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    Summary
    EudraCT Number:2014-004557-14
    Sponsor's Protocol Code Number:LIFT
    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:2015-12-10
    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 number2014-004557-14
    A.3Full title of the trial
    Prospective randomised marker-based trial to assess the clinical utility and safety of biomarker-guided immunosuppression withdrawal in liver transplantation
    Estudio prospectivo aleatorizado para evaluar la utilidad clínica y la seguridad de la retirada de inmunosupresores basada en biomarcadores en el trasplante hepático.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial to work out how safe it is to gradually withdraw immunosuppressive drugs in people who had a liver transplant
    Estudio de investigación para evaluar la seguridad de la retirada gradual del tratamiento inmunosupresor en pacientes con trasplante de hígado
    A.3.2Name or abbreviated title of the trial where available
    LIFT
    A.4.1Sponsor's protocol code numberLIFT
    A.5.4Other Identifiers
    Name:Sponsor Protocol NumberNumber:ASF/001-01
    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 SponsorKing's College London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNIHR - EME grant
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKing's College London
    B.5.2Functional name of contact pointProf Alberto Sanchez-Fueyo
    B.5.3 Address:
    B.5.3.1Street AddressInstitute of Liver Studies, King?s College Hospital, MRC Transplant Centre, King?s College London
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSE5 9RS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number442032993305
    B.5.6E-mailsanchez_fueyo@kcl.ac.uk
    B.Sponsor: 2
    B.1.1Name of SponsorKing?s College Hospital NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNIHR - EME grant
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationKing's College London
    B.5.2Functional name of contact pointProf. Alberto Sanchez-Fueyo
    B.5.3 Address:
    B.5.3.1Street AddressInstitute of Liver Studies, King?s College Hospital, MRC Transplant Centre, King?s College London
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSE5 9RS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number442032993305
    B.5.6E-mailsanchez_fueyo@kcl.ac.uk
    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.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameTacrolimus
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    Sublingual use
    Nasogastric use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTACROLIMUS
    D.3.9.1CAS number 104987113
    D.3.9.3Other descriptive nameTACROLIMUS MONOHYDRATE
    D.3.9.4EV Substance CodeSUB23141
    D.3.10 Strength
    D.3.10.1Concentration unit µg/kg microgram(s)/kilogram
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number200
    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 Yes
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameMycophenolic acid
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    Nasogastric use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMYCOPHENOLIC ACID
    D.3.9.1CAS number 24280-93-1
    D.3.9.3Other descriptive nameMycophenolate
    D.3.9.4EV Substance CodeSUB09098MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1440
    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: 3
    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.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 nameciclosporin
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    Sublingual use
    Nasogastric use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCyclosporin
    D.3.9.1CAS number 59865-13-3
    D.3.9.3Other descriptive namecyclosporine, cyclosporin, ciclosporin A, cyclosporine A, cyclosporin
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number15
    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: 4
    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.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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.3.4Pharmaceutical 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.3.9.3Other descriptive nameMYCOPHENOLATE MOFETIL
    D.3.9.4EV Substance CodeSUB03360MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Immunosuppression withdrawal in liver transplantation
    Retirada del tratamiento inmunosupresor en trasplante hepático
    E.1.1.1Medical condition in easily understood language
    Withdrawal of drugs which lower the immune system after a liver transplant
    Retirada del tratamiento inmunosuopresor tras trasplante de hígado
    E.1.1.2Therapeutic area Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10024716
    E.1.2Term Liver transplantation
    E.1.2System Organ Class 100000004865
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine if the use of a liver tissue transcriptional test of tolerance to stratify liver recipients prior to immunosuppression (IS) withdrawal accurately identifies operationally tolerant recipients and reduces the incidence of rejection, as compared with a control group in whom IS withdrawal is performed without stratification.
    El objetivo general del estudio es evaluar la utilidad clínica y el balance riesgo/beneficio de la utilización de una prueba transcripcional de tolerancia para estratificar los receptores de trasplante de hígado previa retirada de tratamiento inmunosupresor.
    E.2.2Secondary objectives of the trial
    1) To establish the safety of biomarker-guided IS withdrawal.
    2) To determine the health-economic impact of withdrawing IS in liver transplant recipients and to assess how much this cost is influenced by the use of a diagnostic test of operational tolerance.
    3) To assess the effect of IS withdrawal on the quality of life of liver transplant recipients.
    4) To determine the extent to which IS withdrawal improve drug-related co-morbidities.
    5) To investigate if liver transplant recipients under IS become operationally tolerant over time.
    6) To determine if the presence of donor-specific anti-HLA antibodies influence the success of IS withdrawal, and whether IS withdrawal promotes the development of anti-HLA antibodies in liver transplant recipients.
    7) To explore the association between operational liver transplant tolerance, iron metabolism,immunosenescence, and specific gut microbiome profiles
    1) Establecer la seguridad de la retirada de inmunosupresores (IS) basada en biomarcadores
    2) Determinar el impacto económico en salud de retirar el tto IS en receptores de trasplante hepático y evaluar cómo afecta el coste del uso de una prueba diagnóstica de tolerancia operacional
    3) Evaluar el efecto de retirada de tto IS en la calidad de vida de los receptores de trasplante de hígado
    4) Determinar en qué medida la retirada de tto IS mejora las comorbilidades relacionadas con los fármacos
    5) Investigar si los receptores de trasplante hepático en tto con IS se convierten tolerantes a lo largo del tiempo
    6) Determinar si la presencia de anticuerpos anti-HLA específicos del donante influyen en el éxito de la retirada del tto IS, y si esta promueve el desarrollo de Ac anti-HLA en receptores de trasplante hepático
    7) Explorar la asociación entre tolerancia operacional en trasplante hepático, metabolismo del hierro, inmunosenescencia y perfiles de microbioma intestinal específica
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. At the time of screening: more than 3 years post-transplant if participants are ?50 years old, OR ? 6 years post-transplant if participant age is 18-49 years old.
    2. Recipient of either deceased or living donor liver transplant.
    3. Recipient of single organ transplant only
    4. Liver function tests: direct bilirubin ?17.1 umol/L and ALT ?60 IU/L at the screening visit.
    5. On calcineurin inhibitor (CNI) based maintenance IS and no more than one of the following: Low dose mycophenolic acid (? 1080 mg daily), mycophenolate mofetil (MMF ? 1500 mg daily); or azathioprine ( ? 1500 mg daily); or on mycophenolate/mycopheolic acid monotherapy (effective contraception must be used before beginning mycophenolate therapy, during therapy, and for six weeks following discontinuation of therapy).
    6. Ability to sign informed consent.
    1. Post-trasplantados de más de 3 años de ? 50 años de edad, o post-trasplantados de ? 6 años de 18-49 años de edad en el momento de la preselección
    2. Receptores de trasplante hepático de donante fallecido o vivo.
    3. Receptores de trasplante de órgano único
    4. Pruebas de función hepática: bilirrubina directa ?17.1 µmolL y GPT ?60 ALT UI/L en la visita de screening.
    5. En tratamiento inmunosupresor de mantenimiento con un inhibidor de calcineurina y uno de los siguientes fármacos:
    Ácido micofenolico a dosis bajas (? 1080 mg al día), micofenolato mofetil (MMF ? 1500 mg al día); o azatioprina (? 150mg al día), o micofenolato / ácido micofenolico en monoterapia (deberán utilizarse anticonceptivos de alta eficacia previo inicio del tratamiento con micofenolato, durante el tratamiento, y durante las siguientes 6 semanas tras la discontinuación del tratamiento).
    6. Con capacidad para firmar el consentimiento informado.
    E.4Principal exclusion criteria
    1. Serum positivity for HCV-RNA.
    2. Serum positivity for HIV-1 infection, HBV surface antigen or HBV-DNA.
    3. Immune-mediated liver disease in which IS discontinuation is inadvisable (autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis).
    4. Acute or chronic rejection within the 52 weeks prior to screening.
    5. GFR <40 mL/min (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI be required).
    6. The need for chronic anti-coagulation that cannot be safely discontinued to safely perform for a liver biopsy.
    7. Baseline (screening) liver biopsy showing any of the following: a) acute rejection according to Banff criteria; b) early or late chronic rejection according to Banff criteria; c) inflammatory activity and/or fibrosis in excess of permissive criteria (Table 1) (25) ; f) any other findings that might make participation in the trial unsafe. Elligibility will be determined by the central pathologist.
    8. Patient age <18 years old at the time of transplant.
    9. Pregnant females and females of childbearing age not using effective contraception.
    10. Current illicit drug or alcohol abuse.
    11. Inability to participate in frequent monitoring of liver function (every 3 weeks) and clinical visits during IS withdrawal.
    12. Inability to comply with study directed treatment.
    13. Any medical condition that in the opinion of the principal investigator would interfere with safe completion of the trial.
    14. Participation in another clinical trial during the month prior to enrolment.
    1. Serología positiva para RNA-VHC.
    2. Serología positiva para VIH-1, antígeno de superficie VHB o DNA-VHB.
    3. Enfermedad hepática inmunomediada en la que no esté recomendada la retirada de tratamiento inmunosupresor (hepatitis autoinmune, colangitis esclerosante primaria, cirrosis biliar primaria).
    4. Rechazo agudo o crónico rechazo dentro de las 52 semanas previas al screening.
    5. Tasa de filtrado glomerular < 40 mL/min
    6. En tratamiento con anticoagulantes crónicos que no se puedan retirar para la realización de una biopsia del hígado segura.
    7. Biopsia hepática en la visita basal (screening) que muestre cualquiera de los siguientes eventos: a) rechazo agudo según los criterios de Banff; b) rechazo temprano o tardío crónico según los criterios de Banff; c) actividad inflamatoria y/o fibrosis por encima de los criterios establecidos (ver tabla 1 del protocolo); f) cualquier otro hallazgo que pueda interferir en la seguridad del estudio. La elegibilidad será determinada por el patólogo central.
    8. Paciente de < 18 años de edad en el momento del trasplante.
    9. Mujeres embarazadas y mujeres en edad fértil que no estén utilizando medidas de anticoncepción de alta eficacia.
    10. Consumo actual de alcohol o sustancias ilícitas.
    11. Pacientes con dificultad para cumplir con el seguimiento de la función hepática (cada 3 semanas) y las visitas clínicas establecidas durante la retirada del tratamiento inmunosupresor.
    12. cumplir con el tratamiento según lo establecido por el protocolo.
    13. Cualquier condición médica que en opinión del investigador principal pueda interferir con la seguridad y realización del estudio.
    14. Participación en otro ensayo clínico durante el mes previo a la inclusión en el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is defined as the successful discontinuation of IS with maintainance of normal allograft status as assessed by liver biopsy and liver tests 12 months after IS withdrawal (operational tolerance). For the purposes of validating the clinical usefulness of the tolerance biomarker, successful IS withdrawal is considered the Gold Standard. Since this outcome is strictly restricted to the IS withdrawal process and by definition cannot be observed in Arm B-, the analysis of the primary outcome will be restricted to Arms A and B+.
    La variable principal se define como el éxito en la retirada de tratamiento inmunosupresor con mantenimiento del estado normal del aloinjerto evaluado mediante biopsia hepática y pruebas hepáticas tras los 12 meses posteriores a la retirada del tratamiento inmunosupresor (tolerancia operacional). Dado que la definición de variable principal implica un proceso de retirada de tratamiento inmunosupresor, el análisis de la variable principal se limitará a las ramas A y B+.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 months after IS withdrawal
    12 meses tras la retirada de tratamiento inmunosupresor
    E.5.2Secondary end point(s)
    Rejection (incidence, severity, timing, steroid resistant rejection, chronic rejection).
    Reasons for failure of IS withdrawal.
    Progression of graft fibrosis in tolerant participants and those on maintenance IS.
    Graft loss.
    All?cause mortality.
    Proportion of tolerant participants remaining free of rejection at 3 years post IS withdrawal.
    Renal function at 1, 2 and 3 years after enrollment.
    Change in co-morbidities associated with IS use (hypertension, cardiovascular risk profile, diabetes mellitus, hyperlipidemia, malignancy).
    HrQOL changes associated with IS withdrawal
    Pharmacoeconomic impact of IS withdrawal


    The secondary mechanistic endpoints of the trial are:
    Intra-hepatic and systemic iron parameters.
    Time post-trasnplant, age, sex and type of IS.
    Markers of immune-exhaustion on blood and liver tissue.
    Gut microbiome profile.
    Blood and intra-hepatic lymphocite subsets (including regulatory T cells).
    Development of anti-HLA antibodies(before and after initiation of IS withdrawal).
    - Rechazo (incidencia, gravedad, tiempo, rechazo resistente a esteroides, rechazo crónico).
    - Motivos de fracaso de la retirada de tratamiento inmunosupresor
    - Progresión de la fibrosis del injerto en participantes tolerantes y en aquellos que mantienen el tratamiento inmunosupresor.
    - Pérdida del injerto
    - Mortalidad por cualquier causa
    - Proporción de participantes tolerantes libres de rechazo a los 3 años tras la retirada del tratamiento inmunosupresor.
    - Función renal al año, 2 ay 3 años tras la inclusión en el estudio
    - Cambios en la co-morbilidad asociada al uso del tratamiento inmunosupresor (hipertensión, riesgo cardiovascular, diabetes mellitus, hiperlipidemia, malignidad).
    - Cambios en el cuestionario de calidad de vida asociados a la retirada del tratamiento inmunosupresor.
    - Impacto farmacoeconómico de la retirada del tratamiento inmunosupresor.

    Las variables secundarias patogénicas del estudio son:
    - Parámetros de hierro intra-hepático y sistémico.
    - Tiempo de post-trasplante, edad, sexo y tipo de tratamiento inmunosupresor.
    - Marcadores de desgaste inmunológico en sangre y tejido hepático.
    - Perfil de microbioma intestinal.
    - Subpoblaciones limfocitarias en sangre e intra-hepáticas (incluidas las células reguladoras T).
    - Desarrollo de anticuerpos anti-HLA (antes y después del inicio de la retirada del tratamiento inmunosupresor).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the trial
    a lo largo de todo el estudio
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Immunosuppression withdrawal performed without the guidance of the stratifying biomarker test
    E.8.2.4Number of treatment arms in the trial3
    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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    Última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years6
    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: 148
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 148
    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 state148
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 148
    F.4.2.2In the whole clinical trial 148
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    No different from the expected normal treatment
    No difiere de los habituales en esta condición
    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 Decision2015-12-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-11-16
    P. End of Trial
    P.End of Trial StatusOngoing
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