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    Summary
    EudraCT Number:2017-001055-30
    Sponsor's Protocol Code Number:MK8228-002
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Restarted
    Date on which this record was first entered in the EudraCT database:2017-12-12
    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 number2017-001055-30
    A.3Full title of the trial
    A Phase III, Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of MK-8228 (Letermovir) Versus Valganciclovir for the Prevention of Human Cytomegalovirus (CMV) Disease in Adult Kidney Transplant Recipients
    Estudio de fase III, aleatorizado, doble ciego y controlado con un comparador activo para evaluar la eficacia y la seguridad de MK-8228 (letermovir) frente a valganciclovir para la prevención de la enfermedad por el citomegalovirus (CMV) humano en pacientes adultos que han recibido un trasplante renal
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    LET vs VGCV for Prevention of CMV disease in Kidney Transplant Recipients
    LET comparado con VGCV para la prevención de la enfermedad por CMV en receptores de trasplante renal
    A.3.2Name or abbreviated title of the trial where available
    LET vs VGCV for Prevention of CMV disease in Kidney Transplant Recipients
    LET comparado con VGCV para la prevención de la enfermedad por CMV en receptores de trasplante renal
    A.4.1Sponsor's protocol code numberMK8228-002
    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 SponsorMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    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 supportMerck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMerck Sharp & Dohme de España S.A.
    B.5.2Functional name of contact pointInvestigación Clínica
    B.5.3 Address:
    B.5.3.1Street AddressC/ Josefa Valcárcel, 38
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28037
    B.5.3.4CountrySpain
    B.5.4Telephone number+34913210600
    B.5.5Fax number+34913210590
    B.5.6E-mailensayos_clinicos@merck.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/12/999
    D.3 Description of the IMP
    D.3.1Product nameLETERMOVIR
    D.3.2Product code MK-8228
    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 INNLETERMOVIR
    D.3.9.1CAS number 917389-32-3
    D.3.9.3Other descriptive nameLETERMOVIR
    D.3.9.4EV Substance CodeSUB90389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number240
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/12/999
    D.3 Description of the IMP
    D.3.1Product nameLETERMOVIR
    D.3.2Product code MK-8228
    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 INNLETERMOVIR
    D.3.9.1CAS number 917389-32-3
    D.3.9.3Other descriptive nameLETERMOVIR
    D.3.9.4EV Substance CodeSUB90389
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number480
    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 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 Valganciclovir
    D.2.1.1.2Name of the Marketing Authorisation holderAccord Healthcare Limited
    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.3.4Pharmaceutical 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 INNVALGANCICLOVIR
    D.3.9.1CAS number 175865-60-8
    D.3.9.4EV Substance CodeSUB00007MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number450
    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 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 Cymevene (Ganciclovir)
    D.2.1.1.2Name of the Marketing Authorisation holderroche polska sp. z o.o
    D.2.1.2Country which granted the Marketing AuthorisationPoland
    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.3.4Pharmaceutical 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 INNGANCICLOVIR
    D.3.9.1CAS number 82410-32-0
    D.3.9.4EV Substance CodeSUB07881MIG
    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.IMP: 5
    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 nameLETERMOVIR
    D.3.2Product code MK-8228
    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 INNLETERMOVIR
    D.3.9.1CAS number 917389-32-3
    D.3.9.3Other descriptive nameLETERMOVIR
    D.3.9.4EV Substance CodeSUB90389
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    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 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: 6
    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 Acyclovir
    D.2.1.1.2Name of the Marketing Authorisation holderTEVA Pharmaceuticals USA, Inc.
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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.3.4Pharmaceutical form Capsule
    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 INNACICLOVIR SODIUM
    D.3.9.1CAS number 69657-51-8
    D.3.9.3Other descriptive nameACICLOVIR SODIUM
    D.3.9.4EV Substance CodeSUB00284MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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: 7
    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 Acic (Acyclovir)
    D.2.1.1.2Name of the Marketing Authorisation holderHexal
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Powder 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 INNACICLOVIR SODIUM
    D.3.9.1CAS number 69657-51-8
    D.3.9.3Other descriptive nameACICLOVIR SODIUM
    D.3.9.4EV Substance CodeSUB00284MIG
    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 placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 4
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 5
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    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
    Prevention of CMV disease in D+/R- kidney transplant recipients
    Prevención de la enfermedad por CMV en receptores D+/R- de trasplante renal
    E.1.1.1Medical condition in easily understood language
    Cytomegalovirus (CMV) is a common virus in the herpes family of viruses that can infect anyone. CMV disease is a common complication in patients receiving organ transplatation, which could be fatal.
    Citomegalovirus(CMV)es un virus común en la familia del herpes, puede infectar a cualquiera. Enfermedad por CMV es complicación común en pacientes que reciben trasplante de órgano, podría ser fatal.
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10011831
    E.1.2Term Cytomegalovirus infection
    E.1.2System Organ Class 10021881 - Infections and infestations
    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 letermovir (LET) versus valganciclovir (VGCV), as measured by the proportion of participants with adjudicated CMV disease through 52 weeks post-transplant.
    Evaluar la eficacia de letermovir (LET) comparado con valganciclovir (VGCV), medida mediante la proporción de participantes con enfermedad por CMV validada, durante 52 semanas después del trasplante
    E.2.2Secondary objectives of the trial
    1. To evaluate the efficacy of LET versus VGCV, as measured by the proportion of participants with adjudicated CMV disease through 28 weeks post-transplant.
    2. To evaluate the efficacy of LET versus VGCV, as measured by the time to onset of adjudicated CMV disease through 52 weeks post-transplant.
    3. To evaluate the safety and tolerability of LET versus VGCV.
    1. Evaluar la eficacia de LET comparado con VGCV, medida mediante la proporción de participantes con enfermedad por CMV validada, durante 28 semanas después del trasplante.
    2. Evaluar la eficacia de LET comparado con VGCV, medida mediante el tiempo transcurrido hasta el comienzo de la enfermedad por CMV validada, durante 52 semanas después del trasplante
    3. Evaluar la seguridad y tolerabilidad de LET comparado con VGCV
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Merck will conduct Future Biomedical Research on DNA (blood and plasma) specimens collected during this clinical trial. Additionally, samples will be collected from a selected group of participants for Viral resistance studies. Such research is for biomarker and testing and to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.
    Merck realizará una futura investigación biomédica con las muestras obtenidas para tal finalidad durante este ensayo clínico. Dichas investigaciones podrán incluir análisis genéticos (ADN), (suero, plasma) Estas investigaciones tendrán por objeto el análisis de biomarcadores con el fin de abordar aspectos nuevos que no se describen en otras partes del protocolo (como parte del ensayo principal) y solo se llevarán a cabo en muestras de los participantes que hayan otorgado el consentimiento correspondiente. El objetivo de la obtención/conservación de muestras para futura investigación biomédica consiste en estudiar e identificar biomarcadores que proporcionen información a los científicos sobre las enfermedades y/o sus tratamientos. El objetivo esencial es utilizar tal información para desarrollar vacunas/fármacos más seguros y eficaces y/o para garantizar que los participantes reciban la dosis correcta del fármaco/vacuna adecuados en el momento preciso.
    E.3Principal inclusion criteria
    1. Have a documented negative serostatus for CMV (ie, recipient CMV IgG seronegative [R-]) within 90 days prior to randomization.
    2. Anticipate receiving a first allograft kidney from a CMV IgG seropositive (D+) donor at the time of screening AND have received a first allograft kidney from a documented D+ donor at the time of randomization.
    3. Be within 0 (ie, day of transplantation) to 7 days (inclusive) post-kidney transplant at the time of randomization.
    4. Be ≥18 years of age on day of signing informed consent.
    5. A male participant must agree to use contraception as detailed in Appendix 5 of the protocol during the treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.
    6. A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies:
    a. Not a woman of childbearing potential (WOCBP), as defined in Appendix 5
    OR
    b. A WOCBP who agrees to follow the contraception guidance in Appendix 5 during the treatment period and for at least 90 days after the last dose of study treatment.
    7. Understand the study procedures, alternative treatment available, and risks involved with the study, and he/she voluntarily agrees to participate by giving written informed consent and is willing to adhere to dose and visit schedules. Participant may also provide consent for Future Biomedical Research. However, the participant may participate in the main study without participating in Future Biomedical Research.
    8. Be able to read, understand, and complete questionnaires and diaries.
    1. Seroestado negativo documentado para el CMV (es decir, receptor con seronegatividad de la IgG del CMV [R-]) en los 90 días previos a la aleatorización.
    2. Recepción prevista de un primer aloinjerto renal de un donante con seropositividad de la IgG del CMV (D+) en el momento de la selección Y recepción de un primer aloinjerto renal de un donante D+ documentado en el momento de la aleatorización.
    3. Encontrarse en el período de 0 (es decir, día del trasplante) a 7 días (inclusive) después del trasplante renal en el momento de la aleatorización.
    4. Tener una edad mínima de 18 años el día de firma del consentimiento informado.
    5. Los varones deben comprometerse a utilizar métodos anticonceptivos tal como se detalla en el Apéndice 5 de este protocolo durante el período de tratamiento y hasta, como mínimo, 90 días después de la última dosis del tratamiento del estudio, así como a abstenerse de donar semen durante este período.
    6. Una mujer podrá participar en el estudio si no está embarazada (véase el Apéndice 5), no está amamantando y cumple al menos una de las condiciones siguientes:
    a. No ser una mujer en edad fértil (MEF), según se define en el Apéndice 5.
    O
    b. Si es una MEF, comprometerse a seguir las indicaciones en materia de anticonceptivos del Apéndice 5 durante el período de tratamiento y durante al menos 90 días después de la última dosis del tratamiento del estudio.
    7. Comprender los procedimientos del estudio, los tratamientos alternativos disponibles y los riesgos asociados al estudio y aceptar voluntariamente participar otorgando su consentimiento informado por escrito y expresando su disposición a cumplir los calendarios de dosis y de visitas. El participante también podrá otorgar su consentimiento para la futura investigación biomédica. No obstante, el paciente podrá participar en el estudio principal sin necesidad de hacerlo en la futura investigación biomédica.
    8. Ser capaz de leer, comprender y cumplimentar los cuestionarios y diarios.
    E.4Principal exclusion criteria
    1. Received a previous solid organ transplant or HSCT.
    2. Is a multi-organ transplant recipient (eg, kidney-pancreas).
    3. Has a history of CMV disease or suspected CMV disease within 6 months prior to randomization.
    4. Has suspected or known hypersensitivity to active or inactive ingredients of LET formulations, VGCV, GCV, and/or ACV formulations.
    5. Is on dialysis at the time of randomization.
    6. Has post-transplant renal function of CrCl ≤10 mL/min at randomization (measured locally). For this exclusion criterion, CrCl will be calculated using the Cockcroft-Gault equation using the most recently obtained and available serum creatinine value collected within 3 calendar days prior to and including the day of randomization and after the conclusion of any clinically warranted (at the discretion of the investigator) post-transplant dialysis.
    7. Has Child-Pugh Class C severe hepatic insufficiency (Appendix 8 of the protocol) at screening.
    8. Has both moderate hepatic insufficiency AND moderate-to-severe renal insufficiency at screening.
    9. Has any uncontrolled infection on the day of randomization.
    10. Has documented positive results for human immunodeficiency virus antibody (HIV-Ab) test at any time prior to randomization, or for hepatitis C virus antibody (HCV-Ab) and with detectable HCV ribonucleic acid (RNA) or hepatitis B surface antigen (HBsAg) within 90 days prior to randomization.
    11. Requires mechanical ventilation, or is hemodynamically unstable, at the time of randomization.
    12. Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy.
    13. Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through at least 90 days following cessation of study therapy.
    14. Is expecting to donate eggs or sperm starting from the time of consent through at least 90 days following cessation of study therapy.
    15. Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or put the participant at undue risk, as judged by the investigator, such that it is not in the best interest of the participant to participate in this study.
    16. Has exclusionary laboratory value at the screening visit, as listed in the protocol.
    17. Has received within 30 days prior to randomization or plans to receive during the study any of the following anti-CMV IgG antibody treatment or anti CMV drug therapy including:
    a. Cidofovir
    b. CMV hyper-immune globulin
    c. Any investigational CMV antiviral agent/biologic therapy.
    18. Has received within 7 days prior to randomization or plans to receive during the study any of the following anti-CMV drug therapy including:
    a. LET
    b. GCV
    c. VGCV
    d. Foscarnet
    e. ACV (at doses > 3200 mg PO per day or > 25 mg/kg IV per day)
    f. Valacyclovir (at doses > 3 g PO per day)
    g. Famciclovir (at doses > 1500 mg PO per day)
    19. Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
    20. Is taking or plans to take any of the prohibited medications listed in the protocol (see Section 7.7).
    21. Is currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5× half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing on this study. Participants previously treated with an investigational monoclonal antibody will be eligible to participate after a 150 day washout period.
    22. Has previously participated in this study or any other study involving LET.
    23. Has previously participated or is currently participating in any study involving administration of a CMV vaccine or another CMV investigational agent, or is planning to participate in a study of a CMV vaccine or another CMV investigational agent during the course of this study.
    24. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this study.
    1. Haber recibido anteriormente un trasplante de órgano sólido o TCPH.
    2. Ser un receptor de varios órganos (p. ej., riñón-páncreas).
    3. Antecedentes de enfermedad por CMV o sospecha de enfermedad por CMV en los 6 meses previos a la aleatorización.
    4. Hipersensibilidad presunta o confirmada a alguno de los componentes activos o inactivos de las formulaciones de LET, VGCV y/o ACV.
    5. Estar recibiendo diálisis en el momento de la aleatorización
    6. Tener una función renal posterior al trasplante de CrCl ≤ 10 ml/min en el momento de la aleatorización (medida localmente). Para este criterio de exclusión, la CrCl se calculará empleando la ecuación de Cockcroft-Gault y el valor de creatinina sérica obtenido más recientemente y disponible que se haya recogido en los 3 días naturales previos al día de la aleatorización inclusive y después de la finalización de cualquier diálisis posterior al trasplante clínicamente justificada (en opinión del investigador).
    7. Insuficiencia hepática grave de clase C de Child-Pugh (Apéndice 8) en la selección.
    8. Insuficiencia hepática moderada E insuficiencia renal moderada a grave en la selección.
    9. Infección no controlada el día de la aleatorización.
    10. Resultados positivos documentados de anticuerpos contra el virus de la inmunodeficiencia humana (Ac-VIH) en cualquier momento antes de la aleatorización o anticuerpos contra el virus de la hepatitis C (Ac-VHC) y con ácido ribonucleico (ARN) del VHC o antígeno de superficie del virus de la hepatitis B (HBsAg) detectable en los 90 días previos a la aleatorización.
    11. Necesidad de ventilación mecánica o presencia de inestabilidad hemodinámica en el momento de la aleatorización.
    12. Antecedentes de neoplasias malignas ≤ 5 años antes de firmar el consentimiento informado, salvo carcinoma basocelular o espinocelular de la piel o cáncer in situ de cuello uterino o carcinoma in situ debidamente tratados, o en fase de evaluación por otra neoplasia maligna activa o presunta.
    13. Pacientes embarazadas o que tengan previsto quedarse embarazadas, estén dando de mamar o prevean hacerlo desde el momento de firmar el consentimiento hasta al menos 90 días después de la suspensión del tratamiento del estudio.
    14. Previsión de donar óvulos o semen desde el momento de firmar el consentimiento hasta al menos 90 días después de la suspensión del tratamiento del estudio.
    15. Antecedentes o indicios actuales de cualquier proceso, tratamiento, anomalía analítica u otra circunstancia que pueda confundir los resultados del estudio, interferir en la participación del paciente durante todo el estudio o suponer un riesgo excesivo a criterio del investigador, por lo que no le conviene al paciente participar en este estudio.
    16. Existencia en la visita de selección de alguno de los valores analíticos que son motivo de exclusión, como se indica en el protocolo.
    17. Recepción en los 30 días previos a la aleatorización o previsión de recibir durante el estudio cualquiera de los siguientes tratamientos con anticuerpos anti-IgG del CMV o tratamientos con fármacos anti-CMV, como:
    a. Cidofovir
    b. Hiperinmunoglobulina contra el CMV
    c. Cualquier antiviral/tratamiento biológico contra el CMV en investigación.
    18. Recepción en los 7 días previos a la aleatorización o previsión de recibir durante el estudio cualquiera de los siguientes tratamientos con fármacos anti-CMV, como:
    a. LET
    b. GCV
    c. VGCV
    d. Foscarnet
    e. ACV (en dosis > 3200 mg al día por vía oral o 25 mg/kg al día por vía IV)
    f. Valaciclovir (en dosis > 3 g al día por vía oral)
    g. Famciclovir (en dosis > 1500 mg al día por vía oral)
    19. Ser, en el momento de firmar el consentimiento informado, consumidor de drogas o tener antecedentes recientes (en el último año) de alcoholismo o toxicomanía.
    20. El paciente está utilizando o tiene previsto utilizar cualquiera de los medicamentos prohibidos que se enumeran en el protocolo (véase la sección 7.7.).
    21. Participación actual o participación previa en un estudio sobre un compuesto o dispositivo en investigación no aprobado en los 28 días, o el equivalente a 5 semividas del compuesto en investigación (excepto anticuerpos monoclonales), lo que suponga más tiempo, previos a la administración inicial en este estudio. Podrán participar pacientes tratados previamente con un anticuerpo monoclonal en investigación tras un período de lavado de 150 días.
    22. Participación previa en este estudio o en cualquier otro estudio de LET.
    23. Participación previa o actual en un estudio que suponga la administración de una vacuna contra el CMV u otro fármaco experimental contra el CMV o participación prevista en un estudio de una vacuna contra el CMV u otro fármaco experimental contra el CMV durante este estudio.
    24. El participante o un familiar directo (por ejemplo, cónyuge, padre/madre o tutor legal, hermano o hijo) forma parte del personal del centro de investigación o del promotor implicado directamente en este estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Proportion of participants with adjudicated CMV disease through 52 weeks post-transplant
    Proporción de participantes con enfermedad por CMV validada, durante 52 semanas después del trasplante.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Proportion of participants with adjudicated CMV disease through 52 weeks post-transplant.
    Proporción de participantes con enfermedad por CMV validada, durante 52 semanas después del trasplante.
    E.5.2Secondary end point(s)
    1. 28 weeks post-transplant
    2. 52 weeks post-transplant
    1. 28 semanas después del trasplante.
    2. 52 semanas después del trasplante.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Proportion of participants with adjudicated CMV disease through 28 weeks post transplant.
    2. Time to onset of adjudicated CMV disease through 52 weeks post-transplant.
    1. proporción de participantes con enfermedad por CMV validada, durante 28 semanas después del trasplante.
    2. Tiempo hasta el comienzo de la enfermedad por CMV validada durante 52 semanas después del trasplante
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Acyclovir (ACV) as Standard Prophylaxis
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA36
    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
    Austria
    Belgium
    Canada
    Colombia
    France
    Germany
    Hungary
    Italy
    Mexico
    New Zealand
    Poland
    Spain
    United Kingdom
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months40
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months40
    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: 510
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 90
    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 state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 229
    F.4.2.2In the whole clinical trial 600
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Ninguno
    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 Decision2018-04-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-19
    P. End of Trial
    P.End of Trial StatusRestarted
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