vascular inflammation
    el tratamiento anakinra deberia reducir la mortalidad precoz y a largo plazo de los patientes afectados por la enfermedad de kawasaki, para un efecto importante y rapido en la inflamacion vascular.
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level PT
    E.1.2Classification code 10023320
    E.1.2Term Kawasaki's disease
    E.1.2System Organ Class 10047065 - Vascular disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Assess the efficacy of anakinra (IL-1R1receptor antagonist) in patients on fever with KD who fail to respond to one infusion of IVIg (standard treatment).
    Evaluar la eficacia de anakinra (antagonista del receptor R1 de IL-1) en pacientes febriles con EK que no respondieron a una infusión de IGIV (tratamiento standard).
    E.2.2Secondary objectives of the trial
    -To assess the efficacy of anakinra on disease activity
    -To assess the efficacy of anakinra on coronary lesions (eg: dilatation and aneurysm)
    -To assess the efficacy of anakinra on inflammation
    -To assess the safety and tolerability of anakinra
    -Evaluar la eficacia de anakinra sobre la actividad de la enfermedad
    -Evaluar la eficacia de anakinra sobre las lesiones coronarias (p. ej.: dilatación y aneurisma)
    -Evaluar la eficacia de anakinra sobre la inflamación
    -Evaluar la seguridad y tolerancia de anakinra
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    -inflammatory biomarkers
    -gene expression profiling
    -endothelial cell activation markers
    -antibodies against anakinra
    -biomarcadores -inflamatorios
    -perfiles de la expresión de los genes
    -marcadores de activación de células endotheliales
    -anticuerpos contra anakinra
    E.3Principal inclusion criteria
    1. Patient, male and female, ? 8 months of life and ? 18 years old,

    2. Patient ? 10 kg

    3. Patient with KD according to the American Heart Association definition for complete or incomplete KD. (Fever ? 5 days (or at least 3 days if KD with AHA criteria since the third day of fever) and ? 4 of 5 main clinical signs: modification of the extremities, polymorphic exanthema, bilateral bulbar not exudative conjunctivitis, erythema of the lips or oral cavity, and cervical lymph nodes usually unilateral > 1.5 cm in diameter. In the presence of less than 4 clinical criteria and 5 days of fever, the diagnosis of disease KD is proposed in case of coronary abnormalities (at least one dilated coronary artery with internal diameter ? 2,5 SD from the mean normalized for body surface area (Z score) as determined by echocardiography). For indicative purpose, in case of incomplete KD, other biological supportive criteria for incomplete KD can help to ensure the diagnosis: leucocytosis, elevated CRP, elevated ESR, anaemia, hyponatremia, elevated ASAT, ALAT and gGT, hyperlipidaemia.

    4. Patient who failed to respond to standard therapy of KD: e.g. Persistence or recrudescence of fever ? 38°C, 48 hours after the infusion of 2g/kg of IV Ig, The interval may be reduced to 24h after the end of the infusion if the patient is still febrile 24h after the end of the infusion.

    5. Patient, parents or legal guardian?s written informed consent is required

    6. Patient with health insurance

    7. Patient agrees to have effective contraception for the duration of participation in the research
    1. Paciente de sexo masculino o femenino, ? 8 meses y ? 18 años de edad.

    2. Paciente ? 10 kg

    3. Paciente con EK, de acuerdo con la definición de la American Heart Association para una EK completa o incompleta. (Fiebre ? 5 días o al menos 3 días si EK cumple criterios de la AHA desde el tercer día de fiebre) y ? 4 de los 5 signos clínicos principales: modificación de las extremidades, exantema polimórfico, conjuntivitis bilateral bulbar no exudativa, eritema de los labios o de la cavidad bucal, y nódulos linfáticos cervicales habitualmente unilaterales > 1.5 cm de diámetro. En presencia de menos de 4 de los criterios clínicos y de 5 días de fiebre, se propone el diagnóstico de EK en caso de anomalías coronarias (al menos una arteria coronaria dilatada de diámetro interno ? 2,5 SD de la media normalizada para la superficie corporal (puntuación Z), determinado por ecocardiografía). Con fin indicativo, en caso de KD incompleta otros criterios de apoyo biológicos pueden ayudar a confirmar el diagnóstico: leucocitosis, CRP elevada, ESR elevada, anemia, hiponatremia, ASAT, ALAT y gGT elevadas, hiperlipidemia.

    4. Paciente que no responde a un tratamiento standard de EK: p. ej., persistencia o recrudescencia de fiebre ? 38°C 48 horas después de la infusión de 2g/kg de IG IV. El intervalo puede reducirse a 24h después del término de la infusión si el paciente sigue febril 24h después del término de la infusión.

    5. Es indispensable el consentimiento informado y escrito del paciente, sus padres o responsables legales.

    6. Paciente con seguro de salud.

    7. Paciente que acepta mantener una contracepción eficaz durante su participación en la investigación.
    E.4Principal exclusion criteria
    1. Preterm and neonates, pregnancy (+?-hCG if appropriate)

    2. Patients suspected with another diagnosis

    3. Patients with overt concomitant bacterial infection

    4. Patients previously treated with steroids or/and another biotherapy

    5. Patients with any type of immunodeficiency or cancer

    6. Patients with increased risk of Tuberculosis (TB) infection

    7. Recent tuberculosis infection or with active TB

    8. Close contact with a patient with TB

    9. Patients recently arrived less than 3 months from a country with high prevalence of TB

    10. A chest radiograph suggestive of TB

    11. Patients with end stage renal disease: NKF stages ?4; eGFR?29mL/min/1.73 m2 or diabetes mellitus or neutropenia <1500/mm3 or liver failure

    12. Hypersensitivity to the active substance or to any of the excipients (citric acid and anhydrous; sodium chloride disodium edetate dehydrate polysorbate 80; sodium hydroxide; water for injections)

    13. Patient already included in a biomedical research other than observational (e.g.; cohort, registry)
    1. Prematuros y neonatos, embarazo (+?-hCG si corresponde)

    2. Pacientes en que se sospecha otro diagnóstico

    3. Pacientes con infección bacteriana declarada concomitante

    4. Pacientes previamente tratados con esteroides y/u otra bioterapia

    5. Pacientes con cualquier tipo de inmunodeficiencia o cáncer

    6. Pacientes con riesgo mayor de infección tuberculosa (TB)

    7. Infección tuberculosa reciente o TB activa

    8. Contacto cercano con un paciente con TB

    9. Pacientes recién llegados (menos de 3 meses) desde un país con alta prevalencia de TB

    10. Radiografía de tórax que sugiere TB

    11. Pacientes con enfermedad renal en etapa terminal: etapas NKF ?4; eGFR?29mL/min/1.73 m2 o diabetes mellitus o neutropenia <1500/mm3 o insuficiencia hepática

    12. Hipersensibilidad a la sustancia activa o a cualquier excipiente (ácido y anhídrido cítrico; cloruro de sodio; edetato bisódico deshidratado; polisorbato 80; hidróxido de sodio; agua para inyecciones)

    13. Paciente ya incluido en un estudio biomédico que no sea sólo observacional (p. ej., cohorte, registro)
    E.5 End points
    E.5.1Primary end point(s)
    The primary statistical analysis of the proportion of patients succeeding to reach a body temperature <38°C within 24 hours of treatment by anakinra (even after dose escalation if any) at d15 will be purely descriptive through proportion of patients and its Agresti-Coull confidence interval at 95%. Based on the Intent-To-Treat principle, all included patients will be taken into account.
    El analisis estadistico primirio se centrara en la proprocion de pacientes que alcanzaron une tempertura corporal < 38°C en las 24 horas despues del trazamiento con anakinra en el dia 15. (incluso despues de un aumento de la dosis si es necesario). Este analisis sera puramente descriptivo con un intervalo de confianza Agresti-Coull a 95%, basado en el principio de intencion de tratar a los pacientes, todo paciente incluido sera tomado en cuenta en el analisis
    E.5.1.1Timepoint(s) of evaluation of this end point
    at the end of the study
    al final del estudio
    E.5.2Secondary end point(s)
    Secondary analyses: proportion of patients achieving secondary endpoints and their confidence intervals at 95% in all included patients.
    Safety analyses: descriptive only on all treated patients
    Análisis secundarios: proporción de pacientes que alcanzan los objetivos finales secundarios e intervalos de confianza de 95%, incluyendo a todos los pacientes.
    Análisis de seguridad: sólo descriptivos, en todos los pacientes tratados
    E.5.2.1Timepoint(s) of evaluation of this end point
    at the end of the study
    al final del estudio
    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 No
    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 No
    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. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    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 No
    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 EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days0
    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: 25
    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. of subjects for this age range: 5
    F.1.1.5Children (2-11years) Yes
    F. of subjects for this age range: 5
    F.1.1.6Adolescents (12-17 years) Yes
    F. of subjects for this age range: 15
    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 Yes
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 25
    F.4.2.2In the whole clinical trial 25
    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)
    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 Decision2015-08-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-03-27
    P. End of Trial
    P.End of Trial StatusOngoing
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