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    Summary
    EudraCT Number:2017-004209-41
    Sponsor's Protocol Code Number:CNTO1275CRD3007
    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:2018-05-21
    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 number2017-004209-41
    A.3Full title of the trial
    A Phase 3b, Multicenter, Randomized, Blinded, Active-Controlled Study to Compare the Efficacy and Safety of Ustekinumab to that of Adalimumab in the Treatment of Biologic Naïve Subjects with Moderately-to-Severely Active Crohn’s Disease
    Estudio de fase IIIb, multicéntrico, aleatorizado, ciego y controlado con tratamiento activo para comparar la eficacia y la seguridad de ustekinumab frente adalimumab en el tratamiento de pacientes con enfermedad de Crohn con actividad de moderada a grave previamente no tratados con fármacos biológicos
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Compare the Efficacy and Safety of Ustekinumab With Adalimumab in the Treatment of Subjects With Moderately-to-Severely Active Crohn’s Disease, not Undergone Treatment With Biologic
    Estudio para comparar la eficacia de Ustekinumab con Adalimumab en el tratamiento de pacientes con enfermedad de Crohn con actividad de moderada a grave, previamente no tratados con biológicos.
    A.3.2Name or abbreviated title of the trial where available
    SEAVUE: Safety and Efficacy of Adalimumab Versus Ustekinumab for one yEar
    SEAVUE: Seguridad y Eficacia de Adalimumab Versus Ustekinumab por un año
    A.4.1Sponsor's protocol code numberCNTO1275CRD3007
    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 SponsorJanssen-Cilag International N.V.
    B.1.3.4CountryBelgium
    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 supportJanssen Research & Development, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag. S.A.
    B.5.2Functional name of contact pointGlobal Clinical Operations Spain
    B.5.3 Address:
    B.5.3.1Street AddressPaseo de las Doce Estrellas, 5-7
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28042
    B.5.3.4CountrySpain
    B.5.4Telephone number34917228100
    B.5.5Fax number34917228628
    B.5.6E-mailagonza45@its.jnj.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 STELARA®
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    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 nameUstekinumab
    D.3.2Product code CNTO1275
    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 INNUstekinumab
    D.3.9.1CAS number 815610-63-0
    D.3.9.2Current sponsor codeCNTO1275
    D.3.9.4EV Substance CodeSUB27761
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number90
    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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal Antibody
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name STELARA®
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    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 nameUstekinumab
    D.3.2Product code CNTO1275
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNUstekinumab
    D.3.9.1CAS number 815610-63-0
    D.3.9.2Current sponsor codeCNTO1275
    D.3.9.4EV Substance CodeSUB27761
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal Antibody
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Humira®
    D.2.1.1.2Name of the Marketing Authorisation holderAbbvie Ltd.
    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 nameAdalimumab
    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 INNADALIMUMAB
    D.3.9.1CAS number 331731-18-1
    D.3.9.4EV Substance CodeSUB20016
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Yes
    D.3.11.13.1Other medicinal product typeMonoclonal Antibody
    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 injection
    D.8.4Route of administration of the placeboIntravenous use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection 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
    Crohn’s Disease
    Enfermedad de Crohn
    E.1.1.1Medical condition in easily understood language
    A chronic inflammatory bowel disease that affects the lining of the digestive tract.
    Enfermedad inflamatoria crónica intestinal que afecta el revestimiento del tracto digestivo
    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 10011401
    E.1.2Term Crohn's disease
    E.1.2System Organ Class 10017947 - Gastrointestinal 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 treatment with ustekinumab or adalimumab in biologic naïve subjects with moderately-to-severely active Crohn's disease (CD) who have previously failed or were intolerant to conventional therapy (corticosteroids and/or immunomodulators, ie, azathioprine [AZA], 6 mercaptopurine [6-MP], or methotrexate [MTX]), as measured by clinical remission at one year.
    Comparar la eficacia del tratamiento con ustekinumab frente a adalimumab, determinada a partir de la remisión clínica después de un año, en pacientes con EC (enfermedad de Crohn) con actividad de moderada a grave, previamente no tratados con fármacos biológicos y con fracaso o intolerancia a los tratamientos convencionales (corticoesteroides y/o inmunomoduladores, es decir, azatioprina, 6-mercaptopurina, o metotrexato)
    E.2.2Secondary objectives of the trial
    To evaluate the following in biologic naïve subjects with moderately-to-severely active CD treated with ustekinumab or adalimumab:
    • Other measures of clinical efficacy (eg, clinical response) including reductions in frequent concomitant medications associated with adverse outcomes (eg steroids, narcotics)
    • Anti-inflammatory efficacy assessed with biomarkers (eg, fecal calprotectin, C-reactive protein)
    • Endoscopic endpoints (eg, endoscopic remission)
    • Safety (eg, proportions of subjects with serious adverse events, all adverse events, etc.)
    • CD-related healthcare utilization (eg, CD-related hospitalizations, surgeries, emergency room [ER] visits) and the need to initiate another biologic treatment
    • Patient-reported outcome (PRO) assessments, such as Inflammatory Bowel Disease Questionnaire (IBDQ) and Patient Reported Outcome Measurement Information System (PROMIS).
    Evaluar los siguientes puntos en pacientes con EC con actividad de moderada a grave, previamente no tratados con fármacos biológicos y en tratamiento con ustekinumab o adalimumab:
    • Otras medidas de eficacia clínica (p. ej., respuesta clínica), incluidas las reducciones de los medicamentos concomitantes habituales que se asocian con resultados adversos (p. ej., corticoides, narcóticos)
    • Eficacia antinflamatoria, evaluada mediante biomarcadores (p. ej., calprotectina fecal, proteína C-reactiva)
    • Criterios de valoración endoscópicos (p. ej., remisión endoscópica)
    • Seguridad (p. ej., proporciones de pacientes con acontecimientos adversos graves, todos los acontecimientos adversos, etc.)
    • Utilización de atención sanitaria en relación con la EC (p. ej., hospitalizaciones, intervenciones quirúrgicas, visitas al SU [servicio de urgencias]) relacionadas con la EC, y necesidad de iniciar otro tratamiento con fármacos biológicos
    • Evaluaciones de los PROs, como el IBDQ y el PROMIS.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    A subject must meet the following criteria to be enrolled:
    1. Be male or female (according to their reproductive organs and functions assigned by chromosomal complement) ≥18 years of age
    2. Has CD or fistulizing CD of at least 3 months duration, with colitis, ileitis, or ileocolitis, confirmed at some time in the past by radiography, histology, and/or endoscopy
    3. Has moderately-to-severely active CD with a baseline Crohn’s disease activity index (CDAI) score of ≥ 220 and ≤ 450
    4. Has one or more ulceration on screening ileocolonoscopy which will result in an Simple Endoscopic Score for Crohn’s Disease (SES-CD) total score of at least 3
    Note: If a subject had an ileocolonoscopy but then screen failed for another reason, if he/she is rescreened within 3 months, then that ileocolonoscopy is sufficient for inclusion if all other entry criteria are met
    5. Meets the following requirements for prior or current medications for CD:
    a) Has failed conventional therapy:
    i) Is currently receiving corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP) at adequate therapeutic doses; OR
    ii) Has a history of failure to respond to, or tolerate, an adequate course of corticosteroids and/or immunomodulators (ie, AZA, MTX, or 6-MP); OR
    iii) Is corticosteroid dependent or has a history of corticosteroid dependency;
    AND b) Has not previously received an approved biologic for CD (ie, infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab, vedolizumab or approved biosimilars of these agents)
    6. Subjects on oral corticosteroids (eg, prednisone, budesonide) at a prednisone-equivalent dose of ≤ 40 milligram (mg)/day or ≤ 9 mg/day of budesonide are permitted provided doses meeting these requirements are stable for 3 weeks prior to baseline (Week 0) or these have been discontinued at least 3 weeks prior to baseline
    7. Subjects on the immunomodulators AZA, 6-MP, or MTX at screening (or recently prior), must discontinue these medications at least 3 weeks prior to baseline
    8. Has screening laboratory test results within the following parameters:
    a) Hemoglobin: ≥ 8.5 gram per decilitre (g/dL)
    b) White blood cells (WBC): > 3.5 x 103/microlitre (µL)
    c) Neutrophils: >1.5 x 103/µL
    d) Platelets: > 100 x 103/µL
    e) Serum creatinine: < 1.7 milligram per decilitre (mg/dL)
    f) Aspartate transaminase (AST) and alanine transaminase (ALT) concentrations:
    Within 2 times the upper limit of normal range for the laboratory conducting the test
    g) Direct (conjugated) bilirubin: < 1.0 mg/dL
    9. Is considered eligible per the following tuberculosis (TB) screening criteria:
    a) Has no history of latent or active TB prior to screening; exceptions are made for a subject who:
    • Is currently receiving treatment for latent TB without evidence of active TB (or has initiated treatment for latent TB prior to Week 0 study agent administration)
    • Has a history of latent TB and documentation of having completed adequate treatment for latent TB within 5 years prior to the first administration of study agent.
    It is the responsibility of the investigator to verify the adequacy of previous TB treatment and provide/obtain appropriate documentation.
    b) Has no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
    c) Has had no recent, known close contact with a person with active TB or, if there has been such contact, the subject is to be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to, or simultaneously with, the first administration of study agent.
    d) Within 2 months prior to the first administration of study agent, either has:
    • A negative QuantiFERON-TB Gold test, or
    • A newly identified positive QuantiFERON-TB Gold test in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to, or simultaneously with, the first administration of study agent.
    A subject whose first QuantiFERON-TB Gold test result is indeterminate should have the test repeated. In the event that additional QuantiFERON-TB Gold test result is persistently indeterminate, the subject should also initiate treatment for latent TB in order to enter the study.
    The QuantiFERON-TB Gold In-Tube test is not required at screening for subjects with a history of latent TB and appropriate treatment as described above.
    e) Has a chest radiograph (at least a posterior-anterior view), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB

    For a complete overview please refer to the Protocol
    Criterios de inclusión:
    1. Ser varón o hembra (de acuerdo con sus órganos reproductivos y
    funciones asignadas en los cromosomas) ≥18 años.
    2. Tener EC o EC fistulizante de al menos 3 meses de duración, con colitis,
    ileítis o ileocolitis, confirmada en algún momento en el pasado por una radiografía, histología, y/o endoscopia.
    3. Tener EC con actividad de moderada a grave con puntaje en el momento basal en el índice de la EC (CDAI) de ≥ 220 y ≤ 450
    4. Tener una o más úlceras en la ileocolonoscopia del periodo de selección que resultarán en un puntaje de al menos 3 en SES-CD.

    Nota: si un paciente tuvo una ileocolonoscopia pero luego tuvo un fallo en el proceso de selección, si dentro de 3 meses se presenta de nuevo al proceso de selección, la ileocolonoscopia es suficiente para la inclusión si todos los otros criterios de selección se cumplen.
    5. Cumple con los siguientes requisitos para medicamentos previos o actuales para EC:
    a) Ha fallado la terapia convencional:
    i) Está recibiendo actualmente corticosteroides y/o inmunomoduladores (es decir, AZA, MTX o 6-MP) a dosis terapéuticas adecuadas; O
    ii) Tiene antecedentes de falta de respuesta o tolerancia a un curso adecuado de corticosteroides y / o inmunomoduladores (es decir, AZA, MTX o 6-MP);
    O
    iii) Es dependiente de corticosteroides o tiene antecedentes de dependencia;
    Y b) No ha recibido previamente un biológico aprobado para EC (es decir,
    infliximab, adalimumab, certolizumab pegol, ustekinumab, natalizumab,
    vedolizumab o biosimilares aprobados de estos fármacos)
    6. Pacientes con corticosteroides orales (p. ej., prednisona, budesónida) en
    dosis equivalentes a prednisona de ≤ 40 miligramos (mg) / día o budesónida de ≤ 9 mg / día, están permitidos siempre que las dosis cumplan con estos requisitos durante 3 semanas antes del momento basal (Semana 0) o hayan sido descontinuado al menos 3 semanas antes del momento basal.
