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    Summary
    EudraCT Number:2017-004293-33
    Sponsor's Protocol Code Number:RPC01-3202
    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:2018-03-02
    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 number2017-004293-33
    A.3Full title of the trial
    Induction Study #2 - A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Oral Ozanimod as Induction Therapy for Moderately to Severely Active Crohn’s Disease
    Estudio de inducción n.º 2: estudio de fase 3, multicéntrico, aleatorizado, con enmascaramiento doble y comparativo con placebo, en el que se evalúa ozanimod por vía oral como tratamiento de inducción para la enfermedad de Crohn activa de moderada a grave.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Multicenter Study of Oral Ozanimod as Induction Therapy in patients with Moderately to Severely Active Crohn’s Disease
    Estudio multicéntrico de ozanimod oral como tratamiento de inducción en pacientes con enfermedad de Crohn activa de moderada a grave
    A.4.1Sponsor's protocol code numberRPC01-3202
    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 SponsorCelgene International II Sàrl
    B.1.3.4CountrySwitzerland
    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 supportCelgene International II Sàrl
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationReceptos Services, LLC
    B.5.2Functional name of contact pointBarrett Levesque
    B.5.3 Address:
    B.5.3.1Street Address3033 Science Park Road, Suite 300
    B.5.3.2Town/ citySan Diego, California
    B.5.3.3Post code92121
    B.5.3.4CountryUnited States
    B.5.4Telephone number+18582917051
    B.5.6E-mailblevesque@celgene.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 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.3.1Product nameozanimod
    D.3.2Product code RPC1063 (equivalent to ozanimod HCl)
    D.3.4Pharmaceutical form Capsule, hard
    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 INNOzanimod
    D.3.9.3Other descriptive nameOZANIMOD
    D.3.9.4EV Substance CodeSUB181335
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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.3.1Product nameozanimod
    D.3.2Product code RPC1063 (equivalent to ozanimod HCl)
    D.3.4Pharmaceutical form Capsule, hard
    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 INNOzanimod
    D.3.9.3Other descriptive nameOZANIMOD
    D.3.9.4EV Substance CodeSUB181335
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Moderately to Severely Active Crohn’s Disease
    Enfermedad de Crohn activa de moderada a grave
    E.1.1.1Medical condition in easily understood language
    Crohn’s Disease
    Enfermedad de Crohn
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    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
    Demonstrate the efficacy of ozanimod compared to placebo on the induction of clinical remission
    Demostrar la eficacia de ozanimod, en comparación con el placebo, desde el punto de vista de la inducción de la remisión clínica
    E.2.2Secondary objectives of the trial
    - Demonstrate the efficacy of ozanimod compared to placebo on induction of clinical response, clinical remission, endoscopic response, endoscopic remission, and histologic improvement
    - Demonstrate the efficacy of ozanimod compared to placebo, in subjects who had previously received biologic therapy (eg, anti-IL-12, anti-IL-23, anti-TNF, or anti-integrin therapy)
    - Characterize the population pharmacokinetics (PK) and PK/pharmacodynamics (PD) relationship of ozanimod
    - Demonstrate the safety and tolerability of ozanimod as induction therapy
    - Demostrar la eficacia de ozanimod, en comparación con el placebo, desde el punto de vista de la inducción de la respuesta clínica, la remisión clínica, la respuesta endoscópica, la remisión endoscópica y la mejoría histológica.
    - Demostrar la eficacia de ozanimod, en comparación con el placebo, en los pacientes que han recibido tratamientos biológicos (por ejemplo, tratamiento anti-IL-12, anti-IL-23, anti-TNF o antintegrina).
    - Caracterizar la farmacocinética poblacional (FC) y la relación FC/farmacodinámica (FD) de ozanimod.
    - Demostrar la seguridad y la tolerabilidad de ozanimod como tratamiento de inducción.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female subjects aged 18 to 75 years (at Screening), inclusive.
    2. Subject must provide written informed consent prior to any study-related procedures, and
    have the ability to comply with the Table of Events.
    3. Subject has signs and symptoms consistent with a diagnosis of CD for at least 3 months (prior to first IP administration). The diagnosis should be confirmed by clinical and endoscopic evidence and corroborated by a histology report. (Note: endoscopy and histopathology confirmation may be obtained during Screening if no prior report is readily available).
    4. Subject has met each of the following 2 criteria:
    - a CDAI score >= 220 and =< 450
    - an average daily stool frequency >= 4 points and/or an abdominal pain of >= 2 points.
    5. Subject has a SES-CD score of >= 6 (or SES-CD >= 4 in subjects with isolated ileal disease).
    6. Subject has an inadequate response or loss of response to or is intolerant of at least 1 of the following CD treatments: corticosteroids, immunomodulators, biologic therapy (eg, ustekinumab, TNFα antagonists, or vedolizumab).
    7. If the subject is taking the following background therapies for CD, he/she must be on a stable dose as indicated below:
    - Oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) with a stable dose for at least 3 weeks prior to Screening endoscopy
    - Prednisone (doses =< 20 mg per day) or equivalent with a stable dose for at least 2 weeks prior to Screening endoscopy
    - Budesonide therapy (doses =< 9 mg per day) or beclomethasone doses =< 5 mg/day at a stable dose for at least 2 weeks prior to the Screening endoscopy.
    8. Subject at high risk (ie, family history, CD duration) for colonic malignancy has documented evidence of having had a surveillance colonoscopy within the last 2 years or according to local and national medical guidelines to evaluate for polyps, dysplasia, or malignancy. If there is no recent history of surveillance colonoscopy, this can be done as part of the colonoscopy performed during Screening. Any visualized adenomatous polyps must be removed and any suspicious lesion confirmed free of cancer and/or dysplasia prior to randomization.
    9. Female subjects of childbearing potential:
    Must agree to practice a highly effective method of contraception throughout the study until completion of the Safety Follow-Up Visit. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl Index of less than 1% per year when used consistently and correctly. Acceptable methods
    of birth control in the study are the following:
    - Combined hormonal (containing oestrogen and progestogen) contraception, which may be oral, intravaginal, or transdermal
    - Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
    - Placement of an intrauterine device (IUD)
    - Placement of an intrauterine hormone-releasing system (IUS)
    - Bilateral tubal occlusion
    - Vasectomised partner
    - Sexual abstinence
    Male subjects:
    Must agree to use a latex condom during sexual contact with women of childbearing potential while participating in the study until completion of the safety follow-up visit.
    All subjects:
    Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
    10. Subjects must have documentation of positive varicella zoster virus (VZV) immunoglobulin G (IgG) antibody status or complete VZV vaccination at least 30 days prior to randomization.
    1. Pacientes de ambos sexos y de entre 18 y 75 años de edad (ambos inclusive) en el momento de la selección.
    2. Los pacientes deben proporcionar su consentimiento informado por escrito antes de cualquier procedimiento relacionado con el estudio y deben poder cumplir los procedimientos del calendario de actividades.
    3. El paciente ha presentado signos y síntomas compatibles con un diagnóstico de EC durante al menos 3 meses (antes de la primera administración del PEI). El diagnóstico debe confirmarse por los signos clínicos y endoscópicos y corroborarse en el informe histológico. (Nota: si no se dispone de un informe previo, la confirmación endoscópica e histopatológica debe realizarse durante la selección).
    4. El paciente debe haber cumplido los dos criterios siguientes:
    - Una puntuación >= 220 y =< 450 en el índice CDAI.
    - Un promedio de la frecuencia diaria de deposiciones >= 4 puntos o dolor abdominal >= 2 puntos.
    5. El paciente presenta una puntuación >= 6 en el índice SES-CD (o >= 4 en caso de afectación ileal aislada).
    6. El paciente no tolera o presenta una respuesta insuficiente o ya no responde al menos a 1 de los tratamientos siguientes para la EC (en el anexo B se incluye información adicional):
    - Corticoesteroides
    - Inmunomoduladores
    - Tratamientos biológicos (por ejemplo, ustekinumab, antagonistas del TNFα o vedolizumab).
    7. Si el paciente recibe los siguientes tratamientos de base para la EC, debe recibir una dosis estable, según se indica a continuación:
    - Aminosalicilatos orales (por ejemplo, mesalamina, sulfasalazina, olsalazina, balsalazida) en una dosis estable al menos durante las 3 semanas anteriores a la endoscopia de la selección
    - Prednisona (dosis =< 20 mg/día) o fármaco equivalente en una dosis estable al menos durante las 2 semanas anteriores a la endoscopia de la selección.
    - Tratamiento con budesonida (dosis =< 9 mg/día) o dosis de beclometasona =< 5 mg/día en una dosis estable al menos durante las 2 semanas anteriores a la endoscopia de la selección.
    8. Los pacientes con riesgo alto de neoplasias malignas del colon (por los antecedentes familiares o la duración de la EC) deben presentar información documentada de que se han sometido a una colonoscopia de seguimiento en el transcurso de los 2 últimos años (o de conformidad con las guías médicas locales y nacionales) para evaluar la presencia de pólipos, displasia y neoplasias malignas. Si no se ha realizado una colonoscopia de seguimiento recientemente, esta puede realizarse en el marco de la colonoscopia que se realice durante la selección. Cualquier pólipo adenomatoso que se visualice debe extirparse y antes de la aleatorización debe confirmarse que cualquier lesión sospechosa no presenta cáncer ni displasia.
    9. Mujeres fértiles:
    Deben estar de acuerdo en utilizar un método anticonceptivo muy eficaz a lo largo del estudio y hasta la finalización de la visita de seguimiento de la seguridad. Por “método anticonceptivo muy eficaz” se entiende el método que, por sí mismo o combinado con otros, presenta una tasa de fallo inferior al 1 % anual (de acuerdo con el índice de Pearl), cuando se utiliza de forma sistemática y correcta. Los métodos anticonceptivos aceptables durante el estudio son los siguientes:
    - Anticonceptivos hormonales combinados (que contienen estrógeno y progesterona) orales, intravaginales o transdérmicos.
    - Anticonceptivos gestagénicos que inhiben la ovulación y que pueden ser orales, inyectables o implantables.
    - Implantación de un dispositivo intrauterino (DIU).
    - Implantación de un sistema intrauterino liberador de hormona (SIU).
    - Ligadura de trompas.
    - Vasectomía de la pareja.
    - Abstinencia sexual.
    Varones:
    Deben estar de acuerdo en utilizar preservativo de látex durante las relaciones sexuales con mujeres fértiles, mientras participen en el estudio y hasta que realicen la visita de seguimiento de seguridad.
    Todos los pacientes:
    La abstinencia periódica (métodos del calendario, sintotérmico, posovulación), la retirada (coitus interruptus), el uso solo de espermicidas y el método de la amenorrea de la lactancia no son métodos anticonceptivos aceptables. El preservativo femenino y el preservativo masculino no pueden utilizarse simultáneamente.
    10. Documentación de que el paciente presenta inmunoglobulinas G (IgG) frente al virus de la varicela zóster (VVZ) o ha sido vacunado frente al VVZ al menos 30 días antes de la aleatorización.
    E.4Principal exclusion criteria
    1. Subject has any clinically relevant hepatic, neurological, pulmonary, ophthalmological, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study
    2. Subject is likely to require, in the physician's judgment, bowel resection within 12 weeks of entry into the study
    3. Subject has a diagnosis of UC, indeterminate colitis, radiation colitis, or ischemic colitis, or has known strictures or stenosis leading to symptoms of obstruction.
    4. Subject has current stoma, ileal-anal pouch anastomosis, symptomatic fistula, or need for ileostomy or colostomy.
    5. Subject has extensive small bowel resection (> 100 cm) or known diagnosis of short bowel syndrome, or subject requires total parenteral nutrition.
    6. Subject has suspected or diagnosed intra-abdominal or perianal abscess that has not been appropriately treated.
    7. Subject has documentation of a positive test for toxin producing C. difficile, or PCR examination of the stool on their most recent test, which must have been done in the past 60 days.
    8. Subject has documentation of positive examination for pathogens (ova and parasites, and bacteria), which must have been done in the past 60 days.
    9. Subject is pregnant, lactating, or has a positive serum beta human chorionic gonadotropin (β-hCG) measured during Screening.
    10. Subject has clinically relevant cardiovascular conditions, making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study
    11. Subject has a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with HbA1c > 9%, or is a diabetic subject with significant comorbid conditions such as retinopathy or nephropathy.
    12. Subject has a history of uveitis (within last year) or clinically confirmed diagnosis of macular edema
    13. Subject has a known active bacterial, viral, fungal, mycobacterial infection, or other infection or any major episode of infection that required hospitalization or treatment with IV antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening
    14. History or known presence of recurrent or chronic infection (eg, virus HBV, HCV or HIV); recurrent urinary tract infections are allowed
    15. Subject has a history of active cancer within 5 years, including solid tumors and hematological malignancies or colonic dysplasia that has not been completely removed
    16. Subject has a history of alcohol or drug abuse within 1 year prior to initiation of Screening
    17. Subject has a history of primary nonresponse to 2 or more approved biologic therapies used for the treatment of CD
    18. Subject has been treated with a biologic agent within 8 weeks or 5 elimination half-lives prior to the first dose of IP
    19. Subject has a history of treatment with an investigational agent within 5 elimination half-lives of that agent prior to the first dose of IP 20. Subject has received a live vaccine within 4 weeks prior to the first dose of IP
    21. Subject has received previous treatment with lymphocyte-depleting therapies
    22. Subject has received previous treatment with D-penicillamine, leflunomide, or thalidomide
    23. Subject has received previous treatment with natalizumab or fingolimod
    24. Subject has received previous treatment with cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 16 weeks of initiation of Screening
    25. Subject has a history of treatment with IVIg, or plasmapheresis within 3 months prior to first dose of IP
    26. Subject has discontinued oral or rectal 5-ASA or corticosteroids within 2 weeks prior to the screening endoscopy.
    27. Subject has planned concurrent treatment with immunomodulatory agents after randomization. Subjects receiving azathioprine, 6-MP, or methotrexate at screening must discontinue treatment with these agents prior to first dose of IP
    28. Subject has chronic nonsteroidal anti-inflammatory drug (NSAID) use (note: occasional use of NSAIDs and acetaminophen [eg, headache, arthritis, myalgias, or menstrual cramps] and aspirin up to 325 mg/day is permitted)
    29. Subject treated with Class Ia or Class III anti-arrhythmic drugs or with 2 or more agents in combination known to prolong PR interval.
    30. Subject has screening ECG results showing any clinically significant abnormality.
    31. Subject has serum creatinine results >1.4 mg/dL for women or > 1.6 mg/dL for men.
    32. Subject has liver function impairment or persisting elevations of AST or ALT results > 2 times the ULN, or direct bilirubin > 1.5 times the ULN.
    33. Subject has a platelet count < 100,000/μL.
    34. Subject has hemoglobin < 7.5 g/dL
    35. Subject has neutrophils < 1500/μL
    36. Subject has an absolute WBC count <3500/μL
    37. Subject has an ALC < 800 cells/μL
    38. Subject has a FEV1 or FVC <70% of predicted values at screening
    1. El paciente presenta enfermedad hepática, neurológica, pulmonar, oftalmológica, endocrina o psiquiátrica clínicamente relevante, u otra enfermedad sistémica importante que dificulte la ejecución del protocolo o la interpretación de sus resultados o que pondría al paciente en riesgo.
    2. Es probable que requiera resección intestinal durante las 12 semanas posteriores a la inclusión en el estudio.
    3. Se le ha diagnóstico colitis ulcerosa, colitis indeterminada, colitis por radiación o colitis isquémica o presenta estrechamientos o estenosis asociados con síntomas de obstrucción
    4. Presenta estoma, reservorio ileal-anal con anastomosis, fístula sintomática o precisa ileostomía o colostomía
    5. Se ha sometido a una resección amplia (> 100 cm) del intestino delgado, se le ha diagnosticado síndrome del intestino corto o requiere nutrición parenteral total
    6. Se le ha diagnosticado o se sospecha que presenta un absceso intraabdominal o perianal no tratado
    7. Presenta resultado positivo y documentado a la prueba de C. difficile productora de toxinas o se le ha hecho exploración de muestras fecales mediante una reacción PCR en la prueba más reciente, hecha en los últimos 60 días.
    8. Presenta un resultado positivo documentado en análisis de patógenos (huevos y parásitos y bacterias), realizado en los últimos 60 días.
    9. La paciente está embarazada, en período de lactancia o ha dado resultado positivo en una prueba de embarazo en suero (β HCG) en la selección.
    10. Presenta enfermedad cardiovascular clínicamente relevante que dificultaría la ejecución del protocolo o la interpretación de sus resultados o que pondría al paciente en riesgo
    11. Antecedentes de diabetes mellitus de tipo 1 o de tipo 2 sin controlar, con una concentración de HbA1c > 9 %, o paciente diabético con enfermedades concomitantes, como retinopatía o nefropatía.
    12. Antecedentes de uveitis (en el último año) o diagnóstico de edema macular confirmado clínicamente.
    13. Presenta infección bacteriana, vírica, fúngica o micobacteriana activa u otra infección importante que haya requerido la hospitalización o tratamiento con antibióticos intravenosos durante los 30 días anteriores a la selección o con antibióticos orales durante los 14 días anteriores
    14. Antecedentes o presencia de infección recurrente o crónica (por ej. virus de hepatitis VHB, VHC o VIH )
    15. Antecedentes de neoplasia maligna activa durante los 5 últimos años, incluidos los tumores sólidos y las neoplasias hematológicas malignas, o de displasias del colon que no se hayan extirpado por completo
    16. Antecedentes de consumo excesivo de alcohol o toxicomanía durante el año anterior a la selección
    17. No ha presentado respuesta primaria a 2 o más tratamientos biológicos autorizados para el tratamiento de la EC
    18. Ha recibido un producto biológico durante las 8 semanas anteriores a la primera dosis del PEI
    19. Ha recibido tratamiento con un fármaco en investigación en el transcurso de un período anterior a la primera dosis del PEI equivalente a 5 semividas de eliminación de ese fármaco.
    20. Ha recibido una vacuna elaborada con microbios vivos durante las 4 semanas anteriores a la primera dosis del PEI.
    21. Ha recibido tratamientos que reducen el número de linfocitos
    22. Ha recibido tratamiento con D-penicilamina, leflunomida o talidomida.
    23. Ha recibido tratamiento con natalizumab o fingolimod.
    24. Ha recibido tratamiento con ciclosporina, tacrolimus, sirolimus o micofenolato de mofetilo durante las 16 semanas anteriores al inicio del período de selección.
    25. Ha recibido tratamiento i.v. con concentrados de inmunoglobulinas o se ha sometido a una plasmaféresis en los 3 meses anteriores a la primera dosis del PEI.
    26. Ha interrumpido el tratamiento con 5-ASA o corticosteroides por vía oral o rectal, durante las 2 semanas anteriores a la endoscopia que se realizará durante la selección.
    27. Tiene previsto recibir tratamiento concomitante con fármacos inmunomoduladores tras la aleatorización. Los pacientes que en el momento de la selección reciban azatioprina, 6-MP o metotrexato deben interrumpir estos tratamientos antes de la primera dosis del PEI.
    28. Toma AINEs de forma prolongada
    29. Ha recibido antiarrítmicos de clase Ia o clase III o dos o más fármacos combinados que prolongan el intervalo PR
    30. Presenta alteraciones clínicamente importantes en el ECG realizado durante la selección.
    31. La concentración sérica de creatinina es > 1,4 mg/dl (mujeres) o > 1,6 mg/dl (varones)
    32. Presenta disfunción hepática o elevaciones continuas de la concentración de AST o de ALT > 2 veces al LSN o una concentración de bilirrubina directa > 1,5 veces el LSN
    33. Presenta cifra de trombocitos < 100,000/μl
    34. Pesenta oncentración de hemoglobina < 7,5 g/dl
    35. Pesenta cifra de neutrófilos < 1500/μl
    36. Pesenta cifra WBC < 3500/μl
    37. Pesenta cifra absoluta de linfocitos (ALC) < 800 células/μl
    38. Pesenta VEMS o CVF < 70 % de los valores previstos en la selección
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of subjects with a CDAI score < 150 at Week 12
    Porcentaje de pacientes con una puntuación < 150 en el índice CDAI en la semana 12.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Subjects will be deemed a responder with respect to this endpoint if they meet the definition for CDAI Clinical Remission at Week 12.
    Se considerará que los sujetos cumplen con respecto a este criterio de valoración si cumplen con la definición de remisión clínica del CDAI en la semana 12.
    E.5.2Secondary end point(s)
    Major Secondary Endpoints:
    - Proportion of subjects with average daily abdominal pain score =< 1 point, and average daily stool frequency score =< 3 points and a stool frequency score no worse than baseline at Week 12
    - Proportion of subjects with a Simple Endoscopic Score for Crohn’s Disease (SES CD) score decrease from baseline of >= 50% at Week 12
    - Proportion of subjects with CDAI reduction from baseline of >= 100 points or CDAI score < 150 at Week 12
    - Proportion of subjects with CDAI reduction from baseline of >= 100 points or CDAI score < 150 and SES-CD decrease from baseline of >= 50% at Week 12
    Principales criterios secundarios de valoración:
    - Porcentaje de pacientes con un promedio de la puntuación diaria del dolor abdominal =< 1 punto y un promedio de la puntuación relativa a la frecuencia diaria de las deposiciones =< 3 puntos y cuya puntuación relativa a la frecuencia de las deposiciones en la semana 12 no haya empeorado respecto a la del período basal.
    - Porcentaje de pacientes que en la semana 12 presenten una reducción en la puntuación endoscópica simple para la enfermedad de Crohn (SES-CD) de >= 50 % respecto a la del período basal.
    - Porcentaje de pacientes que en la semana 12 presenten una reducción >= 100 puntos en el índice CDAI respecto a la puntuación basal o una puntuación < 150 puntos en este índice.
    - Porcentaje de pacientes que en la semana 12 presenten una reducción >= 100 puntos en el índice CDAI respecto a la puntuación basal o una puntuación < 150 puntos en este índice y una reducción en el índice SES-CD de >= 50 % respecto a la del período basal.
    E.5.2.1Timepoint(s) of evaluation of this end point
    at Week 12
    En la semana 12
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.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) No
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA109
    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
    Austria
    Bulgaria
    Canada
    China
    Finland
    France
    Georgia
    Germany
    Greece
    Hong Kong
    Hungary
    Israel
    Korea, Republic of
    Lithuania
    Mexico
    Netherlands
    Poland
    Portugal
    Russian Federation
    Saudi Arabia
    Serbia
    Singapore
    Slovakia
    Slovenia
    South Africa
    Spain
    Sweden
    Turkey
    Ukraine
    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
    The end of study is defined as either the date of the last visit of the last subject to complete the safety follow-up, or the date of receipt of the last datapoint from the last subject that is required for primary or secondary analysis, as prespecified in the protocol, whichever is the later date.
    El final del estudio se define como la fecha de la última visita del último paciente que complete el seguimiento de la seguridad o la fecha en la que se reciba el último dato del último paciente necesario para efectuar el análisis principal o secundario, de acuerdo con las especificaciones previas del protocolo (la fecha que sea posterior).
    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 years3
    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 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: 540
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 60
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 226
    F.4.2.2In the whole clinical trial 600
    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 will be entering the Maintenance Study or Open-label Extension Study. If not entering these studies they will have a Safety Follow-Up Visit (30 to 45 days after the last dose of IP).
    Los sujetos entrarán en el estudio de mantenimiento o en el estudio de extensión sin enmascaramiento. Si no entran en estos estudios, se les realizará una visita de seguimiento de seguridad (de 30 a 45 días después de la última dosis de PEI).
    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 Decision2018-04-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-03-26
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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