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    Summary
    EudraCT Number:2014-000382-41
    Sponsor's Protocol Code Number:WA29330
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-12-22
    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 number2014-000382-41
    A.3Full title of the trial
    A randomized, double-blind, double-dummy active-comparator, multicenter study to evaluate the efficacy and safety of rituximab versus MMF in patients with pemphigus vulgaris
    ESTUDIO MULTICÉNTRICO, ALEATORIZADO, DOBLE CIEGO, CON DOBLE SIMULACIÓN Y COMPARADOR ACTIVO PARA EVALUAR LA EFICACIA Y LA SEGURIDAD DE RITUXIMAB EN COMPARACIÓN
    CON MMF EN PACIENTES CON PÉNFIGO VULGAR
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Rituximab Versus MMF in Patients With Pemphigus Vulgaris
    ESTUDIO RANDOMIZADO, DOBLE CIEGO PARA EVALUAR LA EFICACIA Y SEGURIDAD DE RITUXIMAB EN COMPARACION CON MMF EN PACIENTES CON PÉNFIGO VULGAR
    A.3.2Name or abbreviated title of the trial where available
    PEMPHIX
    PEMPHIX
    A.4.1Sponsor's protocol code numberWA29330
    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 SponsorF. Hoffmann-La Roche Ltd
    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 supportF. Hoffmann-La Roche Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+34913257300
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 MABTHERA®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRituximab
    D.3.2Product code RO0452294/V02
    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 INNRITUXIMAB
    D.3.9.1CAS number 174722-31-7
    D.3.9.2Current sponsor codeRO 0452294
    D.3.9.4EV Substance CodeSUB12570MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    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 CELLCEPT®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMycophenolate mofetil
    D.3.2Product code RO1061443/F02
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMycophenolate mofetil
    D.3.9.1CAS number 128794-94-5
    D.3.9.2Current sponsor codeRO1061443/F02
    D.3.9.4EV Substance CodeSUB03360MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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 placeboConcentrate for solution for infusion
    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 placeboFilm-coated tablet
    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
    Pemphigus Vulgaris (PV)
    Pénfigo vulgar (PV)
    E.1.1.1Medical condition in easily understood language
    Pemphigus Vulgaris (PV)
    Pénfigo vulgar (PV)
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10052802
    E.1.2Term Pemphigus vulgaris
    E.1.2System Organ Class 100000004858
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of rituximab compared with MMF in achieving sustained complete remission, evaluated by the Pemphigus Disease Area Index (PDAI; see Section 3.4.1.1), and assessed at Week 52 in patients with moderate-to-severely active PV
    Evaluar la eficacia de rituximab en comparación con micofenolato mofetilo (MMF) en el logro
    de la remisión completa sostenida, evaluada por el Índice de superficie de la enfermedad
    pénfigo (Pemphigus Disease Area Index, PDAI, véase la Sección 3.4.1.1), y evaluada en la
    semana 52 en pacientes con pénfigo vulgar (PV) moderado a gravemente activo.
    E.2.2Secondary objectives of the trial
    ? To evaluate the efficacy of rituximab compared with MMF, as measured by the time to disease flare after achieving disease control, the duration of sustained complete remission, the total number of disease flares during the treatment period, and the time to initial sustained complete remission
    ? To assess corticosteroid exposure over 52 weeks
    ? To assess the effect of rituximab compared with MMF on health-related quality of life (HRQoL), as measured by the Dermatology Life Quality Index (DLQI)
    ? To assess the effect of rituximab compared with MMF on patients? impression of PV symptoms, as measured by the Patient Global Impression of Change (PGIC) questionnaire
    ? To assess the effect of rituximab compared with MMF on clinician impression of patients? PV symptoms, as measured by the Clinician Global Impression of Change (CGIC) questionnaire
    -Evaluar la eficacia de rituximab en comparación con MMF, según el tiempo transcurrido
    hasta la exacerbación de la enfermedad después de lograr el control de la misma, la duración de la remisión completa sostenida, el número total de exacerbaciones de la enfermedad durante el período de tratamiento y el tiempo hasta la remisión completa sostenida inicial.
    -Evaluar la exposición a los corticoesteroides durante 52 semanas.
    -Evaluar rituximab en comparación con MMF en la calidad de vida relacionada
    con la salud, evaluada según el Índice de calidad de vida dermatológica.
    -Evaluar el efecto del rituximab en comparación con MMF según la impresión del paciente
    de los síntomas de PV, determinado mediante el cuestionario Impresión global del
    cambio realizada por el paciente.
    -Evaluar el efecto del rituximab en comparación con MMF según la impresión del médico
    de los síntomas de PV del paciente, determinado mediante el cuestionario de Impresión
    global de cambio realizada por el médico.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Telemedicine substudy (only in the US)
    For a small proportion of patients (approximately 10 patients across investigational sites), the Sponsor is proposing the use of telemedicine (TM) consultation visits between the patient and the Principal Investigator to make the trial more accessible to this population
    of patients with a rare disease.
    Subestudio de telemedicina (Solo en EEUU)
    Para una pequeña proporción de pacientes (aproximadamente 10 pacientes en centros
    seleccionados), el promotor propone el uso de visitas de telemedicina (TM) de consulta entre
    el paciente y el investigador principal para que el ensayo resulte más accesible a esta población de pacientes con una enfermedad poco común.
    E.3Principal inclusion criteria
    ? Age 18?75 years
    ? Signed Informed Consent Form
    ? Confirmed diagnosis of PV within the previous 24 months, based on the presence of the following: histological features of acantholysis via skin or mucosal biopsy and tissue-bound IgG antibodies by direct immunofluorescence on the surface of affected epithelium
    ? Presence of moderate-to-severely active disease, defined as at least 6 lesions that last more than 1 week or ? 3% body surface involvement, including cutaneous and/or mucosal lesions
    ? Mucosal or cutaneous PDAI activity score of ? 3 and overall PDAI score of 15?45 (moderate-to-severely active disease)
    ? Receiving standard-of-care corticosteroids consisting of 60?120 mg/day PO prednisone or equivalent (1.0 ? 1.5 mg/kg/day) and, in the judgment of the investigator, expected to benefit from the addition of immunosuppressive therapy
    ? For women who are not postmenopausal (? 12 months of non?therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 12 months after the last dose of study treatment
    Abstinence is acceptable only if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
    Barrier methods must always be supplemented with the use of a spermicide.
    Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, established, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices.
    ? For men: agreement to remain abstinent or use a condom during the treatment period and for at least 12 months after the last dose of study treatment and agreement to refrain from donating sperm during this same period
    Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
    ? Agreement to avoid excessive exposure to sunlight during study participation
    ? Able to comply with the study protocol, in the investigator?s judgment
    -Tener entre 18 y 75 años de edad.
    -Formulario de consentimiento informado firmado.
    -Diagnóstico confirmado de PV en los 24 meses anteriores, teniendo en cuenta todo lo que
    sigue: características histológicas de acantólisis obtenidas por medio de una biopsia de piel
    o de la mucosa y anticuerpos IgG adheridos al tejido mediante inmunofluorescencia directa
    en la superficie del epitelio afectado.
    -La presencia de enfermedad moderada a gravemente activa, definida como al menos
    6 lesiones que duran más de 1 semana o comprometen ? 3 % de la superficie corporal, que
    incluyen lesiones cutáneas y/o de las mucosas.
    -Puntuación de la actividad cutánea o de las mucosas según el PDAI ? 3 y puntuación
    general según el PDAI de 15-45 (enfermedad moderada a gravemente activa).
    -Estar recibiendo corticoesteroides que forman parte del estándar de atención, que
    consisten en 60-120 mg/día de prednisona por v.o. ó equivalente (1,0-1,5 mg/kg/día) y,
    según criterio del investigador, se espera que reciba algún beneficio de la adición de un
    tratamiento inmunodepresor.
    -Para las mujeres que no son postmenopáusicas (? 12 meses de amenorrea no inducida por
    tratamiento) o quirúrgicamente estériles (ausencia de ovarios y/o útero): acuerdo para mantener
    la abstinencia sexual o utilizar dos métodos anticonceptivos adecuados, que incluyan al menos
    un método con un tasa de fracaso < 1 % por año, durante el período de tratamiento y durante al
    menos 12 meses después de la última dosis del tratamiento del estudio
    La abstinencia sexual es aceptable solo si es coherente con el estilo de vida preferido y
    habitual del paciente. La abstinencia sexual periódica (por ejemplo, métodos de
    calendario, ovulación, sintotérmico o posovulación) y la marcha atrás no son métodos
    anticonceptivos aceptables.
    Los métodos de barrera siempre deben ser complementados con el uso de un
    espermicida.
    Los ejemplos de métodos anticonceptivos con una tasa de fracaso < 1 % por año
    incluyen la ligadura de trompas, esterilización masculina, implantes hormonales
    establecidos, el uso adecuado de anticonceptivos hormonales orales o inyectables
    combinados y ciertos dispositivos intrauterinos.
    -Para los hombres: comprometerse a mantener la abstinencia sexual o a usar un
    preservativo durante el período de tratamiento y durante al menos 12 meses después de la
    última dosis del tratamiento del estudio y comprometerse a no donar esperma durante este
    mismo período.
    La abstinencia sexual es aceptable solo si es coherente con el estilo de vida preferido y
    habitual del paciente. La abstinencia sexual periódica (por ejemplo, métodos de
    calendario, ovulación, sintotérmico o posovulación) y la marcha atrás no son métodos
    anticonceptivos aceptables.
    -Comprometerse a evitar la exposición excesiva a la luz solar durante la participación en
    el estudio.
    -Capacidad para cumplir con el protocolo del estudio, según el criterio del investigador.
    E.4Principal exclusion criteria
    ?Diagnosis of pemphigus foliaceus or evidence of paraneoplastic pemphigus or other non-PV autoimmune blistering disease
    ? History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies, or known hypersensitivity to any component of rituximab
    ? Known hypersensitivity or contraindication to MMF, mycophenolic acid, polysorbate, or oral corticosteroids
    ? Lack of peripheral venous access
    ? Pregnant or lactating, or intending to become pregnant during the study Women who are not postmenopausal (? 12 months of non?therapy-induced amenorrhea) or surgically sterile must have a negative result from a serum pregnancy test or a urine pregnancy test with a sensitivity of ? 50 mU/mL within 1 week prior to randomization.
    ? Participated in another interventional clinical trial within 28 days prior to randomization
    ? Use of any investigational agent within 28 days or 5 elimination half-lives prior to randomization (whichever is the longer)
    ? Significant cardiovascular or pulmonary disease (including obstructive pulmonary disease)
    ?Evidence of any new or uncontrolled concomitant disease that, in the investigator?s judgment, would preclude patient participation, including but not limited to nervous system, renal, hepatic, endocrine, malignant, or gastrointestinal disorders
    ? Any concomitant condition that required treatment with oral or systemic corticosteroids within 12 weeks prior to randomization
    ? Treatment with IV Ig, plasmapheresis, or other similar procedure within 8 weeks prior to randomization
    ? Treatment with immunosuppressive medications (e.g., azathioprine, MMF) within 1 week prior to randomization
    ? Treatment with cyclophosphamide within 12 weeks prior to randomization
    ? History of or currently active primary or secondary immunodeficiency, including known history of HIV infection and other severe Immunodeficiency blood disorders
    ? Known active infection of any kind (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks prior to screening, or completion of oral anti-infectives within 2 weeks prior to randomization; entry into this study may be reconsidered once the infection has fully resolved.
    ?History of or current cancer, including solid tumors, hematologic malignancies, and carcinoma in situ (except complete excision of basal cell of the skin and squamous cell carcinoma of the skin that have been treated or excised and cured.)
    ?Currently active alcohol or drug abuse, or history of alcohol or drug abuse within 24 weeks prior to screening
    ?Major surgery within 4 weeks prior to randomization, excluding diagnostic surgery
    ?Treatment with rituximab or a B cell-targeted therapy (e.g., anti-CD20, anti CD22, or anti-BLyS) within 12 months prior to randomization
    ?Treatment with a live or attenuated vaccine within 28 days prior to randomization; it is recommended that a patient’s vaccination record and the need for immunization prior to study entry be carefully investigated.
    ?Evidence of abnormal liver enzymes or hematology laboratory values
    ?Positive test results for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) serology at screening
    -Diagnóstico de pénfigo foliáceo o evidencia de pénfigo paraneoplásico u otra enfermedad
    autoinmunitaria distinta del PV con formación de ampollas.
    -Pacientes con antecedentes de reacción alérgica grave o anafiláctica a anticuerpos
    monoclonales humanizados o murinos, o hipersensibilidad conocida a cualquier componente del rituximab.
    -Hipersensibilidad conocida o contraindicación a MMF, ácido micofenólico, polisorbato o
    corticoesteroides orales.
    -Ausencia de acceso venoso periférico.
    -Embarazo o lactancia, o intención de quedar embarazada durante el estudio.
    Las mujeres que no son posmenopáusicas (? 12 meses de amenorrea no inducida por
    un tratamiento) o quirúrgicamente estériles deben obtener un resultado negativo en una
    prueba de embarazo en suero o una prueba de embarazo en orina con una sensibilidad de ?50 mU/ml en la semana antes de la asignación aleatoria.
    -Participación anterior en otro ensayo clínico intervencionista en los 28 días anteriores a la
    asignación aleatoria.
    -El uso de cualquier medicamento en fase de investigación en los 28 días o 5 semividas de
    eliminación antes de la asignación aleatoria (lo que sea más largo).
    -Enfermedad cardiovascular o pulmonar significativa (que incluye enfermedad pulmonar
    obstructiva).
    -Evidencia de cualquier enfermedad concomitante nueva o no controlada que, según criterio
    del investigador, impediría la participación del paciente, incluidas, entre otras, trastornos
    del sistema nervioso, renal, hepático, endocrino, neoplasias o gastrointestinales.
    -Cualquier afección concomitante que requiere tratamiento con corticoides orales o
    sistémicos en las 12 semanas previas a la asignación aleatoria.
    -Tratamiento con inmunoglobulina (Ig) i.v., plasmaféresis u otro procedimiento similar en las
    8 semanas anteriores a la asignación aleatoria.
    -Tratamiento con medicamentos inmunodepresores (por ejemplo, azatioprina, MMF) en la
    semana anterior a la asignación aleatoria.
    -Tratamiento con ciclofosfamida en las 12 semanas previas a la asignación aleatoria.
    -Presencia o antecedentes de inmunodeficiencia primaria o secundaria activa, incluido el
    antecedente conocido de infección por VIH y otros trastornos hemáticos graves que causan
    inmunodeficiencia.
    -Infección activa conocida de cualquier clase (sin incluir las infecciones micóticas del lecho
    ungueal) o cualquier episodio importante de infección que requiera hospitalización o
    tratamiento con antibióticos i.v. en las 4 semanas previas a la selección, o haber terminado
    antibióticos orales en las 2 semanas previas a la asignación aleatoria.
    Puede volver a considerarse la entrada en este estudio una vez que la infección haya
    desaparecido por completo.
    -Presencia o antecedentes de cáncer, que incluye tumores sólidos, neoplasias
    hematológicas y carcinoma in situ (excepto la escisión completa de carcinoma basocelular
    o epidermoide que ha sido tratado o extirpado y curado).
    -Consumo actual de drogas o alcohol, o antecedentes de drogadicción o alcoholismo en las
    24 semanas previas a la selección.
    -Cirugía mayor en las 4 semanas anteriores a la asignación aleatoria; excluye cirugía de
    diagnóstico.
    -Tratamiento con rituximab o tratamiento dirigido a los linfocitos B (por ejemplo, anti-CD20,
    antiCD22 o anti-BLyS) en los 12 meses previos a la asignación aleatoria.
    -Tratamiento con una vacuna de virus vivos o atenuados en los 28 días previos a la
    asignación aleatoria.
    Se recomienda analizar cuidadosamente el registro de vacunación de un paciente y la
    necesidad de inmunización antes de la entrada en el estudio.
    -Evidencia de valores anormales de laboratorio de las enzimas hepaticas o de los valores hematologicos.
    -Resultados positivos en la serología del antígeno de superficie del virus de la hepatitis B
    (HBsAg), anticuerpo del núcleo del virus de la hepatitis B (HBcAb) o el virus de la hepatitis
    C (VHC) realizada en la selección.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of patients who achieve a sustained complete remission without experiencing an event that constitutes treatment failure, as measured at Week 52. Sustained complete remission is defined as achieving healing of lesions with no new active lesions (i.e., PDAI activity score of 0) while on 0 mg/day prednisone or equivalent, and maintaining this response for a total of at least 16 consecutive weeks, during the 52-week treatment period.
    Proporción de pacientes que logran una remisión completa sostenida sin experimentar un
    acontecimiento que constituya el fracaso del tratamiento, según se evalúe en la semana 52.
    La remisión completa sostenida se define como el logro de la curación de las lesiones
    sin nuevas lesiones activas (es decir, puntuación de actividad de 0 según el PDAI)
    mientras el paciente recibe 0 mg/día de prednisona o equivalente, y el mantenimiento
    de esta respuesta durante un total de al menos 16 semanas consecutivas, durante el
    período de tratamiento de 52 semanas.
    E.5.1.1Timepoint(s) of evaluation of this end point
    week 52
    Semana 52
    E.5.2Secondary end point(s)
    - Time to disease flare
    - Duration of sustained complete remission
    - Total number of diseases flares during the treatment period
    - Cumulative oral corticosteroid dose (prednisone or equivalent) over the treatment period
    - Time to initial sustained complete remission
    - Change in health-related quality of life (HRQoL), as measured by the Dermatology Life Quality Index (DLQI) score from baseline to Week 52
    - Change in patients impression of PV symptoms as measured by the Patients' Global Impression of Change (PGIC) score from baseline to Week 52
    - Change in clinician impression of patients? PV symptoms as measured by the CGIC score from baseline to Week 52
    -Tiempo hasta la exacerbación de la enfermedad.
    -Duración de la remisión completa sostenida.
    -Número total de exacerbaciones de la enfermedad durante el período de tratamiento.
    -Dosis acumulativa de corticoesteroides orales (prednisona o equivalente) durante el
    período de tratamiento.
    -Tiempo hasta la remisión completa sostenida inicial.
    -Cambios en la HRQoL, según la puntuación del DLQI, desde los valores iniciales hasta la
    semana 52.
    -Cambio en la impresión de los pacientes de los síntomas de PV, según la puntuación del
    PGIC desde el inicio hasta la semana 52.
    -Cambio en la impresión del médico de los síntomas de PV del paciente, según la
    puntuación del CGIC desde el inicio hasta la semana 52.
    E.5.2.1Timepoint(s) of evaluation of this end point
    week 52
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of Life, optional biomarker analysis
    Calidad de vida, analisis opcional de biomarcadores
    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 No
    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 EEA22
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Australia
    Canada
    France
    Germany
    Israel
    Italy
    Spain
    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 the study is defined as the date when the last patient, last visit (LPLV) occurs. LPLV is expected to occur approximately 2 years after the last patient is enrolled, assuming a 52-week treatment period and a 48-week SFU period for the last patient.
    El final del estudio se define como la fecha en que tenga lugar la UVUP. Se espera que la
    UVUP se produzca aproximadamente 2 años después de la inscripción del último paciente,
    suponiendo un período de tratamiento de 52 semanas y un período de SFU de 48 semanas
    para el último paciente.
    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 months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    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: 93
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 31
    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 35
    F.4.2.2In the whole clinical trial 124
    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)
    The Sponsor will offer post-trial access to the study drug rituximab free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, as outlined in the protocol (section 4.3.4 Post-Trial Access to Rituximab)
    El promotor ofrecerá acceso al fármaco Rituximab después del ensayo de manera gratuita a los pacientes elegibles de acuerdo con la Política
    global sobre el acceso continuo al producto medicinal en fase de investigación del grupo Roche como se explica en el protocolo (sección 4.3.4 Acceso al rituximab después del ensayo)
    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 Decision2015-03-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-02-18
    P. End of Trial
    P.End of Trial StatusCompleted
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