E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transplant-associated cytomegalovirus (CMV) infection |
TRANSPLANTE ASOCIOADO A INFECCIÓN POR CITOMEGALOVIRUS |
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E.1.1.1 | Medical condition in easily understood language |
Cytomegalovirus (CMV) infection that is associated with kidney transplants. |
citomegalovirus (CMV) asociado con los trasplantes de riñón. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011831 |
E.1.2 | Term | Cytomegalovirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058881 |
E.1.2 | Term | Cytomegalovirus viremia |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10047438 |
E.1.2 | Term | Viral infectious disorders |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10021881 |
E.1.2 | Term | Infections and infestations |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10011827 |
E.1.2 | Term | Cytomegaloviral infections |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
?To evaluate the safety of multiple IV doses of MCMV5322A/MCMV3068A given to cytomegalovirus (CMV) seronegative recipients of a renal transplant from a CMV seropositive donor. ?To determine the clinical activity of multiple IV doses of MCMV5322A/MCMV3068A given to CMV-seronegative recipients of a renal transplant from a CMV-seropositive donor. |
?Evaluar la seguridad de múltiples dosis i.v. de MCMV5322A/MCMV3068A administradas a pacientes seronegativos para el citomegalovirus (CMV) receptores de trasplante renal procedente de un donante seropositivo para el virus. ?Determinar la actividad clínica de múltiples dosis i.v. de MCMV5322A/MCMV3068A administradas a pacientes seronegativos para el CMV receptores de trasplante renal procedente de un donante seropositivo para el virus. |
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E.2.2 | Secondary objectives of the trial |
?To characterize the pharmacokinetic (PK) profile of multiple doses of MCMV5322A/MCMV3068A ?To characterize the immunogenic potential of MCMV5322A/MCMV3068A by measuring anti-MCMV5322A and anti-MCMV3068A antibodies |
?Caracterizar el perfil farmacocinético (FC) de múltiples dosis de MCMV5322A/MCMV3068A ?Caracterizar el potencial inmunogénico de MCMV5322A/MCMV3068A midiendo los anticuerpos anti MCMV5322A y anti MCMV3068A |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
?Patient is scheduled to receive a primary or secondary renal allograft from a living or cadaveric donor. ?Patient is seronegative for CMV ?Ability and willingness to provide written informed consent(s) and to comply with the requirements of the protocol ?Men and women aged > 18 years ?Female patients of childbearing potential must have negative urine pregnancy test result on Day 1. ?For women who are not postmenopausal or surgically sterile (defined as absence of ovaries and/or uterus): agreement to remain completely abstinent or use two methods of contraception at all times |
?El paciente está a la espera de recibir un alotrasplante renal primario o secundario de un donante vivo o muerto. ?El paciente es seronegativo para el CMV ?Capacidad y voluntad de proporcionar su consentimiento informado por escrito y de cumplir con los requisitos del protocolo ?Hombres y mujeres de al menos 18 años de edad ?Las pacientes femeninas en edad fértil deben someterse a una prueba de embarazo en orina con resultado negativo el Día 1, antes de la infusión. ?Para las mujeres que no son postmenopáusicas (definidas como mujeres de al menos 46 años de edad y con 24 meses de amenorrea para la que no hay otra causa patológica o fisiológica obvia) o quirúrgicamente estériles (definido como ausencia de ovarios o útero): aceptan abstenerse por completo de mantener relaciones sexuales o utilizar dos métodos anticonceptivos en todas las ocasiones |
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E.4 | Principal exclusion criteria |
?Patient is suspected of having CMV disease. ?Patient has received anti-CMV therapy within the 30 days prior to screening. (Exceptions are the use of acyclovir, valacyclovir, or famciclovir for up to 10 days duration for treatment of acute herpes simplex or herpes zoster or patients receiving acyclovir or valacyclovir at doses to suppress herpes zoster). ?Patients who have received intravenous immunoglobulin (IVIG) within 3 months before transplantation or with expectation of receiving IVIG at time of transplantation or in the 3 months after transplantation ?Patients who have received B cell-depleting therapies (rituximab) within 3 months before transplantation or with the expectation of receiving rituximab at the time of transplantation or in the 3 months after transplantation. ?Patient is receiving a multi-organ transplant (e.g., liver or pancreas in addition to kidney). ?Active or chronic hepatic or hepatobiliary disease (including known Gilbert?s syndrome) or elevations in a hepatic transaminase (AST or ALT) or bilirubin (total or free) - 2 - upper limit of normal (ULN). ?Patient is unlikely or unwilling to be available for follow-up for the full 24-week duration of the study. ?Female patients who are pregnant, plan to become pregnant during the study, or who are breastfeeding ?History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins or human-derived immunoglobulin preparations ?Active treatment for untreated tuberculosis or other infectious conditions that are significant in the judgment of the investigator |
?Si se sospecha que el paciente padece una enfermedad por CMV. ?El paciente ha recibido un tratamiento contra el CMV en los 30 días anteriores a la selección (excepto el uso de aciclovir, valaciclovir o famciclovir durante un máximo de 10 días para el tratamiento del herpes simple agudo o el herpes zóster o pacientes que reciben aciclovir o valaciclovir a las dosis necesarias para suprimir el herpes zóster). ?Pacientes que han recibido inmunoglobulina intravenosa (IGIV) en los tres meses anteriores al trasplante o esperan recibir IGIV en el momento del trasplante o en los tres meses posteriores ?Pacientes que han recibido tratamientos que reducen los linfocitos B (rituximab) en los tres meses anteriores al trasplante o que esperan recibir rituximab en el momento del trasplante o en los tres meses posteriores ?Pacientes que reciben un trasplante multiorgánico (por ejemplo, hígado o páncreas además de riñón) ?Hepatopatía o enfermedad hepatobiliar activa o crónica (incluyendo el síndrome de Gilbert) o elevaciones en las transaminasas hepáticas (AST o ALT) o la bilirrubina (total o libre) de al menos dos veces el límite superior de la normalidad (LSN). ?El paciente probablemente no estará disponible para el seguimiento, o no desea estarlo, durante las 24 semanas de duración del estudio. ?Las pacientes que están embarazadas, planean un embarazo durante el estudio o están en periodo de lactancia ?Antecedentes de reacciones alérgicas, anafilácticas u otras reacciones de hipersensibilidad graves a anticuerpos híbridos o humanizados o proteínas de fusión o preparados de inmunoglobulinas derivadas de plasma humano ?Tratamiento activo para una tuberculosis no tratada u otras enfermedades infecciosas significativas a juicio del investigador |
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E.5 End points |
E.5.1 | Primary end point(s) |
?Detectable CMV viremia within the first 12 weeks after transplantation, defined as at least one CMV viral load > 150 copies/mL as assessed by the central laboratory. |
?Viremia por CMV detectable en las primeras 12 semanas tras el trasplante, definida como al menos una carga viral de CMV > 150 copias/ml, según la evaluación del laboratorio central. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
see section E.5.1 |
Ver sección E.5.1 |
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E.5.2 | Secondary end point(s) |
?Detectable CMV viremia within the first 24 weeks after transplantation, defined as at least one CMV viral load > 150 copies/mL as assessed by the central laboratory. ?Time to detectable CMV viremia, defined as time from transplant to first CMV viral load >150 copies/mL as assessed by the central laboratory ?Viral load at first detection of CMV viremia (> 150 copies/mL) as assessed by the central laboratory ?Peak viral load on or following first detection of CMV viremia (> 150 copies/mL) as assessed by the central laboratory ?Initiation of preemptive antiviral therapy during the first 12 weeks after transplantation ?Initiation of preemptive antiviral therapy during the first 24 weeks after transplantation ?Time to initiation of first use of preemptive antiviral therapy ?Duration of first use of preemptive antiviral therapy initiated during the first 12 weeks after transplantation ?Duration of all use of preemptive antiviral therapy initiated during the first 24 weeks after transplantation ?CMV disease (CMV syndrome or tissue-invasive disease as defined in Appendix 3) during the first 24 weeks after transplantation ?Change in CMV serostatus as assessed by the central laboratory |
?Viremia por CMV detectable en las primeras 24 semanas tras el trasplante, definida como al menos una carga viral de CMV > 150 copias/ml, según la evaluación del laboratorio central. ?Tiempo hasta alcanzar una viremia por CMV detectable, definida como el tiempo desde el trasplante hasta la primera carga viral de CMV > 150 copias/ml según la evaluación del laboratorio central ?Carga viral al detectar por primera vez la viremia por CMV (> 150 copias/ml) según la evaluación del laboratorio central ?Carga viral máxima al detectar o después de detectar por primera vez la viremia por CMV (> 150 copias/ml) según la evaluación del laboratorio central ?Inicio del tratamiento antiviral presintomático durante las primeras 12 semanas tras el trasplante ?Inicio del tratamiento antiviral presintomático durante las primeras 24 semanas tras el trasplante ?Tiempo hasta el primer uso de tratamiento antiviral presintomático ?Duración del primer uso de tratamiento antiviral presintomático iniciado durante las primeras 12 semanas tras el trasplante. ?Duración del uso total de tratamiento antiviral presintomático iniciado durante las primeras 24 semanas tras el trasplante. ?Enfermedad por CMV (síndrome por CMV o infección invasora de tejidos según se define en el Apéndice 3) durante las primeras 24 semanas tras el trasplante ?Cambio en el estado serológico para el CMV según la evaluación del laboratorio central |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See section E.5.2.1 |
Ver sección E.5.1 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Netherlands |
Norway |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
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The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later. LPLV is expected to occur approximately 6 months after the last patient is enrolled. |
El final de este estudio se define como la fecha en la que se produce la última visita del último paciente (UVUP) o la fecha en la que se reciben los últimos datos puntuales del último paciente necesarios para el análisis estadístico o el seguimiento de seguridad, lo que ocurra más tarde. Se espera que la UVUP se produzca aproximadamente 6 meses después de que se reclute al último paciente. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |