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    Summary
    EudraCT Number:2017-002108-28
    Sponsor's Protocol Code Number:B7581002
    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:2018-04-20
    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 number2017-002108-28
    A.3Full title of the trial
    A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFICACY, SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-06687234 AS ADD-ON THERAPY TO INFLIXIMAB IN ACTIVE ULCERATIVE COLITIS SUBJECTS WHO ARE NOT IN REMISSION (BUILD UC)
    Estudio en fase IIA, aleatorizado, con doble enmascaramiento y controlado con placebo, para evaluar la eficacia, la seguridad, la tolerabilidad y la farmacocinética de PF 06687234 como tratamiento adyuvante a infliximab en sujetos con colitis ulcerosa activa que no se encuentra en remisión (BUILD UC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the efficacy, safety, tolerability and pharmacokinetics of PF-06687234/placebo as add-on therapy to infliximab in subjects with ulcerative colitis who are not in remission
    Estudio para evaluar la eficacia, la seguridad, la tolerabilidad y la farmacocinética de PF 06687234/placebo como tratamiento complementario a infliximab en pacientes con colitis ulcerosa que no se encuentran en remisión
    A.3.2Name or abbreviated title of the trial where available
    BUILD UC
    A.4.1Sponsor's protocol code numberB7581002
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03269695
    A.5.4Other Identifiers
    Name:IND NumberNumber:122507
    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, 235 East 42nd Street, New York, New York 10017
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportPfizer Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc.
    B.5.2Functional name of contact pointClinical Trials.gov Call Center
    B.5.3 Address:
    B.5.3.1Street Address235 East 42nd Street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10017
    B.5.3.4CountryUnited States
    B.5.4Telephone number+3491 490 99 00
    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 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 nameDekavil
    D.3.2Product code PF-06687234
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDekavil
    D.3.9.2Current sponsor codePF-06687234
    D.3.9.3Other descriptive nameF8IL10
    D.3.9.4EV Substance CodeSUB177242
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 typehuman monoclonal antibody-cytokine fusion protein F8IL10
    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 placeboPowder for solution for injection
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Ulcerative colitis
    Colitis ulcerosa
    E.1.1.1Medical condition in easily understood language
    Ulcerative colitis
    Colitis ulcerosa
    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 20.1
    E.1.2Level LLT
    E.1.2Classification code 10045365
    E.1.2Term Ulcerative colitis
    E.1.2System Organ Class 100000004856
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To evaluate the efficacy of PF-06687234 in induction of clinical remission in subjects with UC and a partial response to anti-TNF-α;
    • To evaluate the safety and tolerability of PF-06687234 in subjects with UC and a partial response to anti-TNF-α.
    •Evaluar la eficacia de PF-06687234 en la inducción de la remisión clínica en pacientes con CU y una respuesta parcial a anti-TNF-α.
    •Evaluar la seguridad y la tolerabilidad de PF-06687234 en pacientes con CU y una respuesta parcial a anti-TNF-α.
    E.2.2Secondary objectives of the trial
    • To evaluate the efficacy of PF-06687234 in induction of endoscopic improvement in subjects with UC and partial response to anti-TNF-α;
    • To evaluate histological improvement in subjects with UC and partial response to anti-TNF-α;
    • To evaluate the efficacy of PF-06687234 in induction of clinical response in subjects with UC and a partial response to anti-TNF-α.
    • To describe the PK of PF-06687234 in subjects with UC.
    • To evaluate the immunogenicity of PF-06687234 in subjects with UC.
    •Evaluar la eficacia de PF-06687234 en la inducción de la mejora endoscópica en pacientes con CU y una respuesta parcial a anti-TNF-α.
    •Evaluar la mejora histológica en pacientes con CU y una respuesta parcial a anti-TNF-α.
    •Evaluar la eficacia de PF-06687234 en la inducción de la respuesta clínica en pacientes con CU y una respuesta parcial a anti-TNF-α.
    •Describir la FC de PF-06687234 en pacientes con CU.
    •Evaluar la inmunogenia de PF-06687234 en pacientes con CU.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    “Pharmacokinetic substudy” with primary objective to assess pK of administered IP
    “Subestudio farmacocinético” con el objetivo principal de evaluar la FC del PEI administrado
    E.3Principal inclusion criteria
    1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
    2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
    3. Male and/or female subjects ≥18 years to ≤75 years of age and
    weight > 40 kg at the time of informed consent.
    4. A diagnosis of active UC (histologic) for ≥4 months. A biopsy report supporting the diagnosis prior to the baseline visit must be available in the source documents. In addition, a report documenting disease duration and extent of disease (eg, proctosigmoiditis, left-sided colitis, or pancolitis) based upon prior endoscopy must also be available in the source documentation.
    5. Subjects with active UC as defined by (via screening endoscopy) a total Mayo Score ≥5 but ≤8 and an endoscopic subscore ≥2. Endoscopy (flexible sigmoidoscopy or colonoscopy), should be performed within 14 days of baseline (Day 1). The endoscopic Mayo subscore assessed by the Central Reader must be available at the baseline visit. The assessment by the Central Reader will be used to derive the total Mayo score to determine study eligibility.
    6. UC extending at least 25 cm proximal to the anal verge at the time of the screening endoscopy. Only a portion, of the 25 cm of involved colon must be graded with Mayo endoscopic subscore of 2.
    7. Must be on a stable dose 5-10 mg/kg of Remicade®, Inflectra™ or Remsima® for a minimum of 14 weeks (4 doses) and a maximum of two years prior to study entry with no anticipation of need for change in infliximab treatment regimen throughout the study (no switches from pre-study infliximab version to a different infliximab version will be permitted).
    8. Subjects currently receiving the following treatment for UC are eligible provided they have been on stable doses as described below:
    - Oral 5-aminosalicylic acid derivative (5-ASA) or sulfasalazine stable dose for at least 4 weeks prior to baseline. If oral 5-ASA treatment has been recently discontinued, it must have been stopped for at least 2 weeks prior to date of total Mayo Score assessment.
    - Oral corticosteroids (prednisone equivalent up to 20 mg/day; budesonide up to 9 mg/day) stable dose for at least 2 weeks prior to baseline. If oral corticosteroids have been recently discontinued, they must have been stopped at least 2 weeks prior to date of total Mayo Score assessment. Decreases in steroid use due to AEs are allowed.
    - 6-MP, azathioprine (AZA) (≤ 2.5 mg/kg), or MTX stable dose for 8 weeks prior to baseline.
    9. Male subjects able to father children and female subjects of childbearing potential and at risk for pregnancy must agree to use two methods of contraception throughout the study and until the Week 16 visit (or 28 days after the last dose of IP).
    - Women of childbearing potential (WOCBP) will be eligible provided these women use two methods of contraception throughout the study and until the Week 16 visit (or 28 days after the last dose of IP), as outlined in Protocol Section 4.4.
    - Female subjects of nonchildbearing potential must meet at least 1 of the following criteria:
    Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed with a serum follicle-stimulating hormone (FSH) level confirming the postmenopausal state;
    - Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    - Have medically confirmed ovarian failure.
    All other female subjects (including female subjects with tubal ligations) are considered to be of childbearing potential.
    1.Constancia de un documento de consentimiento informado firmado y fechado personalmente que indique que se ha informado al paciente de todos los aspectos pertinentes del estudio.
    2.Voluntad y capacidad de cumplir las visitas programadas, el plan de tratamiento, los análisis de laboratorio y otros procedimientos del estudio.
    3.Pacientes de sexo masculino y/o femenino de entre 18 y 75 años de edad, inclusive, y peso superior a 40 Kg en el momento del consentimiento informado.
    4.Un diagnóstico de CU (histológica) activa desde hace ≥4 meses. En los documentos originales debe haber disponible un informe de biopsia que respalde el diagnóstico antes de la visita inicial. Además, también debe estar disponible en la documentación original un informe basado en una endoscopia previa que documente la duración y la extensión de la enfermedad (p. ej., proctosigmoiditis, colitis izquierda o pancolitis).
    5.Pacientes con CU activa (en la endoscopia de selección) definida por una puntuación de Mayo total ≥5, pero ≤8, y una subpuntuación endoscópica ≥2. La endoscopia (sigmoidoscopia flexible o colonoscopia) debe realizarse dentro de los 14 días anteriores al inicio (Día 1). La subpuntuación endoscópica Mayo evaluada por el lector central debe estar disponible en la visita inicial. La evaluación del lector central se utilizará para obtener la puntuación del índice de Mayo total que determinará la idoneidad para participar en el estudio.
    6.CU que se extiende al menos 25 cm en sentido proximal al borde anal en el momento de la endoscopia de selección. Solo una porción de los 25 cm de colon afectados debe tener una subpuntuación endoscópica Mayo de 2.
    7.Debe estar en tratamiento con una dosis estable de entre 5 y 10 mg/kg de Remicade®, Inflectra™ o Remsima® durante un mínimo de 14 semanas (4 dosis) y un máximo de dos años antes de ingresar en el estudio sin previsión de necesidad de cambio del régimen de tratamiento con infliximab durante todo el estudio (no se permitirá cambiar la versión de infliximab previa al estudio por una versión diferente).
    8.Los pacientes que en la actualidad reciben los siguientes tratamientos para la CU son aptos para participar en el estudio siempre que hayan estado recibiendo dosis estables como las descritas a continuación:
    -Dosis estable de derivado del ácido 5-aminosalicílico (5-ASA) o sulfasalazina por vía oral durante, al menos, 4 semanas antes del inicio. Si el tratamiento por vía oral con 5 ASA se ha interrumpido recientemente, debe haberse detenido durante, al menos, 2 semanas antes de la fecha de la evaluación para medir la puntuación del índice de Mayo total.
    -Dosis estable de corticosteroides por vía oral (equivalente a prednisona hasta 20 mg/día; budesonida hasta 9 mg/día) durante al menos 2 semanas antes del inicio. Si los corticosteroides por vía oral se han interrumpido recientemente, deben haberse detenido durante, al menos, 2 semanas antes de la fecha de la evaluación para medir la puntuación del índice de Mayo total. Se permiten los descensos en el uso de corticosteroides debidos a AA.
    -6-MP, azatioprina (AZA) (≤2,5 mg/kg) o dosis estable de MTX durante 8 semanas antes del inicio.
    9.Los pacientes de sexo masculino que puedan tener hijos y las pacientes de sexo femenino con capacidad para concebir y en riesgo de embarazo deben acceder a utilizar dos métodos anticonceptivos durante todo el estudio y hasta la visita de la semana 16 (o 28 días después de la administración de la última dosis del PEI).
    -Las mujeres con capacidad para concebir (WOCBP) serán aptas siempre que usen dos métodos anticonceptivos durante todo el estudio y hasta la visita de la semana 16 (o 28 días después de la última dosis del PEI), como se describe en la sección 4.4 del protocolo.
    -Las mujeres sin capacidad para concebir deben cumplir al menos 1 de los siguientes criterios:
    Han alcanzado el estado posmenopáusico, definido como: cese de la menstruación periódica durante al menos 12 meses seguidos sin una causa patológica ni fisiológica alternativa; el estado posmenopáusico puede confirmarse con un nivel de hormona foliculoestimulante (FSH) sérica que lo confirme.
    -Se han sometido a una histerectomía o a una ooforectomía bilateral documentadas.
    -Han recibido confirmación médica de insuficiencia ovárica.
    Se considera que todas las demás pacientes (incluidas las pacientes con ligadura de trompas) tienen capacidad para concebir.
    E.4Principal exclusion criteria
    1. Pregnant female subjects; breastfeeding female subjects; fertile male subjects and female subjects of childbearing potential who are unwilling or unable to use 2 methods of contraception as per protocol for the duration of the study (Wk16 visit) or for at least 28 days after the last dose of IP 2. Subjects with a diagnosis or documented history of total colectomy and/or pouchitis, indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, and diverticular disease associated with colitis, or clinical findings suggestive of Crohn’s disease 3. Subjects considered in imminent need for surgery or with major elective surgery scheduled to occur during the study 4. Subjects with extensive colitis for at least 8 yrs who have not had a colonoscopy with surveillance biopsies within 2 yrs of the first screening visit 5. Subjects with history of or at screening endoscopy, biopsy documented colonic dysplasia or neoplasia 6. Subjects who require infliximab dosing interval other than every 8 wks during this study 7. Subjects displaying clinical signs of fulminant colitis or toxic megacolon 8. Subjects with primary sclerosing cholangitis 9. Subjects with known colonic stricture, or history of colonic or small bowel obstruction or resection 10. Subjects with history of or current colonic or small bowel stoma 11. History of known cyclic neutropenia, thrombocytopenia, lymphopenia, leukopenia or any history of chronic anemia (HGB <10 g/dL) which is judged by the investigator to have an unclear specific etiology or is non self-limiting 12. Abnormal findings on the chest x-ray film performed routinely before initiating a new biologic therapy, such as presence of tuberculosis (TB), general infections, heart failure, or malignancy. Chest x-ray examination may be performed up to 12 wks prior to screening. Documentation of the official reading must be located and available in the source documentation 13. Any history of either latent or active TB infection, current treatment for active or latent TB infection or evidence of currently active TB by chest x-ray, residing with or frequent close contact with individual(s) with active TB. Subjects who have a positive Mantoux (PPD) tuberculin skin test or a positive Interferon Gamma Release Assay during screening or within 12 wks prior to randomization. The following are acceptable assays: QFT-G, QFT-GIT and T-SPOT® - TB test during screening or within 12 wks prior to screening. 14. Presence of active enteric infections (positive stool culture and sensitivity). The presence of Clostridium difficile infection or pseudomembranous colitis or history of recurrent Clostridium difficile infection. Known active invasive fungal infections such as histoplasmosis or parasitic infections. 15. Known history of HIV based on documented history with positive serological test, or positive HIV serologic test at screening, tested at the site’s local lab and as per local regulations 16. Presence of transplanted organ; skin grafts are allowed 17. Previous severe hypersensitivity reaction to infliximab or known hypersensitivity to inactive components of infliximab or to any murine protein.18. Exposure to a live (attenuated) vaccine within 30days prior to screening or anticipated need for any live (attenuated) vaccine during the study 19. Significant concurrent medical condition at the time of baseline visit 20. Subjects receiving the therapies described in Protocol Sec. 4.2 within the designated time period or are expected to receive any of these therapies during the study period 21. Subjects with significant trauma or major surgery within 4 wks of screening 22. Prior evidence of liver injury or toxicity due to methotrexate 23. History of sensitivity to heparin or heparin-induced thrombocytopenia 24. Abnormality in hematology and/or chemistry profiles during screening 25. Donation of blood in excess of 500 mL within 8 wks prior to baseline 26. History of alcohol or drug abuse with less than 6 months of abstinence prior to baseline .
    Please see the Protocol Section 4.2 for the full list of exclusion criteria
    1.Pacientes de sexo femenino embarazadas; pacientes de sexo femenino en periodo de lactancia; pacientes de sexo masculino y femenino con capacidad para concebir que no desean o no pueden usar 2 métodos anticonceptivos por protocolo durante todo el estudio (visita de la semana 16) o durante al menos 28 días después de la última dosis del PEI.
    2.Pacientes con un diagnóstico o antecedentes documentados de colectomía total y/o reservoritis, colitis indeterminada, colitis microscópica, colitis isquémica, colitis infecciosa, colitis por radiación y enfermedad diverticular asociada con la colitis, o hallazgos clínicos que sugieren la enfermedad de Crohn.
    3.Pacientes considerados en inminente necesidad de cirugía o con cirugía electiva mayor programada que tenga lugar durante el estudio.
    4.Pacientes con colitis extensa durante al menos 8 años que no se han sometido a una colonoscopia con biopsias de control dentro de los 2 años anteriores a la 1ª visita de selección.
    5.Pacientes con antecedentes de displasia o neoplasia de colon documentadas mediante biopsia o bien en la endoscopia de selección.
    6.Pacientes que requieren un intervalo entre dosis de infliximab diferente de cada 8 semanas durante este estudio.
    7.Pacientes que muestran signos clínicos de colitis fulminante o megacolon tóxico.
    8.Pacientes con colangitis esclerosante primaria.
    9.Pacientes con estenosis del colon conocida o antecedentes de obstrucción o resección de colon o de intestino delgado.
    10.Pacientes con estoma de colon o de intestino delgado actual o antecedentes del mismo.
    11.Antecedentes de neutropenia cíclica, trombocitopenia, linfopenia, leucopenia o de cualquier anemia crónica (HGB <10 g/dl) conocidas que el investigador considere que tiene una etiología específica poco clara o no es autolimitante.
    12.Hallazgos anómalos en la radiografía torácica realizada de manera rutinaria antes de iniciar un nuevo tratamiento biológico, tales como la presencia de tuberculosis (TB), infecciones generales, insuficiencia cardíaca o neoplasia maligna. La exploración radiológica torácica puede realizarse hasta 12 semanas antes de la selección. La documentación de la lectura oficial debe estar ubicada y disponible en la documentación original.
    13.Cualquier antecedente de infección por TB activa o latente, tratamiento actual para infección por TB activa o latente o indicios de TB activa presente en radiografía torácica, residir o tener contacto próximo frecuente con individuos con TB activa. Pacientes que tengan una prueba cutánea de la tuberculina (PPD) de Mantoux positiva o un ensayo de liberación de interferón gamma positivo durante la selección o en las 12 semanas previas a la aleatorización. Los que siguen son análisis aceptables: QFT-G, QFT-GIT y prueba T-SPOT® - TB durante la selección o en las 12 semanas antes de la selección.
    14.Presencia de infecciones entéricas activas (cultivo de heces positivo y sensibilidad). Presencia de una infección por Clostridium difficile o colitis pseudomembranosa o antecedentes de infección recurrente por C. difficile. Micosis invasivas activas conocidas, como histoplasmosis o parasitosis.
    15.Antecedentes conocidos de VIH según los antecedentes documentados mediante una prueba serológica positiva o un resultado positivo para la prueba serológica de VIH en la selección, analizada en el laboratorio local del centro y de acuerdo con la normativa local.
    16.Existencia de un órgano trasplantado; se permiten los injertos de piel.
    17.Reacción grave de hipersensibilidad previa a infliximab o hipersensibilidad conocida a componentes inactivos de infliximab o a alguna proteína murina.
    18.Exposición a una vacuna viva (atenuada) dentro de los 30 días anteriores a la selección o necesidad prevista de alguna vacuna viva (atenuada) durante el estudio.
    19.Afección médica simultánea significativa en el momento de la visita inicial.
    20.Pacientes que reciben los tratamientos descritos en la sección 4.2 del protocolo dentro del periodo de tiempo designado o que se espera que reciban alguno de estos tratamientos durante el periodo del estudio.
    21.Pacientes con traumatismo significativo o cirugía mayor en las 4 semanas previas a la selección.
    22.Indicios previos de lesión o toxicidad hepática debido a metotrexato.
    23.Antecedentes de sensibilidad a la heparina o trombocitopenia inducida por heparina.
    24.Anomalía en los perfiles hematológicos y/o bioquímicos durante la selección.
    25.Donación de sangre de más de 500 ml en las 8 semanas previas al inicio.
    26.Antecedentes de alcoholismo o drogadicción con menos de 6 meses de abstinencia antes del inicio.
    Por favor refiéranse a la sección 4.2 del protocolo para la lista completa de criterios de exclusion.
    E.5 End points
    E.5.1Primary end point(s)
    • Proportion of subjects in clinical remission at Week 12 (as defined by a modified Mayo Score with an endoscopic subscore ≤1, stool frequency subscore ≤1 and rectal bleeding subscore = 0).
    • Incidence and severity of adverse events, serious adverse events and withdrawals due to adverse events, ECGs, vital signs and safety laboratory tests.
    •Proporción de pacientes en remisión clínica en la semana 12 (según la definición de una puntuación de Mayo modificada con una subpuntuación endoscópica ≤1, subpuntuación de frecuencia de deposiciones ≤1 y subpuntuación de rectorragia = 0).
    •Incidencia e intensidad de acontecimientos adversos, acontecimientos adversos graves y retiradas del estudio debidas a acontecimientos adversos, ECG, constantes vitales y analíticas de seguridad.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint will be analyzed at Week 12 using exact Chan and Zhang method. The difference between treatment groups in the proportion of subjects in remission at Week 12 will be presented along with its 95% confidence interval. Subjects with missing remission data at Week 12 will be treated as treatment failure. As sensitivity analyses, the primary endpoint will also be analyzed using other methods for handling missing data which will be described in the SAP.
    All clinical AEs, SAEs, TEAEs, withdrawal due to AEs, ECGs (on weeks 6,12,16), vital signs and safety laboratory data (on weeks 1,2,4,6,8,10,12,16) will be reviewed and summarized on an ongoing basis in a blinded manner during the study to evaluate the safety of subjects.
    El criterio de valoración principal se analizará en la semana 12 usando el método exacto de Chan y Zhang. La dif. entre grupos de tratamiento en la proporción de pacientes en remisión en semana 12 se presentará junto con su intervalo de confianza del 95%.Los pacientes con datos de remisión faltantes en semana 12 se tratarán como fracaso terapéutico.Como análisis de sensibilidad,también se analizará el criterio de valoración principal utilizando otros métodos para manejar datos faltantes que se describirán en el SAP. Todos los AA,AAG,AAST,retiradas por AA,ECG (semana 6,12 y 16),constantes vitales y datos de laboratorio de seguridad (semana 1,2,4,6,8,10,12 y 16) se revisarán y resumirán de manera enmascarada durante el estudio de forma continua para evaluar la seguridad de los pacientes.
    E.5.2Secondary end point(s)
    • Proportion of subjects with endoscopic improvement at Week 12 (defined as decrease of ≥1 point in Mayo endoscopy score or an absolute endoscopy score of ≤1).
    • Mean change from baseline at Week 12 in Geboes histology score.
    • Proportion of subjects with a clinical response at Week 12 defined with a decrease from baseline of at least 3 points in total Mayo score with at least 30% change, accompanied by at least one point decrease or absolute score of 0 or 1 in rectal bleeding subscore.
    • Proportion of subjects with change from baseline in partial Mayo Score of ≤2 with no individual subscore >1 at Weeks 2, 4, 6, 8, 12.
    • Plasma concentrations of PF-06687234.
    • Incidence of the development of HAFAs and Nabs against PF-06687234.
    •Proporción de pacientes con mejora endoscópica en la semana 12 (definida como un descenso de ≥1 punto en la puntuación endoscópica de Mayo o una puntuación endoscópica absoluta de ≤1).
    •Cambio medio respecto al inicio en la puntuación histológica de Geboes en la semana 12.
    •Proporción de pacientes con una respuesta clínica en la semana 12, definida por una disminución desde el inicio en la puntuación de Mayo total de al menos 3 puntos con al menos un 30 % de cambio, acompañada de al menos una disminución de un punto o una puntuación absoluta de 0 o 1 en la subpuntuación de rectorragia.
    •Proporción de pacientes con cambio desde el inicio en la puntuación de Mayo parcial ≤2 sin ninguna subpuntuación individual >1 en las semanas 2, 4, 6, 8 y 12.
    •Concentraciones plasmáticas de PF-06687234.
    •Incidencia del desarrollo de AHAF y AcN contra PF-06687234.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Subjects proportion:
    - of achieving endoscopic improvements/clinical response – as for primary endpoint;
    - with partial Mayo Score - generalized linear mixed effect model with treatment group, visit, treatment group by visit interaction and subjects as random effect.
    Change from baseline in Geboes histology score - analysis of covariance model with treatment group and baseline scores.
    PK concentration population: as all enrolled subjects who received at least one IP dose and in whom at least one concentration value is reported.
    Immunogenicity assessment population: as all enrolled subjects who received at least one IP dose with at least one post-treatment HAFA determination
    Proporción de pacientes:-que logran mejoras endoscópicas/resp. clínica como para crit. de valoración princ.-con índice de Mayo parcial, modelo lineal generalizado de efectos mixtos con grupo de tratamiento(“tto”), visita,interacción entre grupo de tto y visita y pacientes como efecto aleatorio.Cambios desde el inicio en índice histológico de Geboes,modelo lineal generalizado de efectos mixtos con grupo de tto,visita,interacción entre grupo de tto y visita y pacientes como efecto aleatorio.Población de concentración de FC:todos los pacientes que hayan recibido al menos 1 dosis de PEI y se ha documentado al menos 1 valor de concentración.Población de evaluación de inmunogenia:todos los pacientes que hayan recibido al menos 1 dosis de PEI y que hay al menos 1 determinación de AHAF tras el tto
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    tolerability, histological improvement, immunogenicity
    tolerabilidad, mejora histológica, inmunogenicidad.
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA16
    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
    Germany
    Israel
    Italy
    Korea, Republic of
    Saudi Arabia
    Serbia
    Spain
    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
    End of trial in EU is defined as the time at which it is deemed that a sufficient number of subjects have been recruited and completed the study as stated in the regulatory and ethics applications in the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a Member State is not a reason for premature termination but is considered a normal conclusion to the study in that Member State.
    End of trial in all other participating countries is defined as LSLV.
    El fin del ensayo en la UE se define como el momento en el que se considera que se han reclutado un nº suficiente de pacientes y han finalizado el estudio según las solicitudes presentadas a las agencias reguladoras y el CE en el Estado miembro(EM).Un bajo reclutamiento de pacientes(˂al número previsto en la SEC)en un EM no es motivo de finalización prematura y se considera una conclusión normal del estudio en dicho EM.El fin del ensayo en el resto de países participantes se define como la UVUP.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months2
    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: 88
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 98
    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)
    When the trial completes the patients will revert to the local standard of care for Ulcerative Colitis.
    Cuando concluya el ensayo, los pacientes volverán al tratamiento estándar local para la colitis ulcerosa.
    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 Decision2018-04-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-03-13
    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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