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   39189   clinical trials with a EudraCT protocol, of which   6420   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).
     
    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:2011-004915-22
    Sponsor's Protocol Code Number:A3921145
    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:2017-12-01
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2011-004915-22
    A.3Full title of the trial
    A LONG-TERM, OPEN-LABEL FOLLOW-UP STUDY OF TOFACITINIB FOR TREATMENT OF JUVENILE IDIOPATHIC ARTHRITIS (JIA)
    ESTUDIO ABIERTO DE SEGUIMIENTO A LARGO PLAZO DE TOFACITINIB PARA EL TRATAMIENTO DE LA ARTRITIS IDIOPÁTICA JUVENIL (AIJ)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Long-Term, Open-Label, Study for Treatment of JIA
    ESTUDIO ABIERTO A LARGO PLAZO PARA EL TRATAMIENTO DE AIJ
    A.4.1Sponsor's protocol code numberA3921145
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01513902
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/296/2017
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPfizer Inc, 235 East 42nd Street, New York, New York 10017
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPfizer Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc.
    B.5.2Functional name of contact pointClinical Trials.gov Call Center
    B.5.3 Address:
    B.5.3.1Street Address235 East 42nd Street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number+3491490 99 00
    B.5.5Fax number0013037391119
    B.5.6E-mailclinicaltrials.govcallcenter@pfizer.com
    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 XELJANZ
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.2Product code CP-690,550-10
    D.3.4Pharmaceutical form Film-coated 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 INNTofacitinib
    D.3.9.1CAS number 540737-29-9
    D.3.9.2Current sponsor codeCP-690,550-10
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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: 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 No
    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.3.2Product code CP-690,550-10
    D.3.4Pharmaceutical form Oral solution
    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 INNTofacitinib
    D.3.9.1CAS number 540737-29-9
    D.3.9.2Current sponsor codeCP-690,550-10
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 (JIA)
    ARTRITIS IDIOPÁTICA JUVENIL (AIJ)
    E.1.1.1Medical condition in easily understood language
    Juvenile Idiopathic Arthritis (formerly known as Juvenile Rheumatoid Arthritis)
    Artritis Idiopática Juvenil (anteriormente conocida como Artritis Reumatoide Juvenil)
    E.1.1.2Therapeutic area Diseases [C] - Immune System Diseases [C20]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10059176
    E.1.2Term Juvenile idiopathic arthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to determine the long term safety and tolerability of tofacitinib for treatment of the signs and symptoms of JIA.
    El objetivo principal de este estudio es determinar la seguridad y tolerabilidad a largo plazo de tofacitinib para el tratamiento de los signos y síntomas de la AIJ.
    E.2.2Secondary objectives of the trial
    The secondary objective of this study is to evaluate the persistence of efficacy of tofacitinib for treatment of the signs and symptoms of JIA.
    El objetivo secundario de este estudio es evaluar la persistencia de la eficacia de tofacitinib para el tratamiento de los signos y síntomas de la AIJ.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects eligibility should be reviewed and documented by an appropriately investigator before subjects are included in the study. All subjects must meet Inclusion Criteria 1-11 to be eligible for enrollment into the study: 1) Pediatric subjects with JIA aged from 2 to less than 18 years who met entry criteria for the qualifying/index study and in the opinion of the investigator have sufficient evidence of JIA disease activity to warrant use of tofacitinib as a DMARD. Subjects turning 18 years of age during participation in the qualifying/index study or subsequently will be eligible for participation in this study. 2) The subject has discontinued disallowed concomitant medications for the required time prior to the first dose of study drug, as defined in Appendix 1, and is taking only those concomitant medications in doses and frequencies allowed by the protocol. 3) Fertile male subjects and female subjects of childbearing potential who are, in the opinion of the investigator, sexually active and at risk for pregnancy with their partner(s) must be using a highly effective method of contraception as outlined in this protocol throughout the study and for at least 28 days after the last dose of study medication. 4) Subjects must have previously completed participation in a qualifying study of tofacitinib for the treatment of JIA. Subjects who have required earlier discontinuation of treatment in a qualifying study for reasons other than tofacitinib related serious adverse events may be eligible. 5) For subjects receiving methotrexate (MTX) treatment, MTX may be administered either orally or parenterally at doses not to exceed 25mg/week or 20 mg/m2/week, whichever is lower. Subjects taking methotrexate must be taking folic acid or folinic acid in accordance with local standards. 6) For subjects receiving an oral glucocorticoid, glucocorticoids may be administered at a maximum dose of 0.20 mg/kg/day or 10 mg/day, prednisone or equivalent, whichever is lower (intramuscular and intravenous corticosteroids are not permitted in the 4 weeks preceding the first dose of study medication and throughout the study). For subjects coming from the systemic JIA study A3921165, a higher prednisoneequivalent dose may be continued or started (doses must be 1.0 mg/kg/day up to 30 mg/day oral prednisone [or equivalent]), with the agreement of the Pfizer medical monitor. 7)For subjects receiving leflunomide treatment, leflunomide may be administered according to the following dosing scheme:10 mg every other day for subjects patients weighing less than 20 kg; 10 mg every day for subjects weighing between 20 and 40 kg,; 20 mg every day for subjects weighing over 40 kg; Or as according to local standards. 8)For subjects receiving sulfasalazine, chloroquine, or hydroxychloroquine treatment, these medications may be administered according to local standards. 9)Evidence of a personally signed and dated informed consent document with assent as appropriate indicating that the subject (or a legally acceptable representative/ parent(s)/legal guardian) has been informed of all pertinent aspects of the study. 10)Subjects who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures. 11)Subjects for whom, in the Investigator’s opinion, treatment with tofacitinib is considered clinically appropriate while also taking into consideration currently available therapies and prior response to these therapies. Subjects who enroll outside the 14 day window of the EOS Visit of their qualifying/index study must also meet Inclusion Criterion 12 to be eligible for enrollment into the study;
    Refer to Protocol
    Todos los pacientes deben cumplir los criterios de inclusión 1 a 11 para ser aptos para su inclusión en el estudio:
    1. Pacientes pediátricos con AIJ y una edad entre 2 y menos de 18 años que cumplían los criterios de selección del estudio inicial/de cualificación y, en opinión del investigador, tienen suficientes indicios de actividad de la enfermedad AIJ como para justificar el uso de tofacitinib como un FARME. Los pacientes que cumplan 18 años durante su participación en el estudio inicial/de cualificación o posteriormente serán aptos para la participación en este estudio.
    2. El paciente ha interrumpido los medicamentos concomitantes no permitidos durante el tiempo requerido antes de la primera dosis del fármaco del estudio, tal como se define en el Anexo 1 del protocolo, y está tomando únicamente aquellos medicamentos concomitantes en dosis y frecuencias permitidos en el protocolo.
    3. Los hombres fértiles y las mujeres con capacidad de concebir que, en opinión del investigador, sean sexualmente activos y presenten riesgo de embarazo de su(s) pareja(s) o propio, deben utilizar un método anticonceptivo muy eficaz, tal como se describe en este protocolo, durante todo el estudio y durante, al menos, 28 días después de la última dosis de medicación del estudio.
    4. Los pacientes deben haber finalizado previamente la participación en un estudio de cualificación de tofacitinib para el tratamiento de la AIJ. Podrán ser aptos los pacientes que hayan requerido la interrupción anticipada del tratamiento en un estudio de cualificación por motivos que no fueran acontecimientos adversos graves relacionados con tofacitinib.
    5. Para los pacientes que reciban tratamiento con metotrexato (MTX), este podrá administrarse por vía oral o parenteral a dosis que no excedan los 25 mg/semana o 20 mg/m2/semana, lo que sea menor. Los pacientes que tomen MTX deben estar tomando ácido fólico o ácido folínico de acuerdo con las normas locales.
    6. Para los pacientes que reciban un glucocorticoide oral, este podrá administrarse a una dosis máxima de 0,20 mg/kg/día o 10 mg/día, de prednisona o equivalente, lo que sea menor (no se permiten los corticosteroides intramusculares o intravenosos en las 4 semanas anteriores a la primera dosis de medicación del estudio ni durante el estudio). Para los pacientes que procedan del estudio A3921165 de AIJ sistémica, se podrá continuar o iniciar una dosis mayor de prednisona o equivalente (las dosis deben ser 1,0 mg/kg/día hasta 30 mg/día de prednisona oral [o equivalente]), con la aceptación del supervisor médico de Pfizer.
    7. Para los pacientes que reciban tratamiento con leflunomida, esta podrá administrarse de acuerdo con la siguiente pauta posológica:
    - 10 mg en días alternos para pacientes que pesen menos de 20 kg;
    - 10 mg cada día para pacientes que pesen entre 20 y 40 kg;
    - 20 mg cada día para pacientes que pesen más de 40 kg. O según las normas locales.
    8. Para los pacientes que reciban tratamiento con sulfasalazina, cloroquina o hidroxicloroquina, estos medicamentos podrán administrarse conforme a las normas locales.
    9. Constancia de un formulario de consentimiento informado, firmado y fechado personalmente, que indique que se ha informado al paciente (o a un representante legal/progenitor(es)/tutor legal) de todos los aspectos pertinentes del estudio.
    10. Pacientes dispuestos y capaces de cumplir con todas las visitas programadas, el plan de tratamiento, las pruebas analíticas y demás procedimientos del estudio.
    11. Pacientes para los cuales el tratamiento con tofacitinib se considera, en opinión del investigador, clínicamente apropiado mientras se tienen en cuenta asimismo los tratamientos disponibles en la actualidad y la respuesta previa a dichos tratamientos.
    Los pacientes que se inscriban fuera del plazo de 14 días desde la visita de FdE de su estudio inicial/de cualificación también deben cumplir el criterio de inclusión n.º 12 para ser aptos para la inclusión en el estudio:
    12. Sin indicios de infección de tuberculosis (TB) activa o TB tratada de forma inadecuada (activa o latente), que quede videnciada por todo lo siguiente:
    a. Una prueba QuantiFERON-TB Gold In-Tube negativa realizada en los 3 meses previos a la selección. Una prueba de derivado proteico purificado (purified protein derivative, PPD) negativa, con un resultado de induración <5 mm, puede sustituir a la prueba QuantiFERON-TB Gold In-Tube solamente si el laboratorio central no puede realizar la prueba o no puede determinar los resultados como positivos o negativos, y el supervisor médico de Pfizer lo autoriza caso por caso.
    b. Se recomienda una radiografía de tórax sin cambios que sugieran infección de tuberculosis (TB) activa en los 3 meses previos a la selección, y se debe realizar de acuerdo con la práctica clínica habitual local o las directrices específicas del país.
    c. Sin antecedentes de infección por TB activa o latente no tratada o tratada de forma inadecuada.
    E.4Principal exclusion criteria
    study: For subjects who enroll outside the 14 day window of the EOS Visit of their qualifying/index study (Exclusion 1-3):
    1) Blood dyscrasas, including: a. Hgb <10 g/dL or Hct <33%. b. WBC <3.0 x 109/L. c. Neutrophil count <1.2 x 109/L. d. Platelet count <100 x 109/L. e. Lymphocyte count of <0.75 x 109/L. 2) Estimated glomerular filtration rate [GFR] <40 mL/min/1.73 m2 calculated using Bedside Schwartz formula (Appendix 5) at the Screening Visit.
    3) Aspartate aminotransferase (AST) or alanine inotransferase
    (ALT) ³1.5 times the upper limit of normal or any other clinically significant laboratory abnormality. For all subjects:
    4) Persistent oligoarthritis, and undifferentiated JIA.
    5) Current or recent history of uncontrolled clinically significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, or neurological disease.
    6) History of any other rheumatic autoimmune disease, other than Sjogren's syndrome.
    7) History or current symptoms suggestive of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease. 8 ) Infections: a) Chronic infections. b) Any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within the 6 months prior to the first dose of study drug: c) Any treated infections within 2 weeks of baseline visit. (excluding those treated with topicals only) d) A subject known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus.e.History of infected joint prosthesis with prosthesis still in situ.
    9) History of recurrent (more than one episode) herpes zoster or a single episode of disseminated herpes zoster or a single episode of disseminated (both oral and gential lesions simutaneously, or widespread lesions not contaminaed to oral or gential regions alone) herpes simplex.
    10. Subjects taking potent and moderate cytochrome P450 3A4 (CYP3A4) inhibitors (Appendix 6).
    11. Subjects taking potent and moderate CYP3A4 inducers (Appendix 6). 12. Participation in studies of investigational compounds (excluding qualifying/index study with tofacitinib) within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of study drug. Subjects cannot participate in studies of other investigational compounds at any time during their participation in this study. Exposure to investigational biologics should be discussed with the Pfizer
    MedicalMonitor. 13. Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies [eg, almetuzumab (CAMPATH®), alkylating agents (eg,
    cyclophosphamide or chlorambucil), total lymphoid irradiation, etc]. Subjects who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to study baseline
    and have normal CD 19/20+ counts by FACS analysis.
    14. Pregnant or nursing females are excluded.
    15. Intramuscular or intravenous corticosteroids in the 4 weeks preceding first dose of study medication (oral cortico steroids permitted as per inclusion criterion).
    16. Subjects who have been vaccinated with live or attenuated vaccines within the 6 weeks prior to the first dose of study medication. All study participants should be up-to-date with respect to standard of care vaccinations (as defined by their country health ministry). (See Life Style Guidelines for further information regarding avoidance of
    household contacts who may be vaccinated). 17. Use of prohibited prescription or nonprescription drugs and dietary
    supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. 18. Herbal supplements must be discontinued at least 4 weeks prior to
    the first dose of study medication. 19. Subjects with a first degree relative with a hereditary immunodeficiency; IgA
    deficiency not exclusionary. 20. Subjects with a malignancy or with a history of malignancy with the exception of adequately treated or excised non-metastatic basal cell or
    squamous cell cancer of the skin or cervical carcinoma in situ.
    21. Recent (within 28 days prior to first dose of study drug) significant trauma or major surgery. 22. Unwilling or unable to comply with the Life Style Guidelines described in this
    protocol. 23. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or
    investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. See Protocol Section 4.2 for additional exclusion criteria.
    Para los pacientes que se inscriban fuera del plazo de 14 días desde la visita de FdE de su estudio inicial/de cualificación (criterios de exclusión 1 a 3):
    1. Discrasias sanguíneas, incluidas:
    a. Hgb <10 g/dl o Hct <33 %.
    b. Leucocitos <3,0 x 109/l.
    c. Recuento de neutrófilos <1,2 x 109/l.
    d. Recuento plaquetario <100 x 109/l.
    e. Recuento linfocitario <0,75 x 109/l.
    2. Tasa de filtración glomerular (TFG) estimada <40 ml/min/1,73 m2, calculada mediante la fórmula Bedside Schwartz (Anexo 5 del protocolo) en la visita de selección.
    3. Aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) 1,5 veces el límite superior de la normalidad o cualquier otra anomalía analítica clínicamente significativa.
    Para todos los pacientes:
    4. Oligoartritis persistente y AIJ indiferenciada.
    5. Presencia actual o antecedentes recientes de enfermedad renal, hepática, hematológica, gastrointestinal, endocrina, pulmonar, cardíaca o neurológica no controlada y de importancia clínica.
    6. Antecedentes de cualquier otra enfermedad autoinmune reumática, distinta del síndrome de Sjogren.
    7. Antecedentes o presencia actual de síntomas que sugieran algún trastorno linfoproliferativo, como el síndrome linfoproliferativo asociado al virus de Epstein-Barr (VEB), antecedentes de linfoma, leucemia o signos y síntomas indicativos de la presencia de una enfermedad linfática actual.
    8. Infecciones:
    a. Infecciones crónicas.
    b. Cualquier infección que requiera hospitalización o tratamiento antimicrobiano por vía parenteral, o que el investigador considere una infección oportunista, en los 6 meses anteriores a la primera dosis del fármaco del estudio.
    c. Cualquier infección tratada en las 2 semanas previas a la visita inicial (excepto aquellas tratadas solamente por vía tópica).
    d. Un paciente que se sepa que está infectado por el virus de la inmunodeficiencia humana (VIH), hepatitis B o hepatitis C.
    e. Antecedentes de prótesis articular infectada con la prótesis colocada todavía.
    9. Antecedentes de herpes zóster recurrente (más de un episodio) o un solo episodio de herpes zóster diseminado o un solo episodio de herpes simple diseminado (con lesiones orales y genitales al mismo tiempo, o lesiones extendidas que no estén limitadas a áreas solo orales o genitales).
    10. Pacientes que tomen inhibidores potentes y moderados del citocromo P450 3A4 (CYP3A4) (Anexo 6).
    11. Pacientes que tomen inductores potentes y moderados de CYP3A4 (Anexo 6).
    12. Participación en estudios de compuestos en investigación (excepto el estudio inicial/de cualificación con tofacitinib) en el plazo de 4 semanas o 5 semividas (lo que sea más largo) antes de la primera dosis de fármaco del estudio. Los pacientes no pueden participar en estudios de otros compuestos en investigación en ningún momento durante su participación en este estudio. La exposición a productos biológicos en investigación debe comentarse con el supervisor médico de Pfizer.
    13. Cualquier tratamiento previo con tratamientos/agentes que provocan un descenso de los linfocitos, no específicos de linfocitos B (p. ej., alemtuzumab [CAMPATH´âĺ], agentes alquilantes [p. ej., ciclofosfamida o clorambucilo], irradiación linfoide total, etc.). Los pacientes que han recibido rituximab u otros agentes selectivos que provocan la disminución de los linfocitos B (incluidos agentes experimentales) son aptos si no han recibido dicho tratamiento durante al menos 1 año antes del inicio del estudio y tienen recuentos normales de CD 19/20+ según análisis FACS.
    14. Las mujeres embarazadas o en periodo de lactancia están excluidas.
    15. Corticosteroides intramusculares o intravenosos en las 4 semanas anteriores a la primera dosis de medicación del estudio (los corticosteroides orales están permitidos conforme al criterio de inclusión).
    16. Pacientes que hayan sido vacunados con vacunas vivas o atenuadas en las 6 semanas previas a la primera dosis de medicación del estudio. Todos los participantes del estudio deben tener al día todas las vacunaciones estándar (definidas por el Ministerio de salud nacional). (Véase la Guía del estilo de vida del protocolo para más información sobre cómo deben evitarse los contactos en el hogar con personas que puedan estar vacunadas).
    17. Uso de fármacos de venta con o sin receta y complementos alimenticios prohibidos en los 7 días o 5 semividas (lo que sea más largo) antes de la primera dosis de medicación del estudio.
    18. Los suplementos fitoterapéuticos se deben interrumpir al menos 4 semanas antes de la primera dosis de medicación del estudio.
    19. Pacientes con un familiar de primer grado que tenga inmunodeficiencia hereditaria; el déficit de IgA no es excluyente.
    20. Pacientes con presencia o antecedentes de neoplasia maligna, a excepción del carcinoma basocelular o espinocelular de la piel no metastásico y debidamente tratado o extirpado, o el carcinoma cervicouterino in situ.
    E.5 End points
    E.5.1Primary end point(s)
    Standard laboratory safety data and adverse event (AE) reports. Body weight, height and Tanner Stages will be collected to assess growth and physical development.
    Datos analíticos habituales de la seguridad e informes de acontecimientos adversos (AA). El peso corporal, la estatura y los estadios de Tanner se obtendrán para evaluar el crecimiento y el desarrollo físico.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary end points consist of 4 items:
    1) Standard Lab Safety Data
    2) AE assessment
    3) body weight and height
    4) Tanner Stage
    Standard Lab Safety Data is performed at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 lab is collected at 6 month intervals. AE assessment is performed at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 AE assessment is completed at 6 month intervals. Body weight and height is recorded at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 body weight and height is collected at 6 month intervals. Tanner stage is assessed at Baseline and annually thereafter.
    Los puntos finales primarios consisten de 4 elementos:
    1) Datos de seguridad estándar del laboratorio
    2) Evaluación AE
    3) peso corporal y altura
    4) Etapa de Tanner
    Los datos de seguridad estándar del laboratorio se realizan en la línea de base y en los meses 1, 3, 6, 9 y 12. Durante los años de estudio se recolectan 2 a 10 muestras de laboratorio cada 6 meses. La evaluación de EA se realiza en la Línea de Base y en los Meses 1, 3, 6, 9 y 12. Durante los años de estudio se completa la evaluación AE de 2 a 10 a intervalos de 6 meses. El peso corporal y la estatura se registran en la línea de base y en los meses 1, 3, 6, 9 y 12. Durante los años de estudio se recogen 2 - 10 de peso corporal y altura cada 6 meses. La etapa de Tanner se evalúa en la línea de base y anualmente después.
    E.5.2Secondary end point(s)
    The following efficacy parameters will be assessed:
    • Physician global evaluation of disease activity at each visit.
    • Number of joints with active arthritis at each visit.
    • Number of joints with limitation of motion at each visit.
    • Index of inflammation (C reactive protein [CRP]) and Erythrocyte Sedimentation Rate [ESR]) at each visit.
    • Childhood Health Assessment Questionnaire (CHAQ) at each visit.
    • Parent's Assessment of Physical Function (CHAQ Disability Index).
    • Parent's Assessment of Child's Arthritis Pain (CHAQ Discomfort Index, Visual Analog Scale [VAS]).
    • Parent's Assessment of Overall Wellbeing (CHAQ subsection Visual Analog Scale [VAS]).
    • JIA American College of Rheumatology (ACR) response and occurrence of JIA ACR disease flare at each visit.
    • JIA American Clinical Inactive Disease status and Clinical Remission of Medication at each visit.
    • Change from baseline in Juvenile Arthritis Disease Activity Score (JADAS) 27-CRP and JADAS 27-ESR, and occurrence of JADAS minimum disease activity and inactive disease at each visit.
    •Eligibility of tapering defined per protocol for corticosteroids, MTX/lefluomide, and tofacitinib.
    •In subjects with sJIA: “Absence of Fever”, defined as absence of fever due to sJIA in the week preceding the assessment at each visit.
    • In subjects with Enthesitis Related Arthritis (ERA): Change from baseline in the Tender Entheseal Assessment, Modified Schober's Test, Overall Back Pain and Nocturnal Back Pain response at various visits.
    • In subjects with psoriatic arthritis (PsA): Change from baseline in body surface area (BSA) affected by psoriasis and Physician's Global Assessment (PGA) of psoriasis) at various visits.
    Se evaluarán los siguientes parámetros de la eficacia:
    - Evaluación global por parte del médico de la actividad de la enfermedad en cada visita.
    - Número de articulaciones con artritis activa en cada visita.
    - Número de articulaciones con limitación del movimiento en cada visita.
    - Índice de inflamación (proteína C reactiva [PCR] y velocidad de sedimentación globular [VSG]) en cada visita.
    - Cuestionario de evaluación de la salud en la infancia (Childhood Health Assessment Questionnaire, CHAQ) en cada visita.
    - Evaluación de la función física por parte del progenitor (Índice de discapacidad de CHAQ).
    - Evaluación del dolor artrítico del niño por parte del progenitor (Índice de molestias de CHAQ, Escala visual analógica [EVA]).
    - Evaluación global del bienestar general por parte del progenitor (subsección de CHAQ, EVA).
    - Respuesta según el Colegio Estadounidense de Reumatología (American College of Rheumatology, ACR) de la AIJ y presencia de exacerbaciones de la enfermedad según ACR de AIJ en cada visita.
    - Estado clínico de enfermedad inactiva según ACR de AIJ y remisión clínica con medicación en cada visita.
    - Cambio respecto al inicio en la puntuación de actividad de la enfermedad para artritis juvenil (Juvenile Arthritis Disease Activity Score, JADAS) 27 PCR y JADAS 27 VSG, y presencia de actividad mínima de la enfermedad y enfermedad inactiva según JADAS en cada visita.
    - Elegibilidad para la retirada gradual de corticosteroides, MTX/leflunomida y tofacitinib, definida según el protocolo.
    - En pacientes con AIJ sistémica: “ausencia de fiebre”, definida como la ausencia de fiebre debida a AIJs en la semana anterior a la evaluación en cada visita.
    - En pacientes con artritis relacionada con entesitis (ARE): Cambio respecto al inicio en la evaluación de la entesitis dolorosa a la palpación, la prueba de Schober modificada, el dolor de espalda general y el dolor de espalda nocturno en varias visitas.
    - En pacientes con artritis psoriásica (APs): Cambio respecto al inicio en el área de superficie corporal (ASC) afectada por la psoriasis y la Evaluación global por parte del médico (Physician's Global Assessment, PGA) de la psoriasis en varias visitas.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The Secondary endpoints (section 2.2.2) will be assessed at Baseline, and Months 1, 3, 6, 9, and 12. During study years 2 - 10 the assessments will be completed at 6 month intervals.
    Se evaluarán en la línea de base y en los meses 1, 3, 6, 9 y 12. Durante los años de estudio 2 a 10, las evaluaciones se completarán cada 6 meses.
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    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 Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Tolerabilidad
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA18
    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
    Argentina
    Australia
    Belgium
    Brazil
    Canada
    Chile
    Germany
    Hungary
    Israel
    Italy
    Mexico
    New Zealand
    Peru
    Philippines
    Poland
    Russian Federation
    Slovakia
    South Africa
    Spain
    Switzerland
    Taiwan
    Turkey
    Ukraine
    United Kingdom
    United States
    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
    LVLS, according to the Protocol.
    última visita del último paciente según protocolo
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years10
    E.8.9.2In all countries concerned by the trial months0
    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: 340
    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) No
    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: 35
    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 Yes
    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 incapable of giving informed consent.
    Menores incapaces de dar su consentimiento informado.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 340
    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)
    Subjects may participate in extension up to 10 years. It is expected that drug will be approved when subjects’ participation ends.
    Los sujetos pueden participar en la extensión hasta 10 años. Se espera que la droga será aprobada cuando la participación de los sujetos termine.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation PRINTO
    G.4.3.4Network Country Italy
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-03-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-03-08
    P. End of Trial
    P.End of Trial StatusOngoing
    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 © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA