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    Summary
    EudraCT Number:2012-003644-71
    Sponsor's Protocol Code Number:B1801355
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2012-12-21
    Trial results View 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 number2012-003644-71
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Etanercept in Subjects with Rheumatoid Arthritis Who Have Had and Inadequate Response to Adalimumab or Infliximab Plus Methotrexate.
    ESTUDIO ALEATORIZADO, EN DOBLE CIEGO Y CONTROLADO CON PLACEBO, DE LA SEGURIDAD Y LA EFICACIA DE ETANERCEPT EN SUJETOS CON ARTRITIS REUMATOIDE QUE HAN PRESENTADO UNA RESPUESTA INADECUADA A ADALIMUMAB O INFLIXIMAB MÁS METOTREXATO
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Randomized, Double-Blind, Placebo-Controlled Trial of etanercept plus methotrexate in monoclonal antibody (mAb) anti-TNF failure
    Estudio aleatorizado, doble ciego, contralado con placebo de Etanercept más metotrexato con fallo a anticuerpos monoclonales (mAb) anti-TNF.
    A.4.1Sponsor's protocol code numberB1801355
    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 SponsorPfizer Inc.
    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 pointClinicalTrials.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+1800718 1021
    B.5.5Fax number+1303739 1119
    B.5.6E-mailClinicalTrials.gov_Inquiries@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 Enbrel
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ltd., Sandwich, Kent, UK
    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.3.1Product nameEnbrel
    D.3.4Pharmaceutical form Solution for injection in pre-filled syringe
    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.3.9.4EV Substance CodeSUB01984MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion in pre-filled syringe
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Rheumatoid Arthritis
    Artritis reumatoide
    E.1.1.1Medical condition in easily understood language
    Rheumatoid Arthritis
    Artritis reumatoide
    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 14.1
    E.1.2Level PT
    E.1.2Classification code 10039073
    E.1.2Term Rheumatoid 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
    To compare the efficacy of etanercept to placebo in inadequate responders to infliximab or adalimumab plus methotrexate (MTX) in all subjects and in subjects who are anti-drug antibody positive (ADA+) to one of these monoclonal antibodies (mAbs).
    El objetivo principal de este estudio es comparar la eficacia del etanercept y el placebo en sujetos con una respuesta inadecuada a infliximab o adalimumab más Metotrexato MTX, en todos los sujetos y en los sujetos con anticuerpos antifármaco positivos (ADA+) contra uno de estos anticuerpos monoclonales.
    E.2.2Secondary objectives of the trial
    To assess the effect of ADA status on the efficacy of etanercept in inadequate responders to infliximab or adalimumab plus MTX.
    To evaluate the safety of etanercept in inadequate responders to infliximab or adalimumab plus MTX.
    Valorar el efecto de la situación en cuanto a ADA sobre la eficacia del etanercept en sujetos con una respuesta inadecuada a infliximab o adalimumab más MTX.
    Evaluar la seguridad del etanercept en sujetos con una respuesta inadecuada a infliximab o adalimumab más MTX.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator´s study team before subjects are included in the study.
    Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
    1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
    2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
    3. Subject is literate and able to complete the protocol-specified questionnaires.

    Period 1 Inclusion Criteria
    In addition to the criteria in Section 4.1, subjects must meet all of the following inclusion criteria to be eligible for enrollment into Period 1 of the study:
    1. Male or female >= 18 years and <80 years of age at the time of consent.
    2. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 12 weeks after the last dose of assigned treatment. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active (see Section 4.5 Life Style Guidelines)..
    3. Met the 1987 ACR Revised Criteria for RA (see Appendix 1).
    4. A history of inadequate efficacy response to at least a 6-month course of either infliximab or adalimumab with at least the last 4 weeks before the screening visit receiving a combination of either infliximab plus MTX or adalimumab plus MTX.
    5. For subjects receiving infliximab, the last dose of infliximab must have been received within 6 to 8 weeks before the screening mAb ADA test.
    6. For subjects receiving adalimumab, the last dose of adalimumab must have been received within 11 to 17 day before the screening mAb ADA test.
    7. Stable dose of oral MTX (10 mg QW to 25 mg QW) for >=6 weeks before the baseline visit.
    8. Active RA at the screening visit, defined as all of the following:
    a. CRP >= 1.0 mg/L
    b. >= 6 tender joints based on the 28 joint assessment (see Section 7.1.5)
    c. >= 6 swollen joints based on the 28 joint assessment (see Section 7.1.5)
    9. Active RA at the baseline visit, defined as all of the following:
    a. >= 6 tender joints based on the 28 joint assessment (see Section 7.1.5)
    b. >= 6 swollen joints based on the 28 joint assessment (see Section 7.1.5)
    10.In the opinion of the investigator, subject is a reasonable candidate for treatment with etanercept plus MTX.
    11.Either the subject or a designee must be capable (according to the investigator?s judgment) of administering the SC investigational product and must be able to store all investigational product under required storage conditions or must be able to come to the study site for administrations where the investigational product may be stored on behalf of the subject.
    12.Active and latent TB must be ruled out by screening for TB in accordance with local country guidelines; subjects with recent exposure to active TB must be evaluated by a qualified physician to rule out TB (see Period 1 Exclusion Criteria 20).
    13.Female subjects of childbearing potential per the investigator´s opinion must have negative urine pregnancy test results based on the screening visit and baseline visit tests (see Section 7.4.1 Pregnancy Testing). This includes subjects who are menstruating at the time of the visit and/or who are not sexually active.

    Escape Arm Inclusion Criteria
    The subject must meet all of the following criteria to be included in the Escape Arm of the study:
    1. The subject has completed the week 8 visit of the study.
    2. Less than 10% improvement in either the tender/painful joint count or the swollen joint count at the week 8 visit as compared to the baseline joint counts (see Appendix 1 for examples).
    Subject must be willing to continue stable dose of all RA medications that the subject is using at Week 8 through Week 24 (except when dose adjustment is allowed according to Section 5.5 Concomitant Medications).

    Period 2 Inclusion Criteria
    The subject must meet all of the following criteria to be included in Period 2 of the study:
    1. Subject has completed Period 1 (ie, the week 12 visit) of the study.
    2. Subject must be willing to continue stable dose of all RA medications that the subject is using at Week 12 through Week 24 (except when dose adjustment is allowed according to Section 5.5 Concomitant Medications).
    Un miembro adecuadamente cualificado del equipo del estudio del investigador examinará y documentará la elegibilidad del sujeto antes de su inclusión en el estudio.
    Los sujetos deben cumplir todos los criterios de inclusión siguientes para ser elegibles a entrar en el estudio:
    1. Prueba de un documento de consentimiento informado, firmado y fechado personalmente, que indique que el sujeto (o su representante legal) ha sido informado de todos los aspectos pertinentes del estudio.
    2. Sujetos que estén dispuestos y sean capaces de cumplir las visitas programadas, el plan de tratamiento, los análisis de laboratorio y otros procedimientos del estudio.
    3. El sujeto sabe leer y escribir, y es capaz de cumplimentar los cuestionarios especificados en el protocolo.

    Criterios de inclusión en el periodo 1
    Además de los criterios señalados en la sección 4.1, los sujetos deben cumplir todos los criterios de inclusión siguientes para ser elegibles a entrar en el periodo 1 del estudio:
    1. Varón o mujer >= 18 años y < 80 años de edad en el momento del consentimiento.
    2. Los sujetos de ambos sexos potencialmente fértiles deben comprometerse a utilizar un método anticonceptivo de gran eficacia a lo largo del estudio y durante como mínimo 12 semanas después de la última dosis del tratamiento asignado.
    3. Cumplir los criterios revisados del ACR para artritis reumatoide.
    4. Antecedentes de respuesta inadecuada en cuanto a eficacia al menos a un ciclo de 12 semanas de infliximab o adalimumab, de las que como mínimo, las últimas 4 semanas de administración del anticuerpo monoclonal correspondiente hayan sido en combinación con MTX.
    5. En el caso de los sujetos tratados con infliximab, deben haber recibido la última dosis de infliximab en el plazo de las 6 a 8 semanas anteriores a la prueba de mAb ADA de la selección.
    6. En el caso de los sujetos tratados con adalimumab, deben haber recibido la última dosis de adalimumab en el plazo de los 11 a 17 días anteriores a la prueba de mAb ADA de la selección.
    7. Dosis estable de MTX oral (de 10 mg una vez a la semana a 25 mg una vez a la semana) durante >= 6 semanas antes de la visita basal.
    8. AR activa en la visita de selección, definida por todos los criterios siguientes:
    a. Proteína C-reactiva >=1,0 mg/L.
    b. >= 6 articulaciones con dolor a la palpación según la evaluación de 28 articulaciones.
    c. >= 6 articulaciones con tumefacción según la evaluación de 28 articulaciones.
    9. AR activa en la visita basal, definida por todos los criterios siguientes:
    a.>= 6 articulaciones con dolor a la palpación según la evaluación de 28 articulaciones.
    b. >= 6 articulaciones con tumefacción según la evaluación de 28 articulaciones.
    10. En opinión del investigador, el sujeto es un candidato razonable al tratamiento con etanercept más MTX.
    11. El sujeto o una persona designada deben ser capaces de administrar el producto en investigación por vía subcutánea y poder almacenar todo el producto en investigación en las condiciones de conservación exigidas, o bien ser capaces de acudir para las administraciones al centro del estudio, donde se podrá conservar el producto en investigación para el sujeto.
    12. Deberá haberse descartado una tuberculosis activa o latente mediante cribado de TB en conformidad con las directrices locales del país; un médico cualificado deberá evaluar a los sujetos que hayan tenido una exposición reciente a TB activa para descartar esta enfermedad.
    13. Las mujeres potencialmente fértiles en opinión del investigador deben presentar resultados negativos en las pruebas de embarazo en orina realizadas en las visitas de selección y basal. Se incluye aquí a las sujetos que estén menstruando en el momento de la visita y/o que no sean sexualmente activas.
    Criterios de inclusión en el grupo de rescate
    El sujeto debe cumplir todos los criterios siguientes para entrar en el grupo de rescate del estudio:
    1. El sujeto ha completado la visita de la semana 8 del estudio.
    2. Resultado peor que una mejoría del 10% en el número de articulaciones con dolor a la palpación/espontáneo o en el número de articulaciones con tumefacción en la visita de la semana 8 en comparación con los recuentos articulares basales.
    3. El sujeto está dispuesto a continuar con una dosis estable de todos los medicamentos para la AR que estuviera recibiendo en la semana 8 hasta la semana 24 (excepto cuando se permita un ajuste de la dosis según lo señalado en la sección 5.5 Medicamentos concomitantes).
    Criterios de inclusión en el periodo 2
    1. El sujeto ha completado el periodo 1 (es decir, la visita de la semana 12) del estudio.
    2. El sujeto está dispuesto a continuar con una dosis estable de todos los medicamentos para la AR que estuviera recibiendo en la semana 12 hasta la semana 24 (excepto cuando se permita un ajuste de la dosis según lo señalado en la sección 5.5 Medicamentos concomitantes).
    E.4Principal exclusion criteria
    Period 1 Excl. Criteria
    1.Investigational site staff members or relatives of those site staff members or Pfizer employees directly involved in trial conduct.
    2.ACR functional class IV.
    3.Prior treatment with etanercept, any immunosuppressive biologic agent other than infliximab or adalimumab, or both infliximab and adalimumab.
    4.Discontinuation of infliximab or adalimumab for a primary reason other than inadequate efficacy response.
    5.For subjects receiving infliximab, a dose >10 mg/kg every 4 weeks within 12 weeks before baseline.
    6.For subjects receiving adalimumab, a dose >40 mg every other week within 12 weeks before baseline.
    7.Subject has a known or suspected allergy, hypersensitivity, or contraindication to MTX or its components or to etanercept, its excipients, or other compounds related to this class of medication, including biopharmaceutical proteins.
    8.> 1 permitted non-biologic DMARD other than MTX or change in dose or regimen of the additional permitted non-biologic DMARD within 4 weeks before baseline.
    9.Cyclophosphamide, cyclosporine, or azathioprine within 6 months before baseline.
    10.Leflunomide without elimination procedure within 8 weeks before baseline or within 4 weeks of baseline if the protocol-specified elimination procedure is followed.
    11.Any investigational non-biologic drugs or devices within 12 weeks before baseline and/or during study B1801355.
    12.Non-biologic DMARDs other than those permitted during the study or which are not listed under other exclusion criteria within 8 weeks before baseline.
    13.>10 mg/day of oral prednisone (or equivalent),or change in dose within 2 weeks before baseline.
    14.IA or soft tissue corticosteroid injection or bolus IM or IV corticosteroids within 4 weeks before baseline.
    15.> 1 NSAID or change in dose or type of NSAID within 2 weeks before baseline.
    16.Any live (attenuated)vaccines within 4 weeks before baseline.
    17.Any of the following hematology or chemistry laboratory abnormalities based on screening test results.
    a.WBC count<=3.5 x 109/L;
    b.Hemoglobin level <=85 g/L or <=5.3mmol/L;
    c.Hematocrit <=27%;
    d.Platelet count <=125 x 109/L;
    e.Serum creatinine level >=175 µmol/L or >=1.98 mg/dL;
    f.AST or ALT level ?2 times upper limit of normal.
    18.Any other clinically significant laboratory results or vital sign measurements.
    19.Active TB, or evidence of untreated latent or active TB.
    20.Any infection associated with hospitalization and/or parenteral anti-infective agents within 4 weeks before baseline.
    21.Active infection at screening and/or baseline, including systemic fungal infections.
    22.Any clinically relevant concurrent medical conditions, including:
    a.Uncompensated congestive heart failure, Class III or IV heart failure, or any episode of acute congestive heart failure within 6 months before screening;
    b.Uncontrolled hypertension;
    c.Myocardial infarction within 12 months before screening;
    d.Coronary artery bypass graft or percutaneous transluminal coronary angioplasty within 12 months before screening;
    e.Unstable angina pectoris within 6 months before screening;
    f.Presence or history of severe pulmonary disease requiring recurrent hospitalizations or supplemental oxygen;
    g.Presence or history of confirmed blood dyscrasias;
    h.Diagnosis of multiple sclerosis or other central or peripheral nervous system demyelinating diseases;
    i.Malignancy or history of malignancy (except non metastatic basal cell or squamous cell skin carcinoma; or cervical carcinoma in situ);
    j.Uncontrolled diabetes mellitus;
    k.Diagnosis of systemic lupus erythematosus, scleroderma, or polymyositis;
    l.Open cutaneous ulcers;
    m.History of clinically significant drug induced liver injury, cirrhosis or fibrosis;
    n.Known history, or presence of, hepatitis C or chronic hepatitis B infection; or positive test result at screening for hepatitis C virus or chronic hepatitis B;
    o.Known history, presence of, or positive test result history for HIV.
    23.Other severe acute or chronic medical or psychiatric condition or lab abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with interpretation of study results and, in the investigator´s judgment, would make the subject inappropriate for entry into this study.
    24.Any anticipated or planned surgical procedure during the study period.
    25.Pregnant or breastfeeding females.
    26.Sexually active males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 12 weeks after last dose of investigational product.
    Escape Arm Excl. Criteria
    1.Discontinuation of investigational product for any reason prior to completion of the week 8 visit or for a primary reason other than inadequate efficacy response.
    Period 2 Excl. Criteria
    1.Discontinuation of investigational product for any reason prior to completion of the week 12 visit.
    Exclusión periodo 1
    1.Sujetos o familiares miembros del personal del centro, o sujetos empleados de Pfizer involucrados directamente en la realización del ensayo.
    2. Clase funcional IV del ACR.
    3. Tratamiento previo con Etanercept,o con producto biológico inmunodepresor distinto de infliximab o adalimumab, o ambos Infliximab y adalimumab.
    4.Suspensión de administración de infliximab o adalimumab por una razón distinta de respuesta inadecuada en cuanto a eficacia.
    5.Sujetos que reciban infliximab, dosis >10 mg/kg cada 4 semanas en las 12 semanas anteriores a la v. basal.
    6. Sujetos que reciban adalimumab, dosis >40 mg en semanas alternas, en las 12 semanas anteriores a la v. basal.
    7. Sujeto con diagnóstico de certeza o de sospecha de alergia, hipersensibilidad o contraindicación al MTX o sus componentes, al etanercept, sus excipientes u otros compuestos relacionados con esta clase de medicación, incluidas las proteínas biofarmacéuticas.
    8. >1 FARME no biológico permitido distinto de MTX, o cambio de dosis o de pauta del FARME no biológico permitido adicional en las 4 semanas anteriores a v. basal.
    9. Ciclofosfamida, ciclosporina o azatioprina en los 6 meses anteriores a v. basal.
    10.Leflunomida sin procedimiento de eliminación en las 8 semanas anteriores a v. basal o, si se ha seguido el procedimiento de eliminación, en las 4 semanas anteriores a v. basal.
    11. Fármaco o producto sanitario no biológico en investigación en las 12 semanas anteriores a v. basal y/o durante el estudio B1801355.
    12. FARME no biológicos distintos de los permitidos durante el estudio o que no figuren en otros criterios de exclusión en las 8 semanas anteriores a v. basal.
    13. > 10 mg/día de prednisona oral (o equivalente) o cambio de la dosis en las 2 semanas anteriores a v. basal.
    14. 1 i.a. o en tejidos blandos de corticosteroides, o tratamiento en bolo i.m. o i.v. con corticosteroides en el plazo de las 4 semanas anteriores a v. basal.
    15. >1 AINE o cambio de la dosis o el tipo de AINE en las 2 semanas anteriores a v. basal.
    16. Cualquier vacuna atenuada en las 4 semanas anteriores a v. basal.
    17.Cualquiera de las siguientes alteraciones analíticas en los resultados de las pruebas de selección:
    Recuento leucocitario <= 3,5 × 109/L;
    Concentración de hemoglobina <= 85 g/L o <= 5,3 mmol/L;
    Hematocrito <= 27%;
    Plaquetas <=125 × 109/L;
    Creatinina sérica >= 175 µmol/L o >= 1,98 mg/dL;
    AST o ALT >= 2 veces LSN.
    18.Otro resultado analítico o determinación de las constantes vitales clínicamente importante.
    19.TB activa o pruebas de TB activa o latente no tratada.
    20.Infección asociada a una hospitalización y/o administración parenteral de productos antinfecciosos en las 4 semanas anteriores a v. basal.
    21.Infección activa en la v. de selección y/o basal, incluidas las fúngicas sistémicas.
    22.Cualquier proceso médico, incluidos:
    a. Insuficiencia cardiaca congestiva descompensada, de clase III o IV. o cualquier episodio de insuficiencia cardiaca congestiva aguda en los 6 meses anteriores a v. de selección;
    b.Hipertensión no controlada
    c.Infarto de miocardio en los 12 meses anteriores a v. de selección;
    d.Derivación coronaria o angioplastia coronaria transluminal percutánea en los 12 meses anteriores a v. de selección;
    e.Angina de pecho inestable en los 6 meses anteriores a v. de selección;
    f.Presencia o antecedentes de neumopatía severa.
    g.Presencia o antecedentes de discrasias sanguíneas confirmadas;
    h.Diagnóstico de esclerosis múltiple u otras enfermedades desmielinizantes.
    i.Antacedentes de/o Neoplasia maligna.
    j.Diabetes mellitus no controlada;
    k.Diagnóstico de LES, esclerodermia o polimiositis;
    l.Úlceras cutáneas abiertas;
    m.Antecedentes de lesión hepática inducida por fármacos, cirrosis o fibrosis;
    n.Antecedentes o presencia de infección por el VHC o infección crónica por el VHB; o resultado positivo en la selección por VHC o VHB crónica.
    o.Antecedentes o presencia de o resultado positivo de VIH.
    23.Otros casos que pudieran aumentar el riesgo asociado a la participación en el estudio.o a la administración del producto en investigación, o que pudieran alterar la interpretación de los resultados del estudio y, a juicio del investigador, hicieran que el sujeto no fuera adecuado para entrar en este estudio
    24.Intervención quirúrgica prevista o programada durante el estudio.
    25.Mujeres embarazadas o en lactancia.
    26.Varones y mujeres potencialmente fértiles y sexualmente activos que no utilicen un método anticonceptivo de gran eficacia o no utilizado de manera continua durante 12 semanas después de la última dosis.
    Criterios de excl. del grupo de rescate
    1. Suspensión del producto en investigación antes de completar la v. de la semana 8 o por razón distinta de la respuesta inadecuada en cuanto a eficacia.
    Criterios de exclusión del periodo 2
    1. Suspensión del producto en investigación antes de completar la v. de la semana 12.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in the disease activity score based on a 28 joint count (DAS28-CRP) at week 12
    The primary study comparison is between etanercept 50 mg QW and placebo in all subjects, as determined by the change from baseline in DAS28-CRP scores at week 12.
    The conditional primary study comparison is between etanercept 50 mg QW and placebo in subjects who are mAb ADA+, as determined by the change from baseline in DAS28-CRP scores at week 12.
    Cambio respecto al momento basal en la puntuación de la actividad de la enfermedad según el recuento de 28 articulaciones (con la proteína C-reactiva: DAS28-CRP) en la semana 12.
    La comparación principal del estudio se realizará entre 50 mg de etanercept una vez a la semana y placebo en todos los sujetos, determinada por el cambio respecto al momento basal en las puntuaciones de DAS28-CRP en la semana 12.
    La comparación principal condicional del estudio se realizará entre 50 mg de etanercept una vez a la semana y placebo en los sujetos mAb ADA+, evaluada mediante el cambio respecto al momento basal en las puntuaciones de DAS28-CRP en la semana 12.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks
    12 semanas
    E.5.2Secondary end point(s)
    Key Secondary Efficacy Endpoint
    Change from baseline in the DAS28-CRP at week 24
    The key secondary study comparison will be between subjects who are mAb ADA+ and mAb ADA- and are randomized to etanercept, as determined by the change from baseline in DAS28-CRP scores at week 24.

    Additional Secondary Efficacy Endpoints
    The following endpoints will be assessed at all timepoints unless otherwise noted:
    ? Change from baseline in DAS28-CRP
    ? DAS28-CRP < 3.2 and DAS28-CRP < 2.6
    ? American College of Rheumatology (ACR) 20, ACR50, ACR70, and ACR90
    ? European League Against Rheumatism (EULAR) good response and EULAR good/moderate response
    ? Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI)
    ? Individual components of the ACR and DAS
    ? Vectra disease activity (DA) levels (at baseline, week 4, week 12, and week 24, or upon early withdrawal)
    Cambio respecto al momento basal en DAS28 CRP en la semana 24.
    La comparación secundaria clave del estudio se realizará entre los sujetos que sean mAb ADA+ y mAb ADA- y hayan sido aleatorizados al etanercept, de acuerdo con el cambio respecto al basal en las puntuaciones de DAS28-CRP en la semana 24.
    E.5.2.1Timepoint(s) of evaluation of this end point
    24 weeks
    24 Semanas
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    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.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 Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    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 concerned4
    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 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
    Australia
    Chile
    Colombia
    Czech Republic
    France
    Germany
    Hong Kong
    Israel
    Netherlands
    Russian Federation
    Spain
    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
    End of Trial in all participating countries is defined as the Last Subject Last Visit.
    Se define como fin del ensayo en todos los países participantes la última visita del último sujeto.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days15
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 140
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 28
    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 No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state26
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 78
    F.4.2.2In the whole clinical trial 168
    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)
    No administration of Enbrel is planned after the subject has ended the participation in the trial. Subject is expected to receive 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 Decision2013-03-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-02-28
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    The status of studies in GB is no longer updated from 1.1.2021
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