    7. Pacientes con inmunomoduladores AZA, 6-MP o MTX en el proceso de selección (o recientemente anterior), deben descontinuar estos medicamentos por lo menos 3 semanas antes del momento de basal
    8. Tener resultados de pruebas de laboratorio en el proceso de selección dentro de los siguientes parámetros:
    a) Hemoglobina: ≥ 8,5 gramos por decilitro (g / dL)
    b) Glóbulos blancos (WBC):> 3,5 x 103 / microlitro (μL)
    c) Neutrófilos:> 1.5 x 103 / μL
    d) Plaquetas:> 100 x 103 / μL
    e) Creatinina sérica: <1.7 miligramos por decilitro (mg / dL)
    f) Concentraciones de AST y ALT: Dentro de 2 veces el límite superior del rango normal para el laboratorio conduciendo la prueba
    g) Bilirrubina directa (conjugada): <1.0 mg / dL
    9. Se considera elegible según los siguientes criterios de tuberculosis (TB):
    a) No tiene antecedentes de TB latente o activa antes del proceso de selección; excepciones para pacientes que:
    • Actualmente reciben tratamiento para TB latente sin evidencia de
    TB activa (o ha iniciado el tratamiento para la TB latente antes de la semana 0 administración del fármaco)
    • Tiene un historial de tuberculosis latente y documentación de haber completado tratamiento para la TB latente dentro de los 5 años antes a la primera administración del fármaco del estudio.
    Es responsabilidad del investigador verificar la idoneidad del
    tratamiento previo de TB y proporcionar/obtener documentación apropiada.
    b) No tiene signos o síntomas que sugieran la presencia de TB activa en la historia médica y/o examen físico.
    c) No ha tenido contacto cercano reciente conocido con una persona con TB activa o, si ha habido tal contacto, el paciente debe ser referido a un
    médico especializado en TB para someterse a una evaluación adicional y, si
    garantizado, recibir el tratamiento apropiado para la TB latente antes de, o
    simultáneamente con, la primera administración del fármaco del estudio.
    d) Dentro de los 2 meses anteriores a la primera administración del fármaco del estudio, tiene ya sea:
    • Una prueba de QuantiFERON-TB Gold negativa, o
    • Una prueba de QuantiFERON-TB Gold positiva en la que la TB activa se
    ha descartado y para la cual el tratamiento apropiado para la TB latente ha iniciado antes o al mismo tiempo que la primera administración del fármaco del estudio.
    Un paciente cuyo primer resultado de la prueba de QuantiFERON-TB Gold es indeterminado debería repetir la prueba. En caso de que el resultado de la prueba es persistentemente indeterminado, el paciente también debe iniciar el tratamiento de la TB latente para ingresar al estudio.
    La prueba QuantiFERON-TB Gold In-Tube no es necesaria en la detección de pacientes con antecedentes de TB latente y tratamiento apropiado como descrito arriba.
    e) Tiene una radiografía de tórax (al menos una toma posterior-anterior), tomada dentro de los 3 meses antes de la primera administración del fármaco del estudio y examinada por un radiólogo calificado, sin evidencia de tuberculosis actual, activa o antigua, TB inactiva
    Para obtener una descripción completa, consulte el Protocolo
    E.4Principal exclusion criteria
    A subject who meets any of the following criteria may not be enrolled in the study:
    1. Has complications of CD that are likely to require surgery or would confound the ability to assess the effect of ustekinumab or adalimumab treatment using the CDAI, such as: Short-gut syndrome and severe or symptomatic strictures or stenosis
    2. Currently has, or is suspected to have, an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior for intra-abdominal abscesses, if there is no anticipated need for any further surgery. Subjects with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses present
    3. Has had any kind of bowel resection within 6 months prior to baseline or other intra-abdominal surgery or a hospital admission for bowel obstruction within 3 months prior to baseline
    4. At any time received any monoclonal antibody (including biosimilars) targeting tumor necrosis factor alfa (TNFα), IL-12, or IL-23, or anti-integrin agents approved for CD (ie, vedolizumab or natalizumab) or has received any of the following medications or therapies within the specified periods prior to baseline:
    a) Any other investigational agent for CD (eg other biologics, small molecules or anti-sense ribonucleic acid (RNA) such as mongersen), unless at least 3 months or 5 half-lives have elapsed since last dose
    b) Intravenous (IV) corticosteroids as a treatment for CD < 3 weeks prior to baseline
    c) Oral immunomodulatory agents other than AZA, 6-MP, or MTX (eg, Janus kinase [JAK] inhibitors, 6-thioguanine [6-TG], cyclosporine, tacrolimus, sirolimus, tofacitinib, or mycophenolate mofetil) < 4 weeks prior to baseline
    (Note that per inclusion criterion 7, typical immunomodulator agents [AZA, 6-MP or MTX] must have been discontinued at least 3 weeks prior to baseline.)
    d) Treatment with apheresis (eg, Adacolumn apheresis) or total parenteral nutrition (TPN) as a treatment for CD < 3 weeks prior to baseline
    5. Has a stool culture or other examination positive for an enteric pathogen, including Clostridium difficile toxin, in the last 4 months unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen
    6. Has received a Bacillus Calmette–Guérin (BCG) vaccination within 12 months or any other live bacterial or live viral vaccination within 2 weeks of baseline
    7. Has a history of, or ongoing, chronic or recurrent infectious disease, including but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection (eg, recurrent pyelonephritis or chronic nonremitting cystitis), or infected skin wounds or ulcers
    8. Has current signs or symptoms of infection, or recent (within 8 weeks prior to baseline) history of herpes zoster or serious infection (including any requiring hospitalization)
    Established nonserious infections (eg, acute upper respiratory tract infection, simple urinary tract infection) need not be considered exclusionary at the discretion of the investigator
    9. Has evidence of current active infection, including TB, or a nodule suspicious for lung malignancy on screening or any other available chest radiograph, unless definitively resolved surgically or by additional imaging and with source document confirmation
    10. Has a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening. Refer to inclusion criteria for information regarding eligibility with a history of latent TB
    11. Has ever had a nontuberculous mycobacterial infection or serious opportunistic infection (eg, cytomegalovirus causing colitis, Pneumocystis jiroveci, aspergillosis)
    12. Is seropositive for antibodies to hepatitis C (HCV) without a history of clearance or successful treatment, defined as being negative for HCV RNA in the past year and, if treated, at least 24 weeks after completing antiviral treatment
    13. Tests positive for HBV surface antigen (HBsAg), regardless of the results of other hepatitis B tests. Subjects who test positive only for core antibody (anti-HBc) must undergo further testing for hepatitis B DNA acid (HBV DNA test). If the HBV DNA test is positive, the subject is not eligible for this study. If the HBV DNA test is negative, the subject is eligible for this study. In the event the HBV DNA test cannot be performed, the subject is not eligible for the study
    14. Is infected with human immunodeficiency virus (HIV; positive serology for HIV antibody)
    15. Has a concomitant diagnosis or any history of congestive heart failure or demyelinating disease
    16. Has current signs or symptoms, or a history of severe, progressive, or uncontrolled renal, hepatic, hematologic, endocrine, pulmonary, cardiac, neurologic, systemic lupus erythematosus, or psychiatric diseases

    For a complete overview please refer to the Protocol
    Criterios de Exclusión:
    1. Tener complicaciones de la EC que probablemente requieran cirugía o alterarían la capacidad de evaluar el efecto de ustekinumab o adlimumab utilizando el índice CDAI, como: síndrome del intestino corto y estenosis o estenosis severas o sintomáticas 2. Actualmente tiene, o se sospecha que tiene, un absceso. Abscesos cutáneos y perianales recientes no son excluyentes si se drenan y son tratados adecuadamente al menos 3 semanas antes del momento basal, o 8 semanas antes para abscesos intraabdominales, si no hay una necesidad prevista de cirugía. Los sujetos con fístulas activas pueden incluirse si no hay una necesidad prevista cirugía y no hay abscesos presentes 3. Ha tenido algún tipo de resección intestinal dentro de los 6 meses anteriores al momento basal u otra cirugía intraabdominal o una hospitalización por obstrucción intestinal dentro de los 3 meses anteriores al momento basal. 4. Ha recibido cualquier anticuerpo monoclonal (incluidos biosimilares) dirigidos a la TNFα, IL-12 o IL-23 o fármacos antintegrina aprobados para EC vedolizumab o natalizumab) o recibido cualquiera de los siguientes medicamentos o terapias dentro de los periodos especificados antes del momento basal: a) Otro fármaco de investigación para EC (p.ej., otros biológicos, moléculas pequeñas o AR antisentido como mongersen), a menos que hayan transcurrido al menos 3 meses o 5 vidas medias desde la última dosis b) Intravenosas de corticosteroides como tratamiento para la EC <3 semanas antes del momento basal c) inmunomoduladores orales distintos de AZA, 6-MP o MTX (p. ej., JAK, 6-TG, ciclosporina, tacrolimus, sirolimus, tofacitinib o micofenolato mofetil) <4 semanas antes del momento basal (por criterio de inclusión 7, inmunomoduladores típicos [AZA, 6-MP o MTX] deben haberse suspendido al menos 3 semanas antes del momento basal.) d) Tratamiento con aféresis (p. ej., aféresis de Adacolumn) o NPT como tratamiento para la EC <3 semanas antes al momento basal. 5. Tiene cultivo de heces u otro examen positivo para un patógeno intestinal, incluida la toxina Clostridium difficile, en los últimos 4 meses a menos que un examen repetido sea negativo y no haya signos de infección en curso con ese patógeno 6. Ha recibido una vacuna de BCG dentro de 12 meses o cualquier otra vacuna viva bacteriana o vírica viva dentro de 2 semanas de referencia 7. Tiene antecedentes de enfermedad infecciosa recurrente o crónica, incluidas pero no limitadas a Infección renal crónica, infección crónica de tórax, infección recurrente del tracto urinario (p.ej., pielonefritis recurrente o cistitis crónica no remisora) o heridas o úlceras cutáneas infectadas 8. Tiene signos o síntomas de infección, o reciente (8 semanas antes del momento basal) historial de herpes zóster o infección grave (incluye cualquiera que requiera hospitalización) Infecciones no graves establecidas (p.ej., infecciones vías respiratorias superiores agudas, infección simple del tracto urinario) no necesitan ser consideradas exclusivamente a discreción del investigador 9. Evidencia de infección activa actual, incluida TB, o un nódulo sospechoso de malignidad pulmonar en el proceso de selección o en cualquier radiografía de tórax, a menos que se resuelva quirúrgicamente o por estudios adicionales y con confirmación documentada. 10. Tiene un historial de infección granulomatosa latente o activa, que incluye histoplasmosis o coccidioidomicosis, antes del momento basal. Referirse a criterios de inclusión para información respecto a la elegibilidad con un historial de TB latente. 11. Alguna vez ha tenido una infección micobacteriana no tuberculosa o infección oportunista grave (p. ej., citomegalovirus que causa colitis, Pneumocystis jiroveci, aspergillosis) 12. Es seropositivo para los anticuerpos contra el VHC sin una historia de aclaramiento o tratamiento exitoso, definido como negativo para el VHC ARN en el último año y, si se trató, al menos 24 semanas después de completar tratamiento antiviral 13. Pruebas positivas para el AgHBs, independientemente de los resultados de otras pruebas de hepatitis B. Pacientes que dan positivo para el antígeno central (anti-HBc) deben someterse a más pruebas de ADN del VHB. Si la prueba de ADN del VHB es positiva, el paciente no es elegible para este estudio. Si la prueba de ADN del VHB es negativa, el paciente es elegible para este estudio. En el caso de que la prueba de ADN del VHB no pueda ser realizada, el sujeto no es elegible para el estudio 14. Está infectado con el VIH (serología positiva para anticuerpos del VIH) 15. Tiene un diagnóstico concomitante o cualquier historia de insuficiencia cardiaca congestiva o enfermedad desmielinizante 16. Tiene signos o síntomas actuales, o una historia de enfermedades severas, progresivas, o no contraladas de renal, hepático, hematológico, endocrino, pulmonar, cardiaco, neurológico, lupus sistémico eritematoso o psiquiátrico. Para obtener una descripción completa, consulte el Protocolo
    E.5 End points
    E.5.1Primary end point(s)
    The proportion of subjects with clinical remission (defined as a Crohn’s Disease Activity Index [CDAI] score < 150) at Week 52
    La proporción de sujetos con remisión clínica (definida como enfermedad de Crohn Índice de actividad de la enfermedad [CDAI] puntaje <150 ) en la semana 52
    E.5.1.1Timepoint(s) of evaluation of this end point
    At Week 52
    En la semana 52
    E.5.2Secondary end point(s)
    1. Corticosteroid-free remission at Week 52 (defined as a CDAI score < 150 and not taking any corticosteroids for at least 30 days prior to Week 52)
    2. Clinical response (defined as a CDAI score decrease ≥100 from baseline) at Week 52
    3. Endoscopic remission (defined as an SES-CD score ≤3) at Week 52
    4. Clinical remission (defined as CDAI < 150) at Week 16
    5. The proportion of subjects with at least one adverse event (AE), and subcategories of AEs including infections, serious adverse events (SAEs), and serious infections
    6. The proportion of subjects with anti-drug antibodies
    7. The proportion of subjects who are on concomitant narcotic pain medications for CD
    8. The proportion of subjects able to eliminate concomitant narcotic pain medication use for CD
    9. The proportion of subjects who are on concomitant narcotic pain medications for any reason
    10. The proportion of subjects able to eliminate concomitant narcotic pain medication use for any reason
    11. The total number of days subjects are off narcotic pain medications through Week 52 among subjects who are on narcotic pain medication at baseline
    1. Remisión sin corticoesteroides en la semana 52 (definida por una puntuación CDAI <150 y no haber tomado corticoesteroides durante por lo menos 30 días antes de la semana 52)
    2. Respuesta clínica (definida por una disminución de la puntuación CDAI ≥100 desde el inicio) en la semana 52
    3. Remisión endoscópica (definida por una puntuación SES-CD ≤3) en la semana 52
    4. Remisión clínica (definida por un CDAI <150) en la semana 16
    5. La proporción de pacientes con al menos un evento adverso (AE) y
    subcategorías de AEs incluyendo infecciones, eventos adversos graves (EAG), e infecciones serias
    6. La proporción de pacientes con anticuerpos antidrogas
    7. La proporción de pacientes con medicamentos narcóticos para el dolor para EC
    8. La proporción de pacientes capaces de eliminar medicamentos narcóticos para el dolor concomitantes para la EC
    9. La proporción de pacientes que están con medicamentos narcóticos para el dolor concomitantes por cualquier razón
    10. La proporción de sujetos capaces de eliminar los narcóticos concomitantes
    uso de medicamentos para el dolor por cualquier razón
    11. La cantidad total de días que los pacientes están sin medicamentos narcóticos para el dolor hasta la Semana 52 entre los pacientes que toman medicamentos narcóticos para el dolor en el momento basal
    E.5.2.1Timepoint(s) of evaluation of this end point
    1, 2 & 3. At Week 52
    4. At Week 16
    5 to 11. Through Week 52
    1, 2 y 3. En la semana 52
    4. En la semana 16
    5 a 11. Hasta la semana 52
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy 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
    Immunogenicity Analyses and Biomarker assessments
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    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 Yes
    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) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    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
    Belgium
    Brazil
    Bulgaria
    Canada
    Czech Republic
    France
    Germany
    Hungary
    Italy
    Korea, Republic of
    Netherlands
    Poland
    Russian Federation
    Serbia
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    Última visita del último paciente
    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 months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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: 333
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 17
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 180
    F.4.2.2In the whole clinical trial 350
    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)
    Standard care of therapy
    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 Decision2018-06-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-06-20
    P. End of Trial
    P.End of Trial StatusOngoing
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