E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
kidney transplant patients |
PACIENTES TRANSPLANTADOS RENALES |
|
E.1.1.1 | Medical condition in easily understood language |
kidney transplant patients |
PACIENTES TRANSPLANTADOS RENALES |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
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 |
The main objective of the study is to demonstrate the utility and safety of the IFN-? ELISPOT marker for the stratification of kidney transplant recipients into low and high IS regimens. The enrichment study will test non-inferiority of low IS regimen compared to high IS regimen, assuming 10% of BPAR at 6-months in the control group, and allowing a non-inferiority limit of maximum 15%. |
EL OBJETIVO PRINCIPAL DEL ENSAYO ES DEMOSTRAR LA UTILIDAD Y SEGURIDAD DEL MARCADOR IFN-? ELISPOT PARA LA ESTRATIFICACIÓN DE LOS PACIENTES TRANSPLANTADOS RENALES A RECIBIR UN REGIMEN INMUNOSUPRESOR MÁS INTESNSO O MÁS SUAVE.EL ESTUDIO PROBARÁ LA NO INFERIORIDAD DEL TRATAMIENTO MÁS SUAVE EN COMPARACIÓN CON EL TRATAMIENTO MÁS INTENSO, ASUMIENDO UN 10% DE RECHAZO AGUDO PROBADO MEDIANTE BIOPSIA RENAL EN EL BRAZO CONTROL Y PERMITIENDO UN LÍMITE DE NO INFERIORIDAD MÁXIMO DEL 15%. |
|
E.2.2 | Secondary objectives of the trial |
- To investigate differences across treatment arms in the following secondary outcomes: e.g. eGFR (ml/min) at 6 and 12 months etc. - Health economics, H-R QoL and treatment cost (cost/benefit) at 1, 3, 6, 12 and 24 months. |
- INVESTIGAR LAS DIFERENCIAS ENTRE LOS BRAZOS DE TRATAMIENTO EN RELACIÓN A LOS OBJETIVOS SECUNDARIOS. - ANÁLISIS DE COSTE BENEFÍCIO Y DE CALIDAD DE VIDA A LOS 1, 3, 6, 12 Y 24 MESES POST TR. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Men and women, age ?18 years. 2) Subject must be a recipient of a first renal transplant from a deceased or living donor. 3) Subject must have a current documented PRA <20% and no detectable anti-class I and II HLA antibodies by solid phase assay (Luminex®). 4) Subject is willing to provide signed written informed consent. 5) Women of Childbearing Potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea ? 12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL]. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of clinical trial. |
1) HOMBRES Y MUJERES, EDAD>18 AÑOS. 2) RECEPTORES DE UN PRIMER TRANSPLANTE RENAR DE UN DONANTE VIVO O CADAVER. 3) EL SUJETO DEBE TENER UN PRA ACTUAL Y DOCUMENTADO <20% Y NO PRESENTAR ANTICUERPOS ANTI HLA CLASE I Y/O CLASE II MEDIANTE ENSAYO EN FASE SÓLIDA (LUMINEX). 4) EL SUJETO DEBE PROPORCIONAR SU CONSENTIMIENTO DE FORMA ESCRITA 5) LAS MUJERES EN EDAD FÉRTIL DEBEN UTILIZAR UN MÉTODO ANTICONCEPTIVO ÁLTAMENTE EFECTIVO PARA EVITAR EL EMBARAZO DURANTE TODO EL ENSAYO |
|
E.4 | Principal exclusion criteria |
1) Subjects undergoing renal transplant with a current documented PRA >20% and/or detectable anti-class I and II HLA antibodies by solid phase assay (Luminex®). 2) CDC positive cross match. 3) Subjects receiving an allograft from a donor older than 65 years with elevated creatinine levels and/or treated diabetes. 4) Cold ischemia time (CIT) higher than 24h. 5) Subjects with a prior solid organ transplant (SOT), including renal re-transplantation, or receiving a concurrent SOT. 6) Patients previously treated with daclizumab or basiliximab. 7) Subjects with underlying renal disease of: a. Primary focal segmental glomerulosclerosis. b. Type I or II membranoproliferative glomerulonephritis c. Atypical Haemolytic uremic syndrome (HUS) / thrombotic thrombocytopenic purpura syndrome. 8) Subject with Hepatitis B chronic infection and/or active infection by Hepatitis C virus (positive PCR result) at the moment of transplant. 9) Subjects with known human immunodeficiency virus (HIV) infection. 10) Patients with active systemic infection that requires the continued use of antibiotics. 11) Patients with neoplasia except localized skin cancer receiving appropriate treatment. 12) Patients with severe anemia (hemoglobin < 6g/dl), leucopenia (WBC <2500/mm3), thrombocytopenia (platelets <80.000/mm3). 13) Hemodynamically instable patients even if their hemoglobin level counts > 6 g/dl. 14) Patients with intestinal pathology or severe diarrhoea that can hinder absorption according to medical criteria. 15) Subjects with a known hyper sensibility to any of the drugs used in this protocol. 16) Subjects who have used any investigational drug within 30 days prior to enrolment in this clinical trial. 17) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period, women who are pregnant or breastfeeding or women with a positive pregnancy test on enrolment. 18) Subjects who are legally detained in an official institution |
1) sujetos sometidos a trasplante renal con un PRA> 20% y/o anticuerpos anti-clase I y II de HLA detectables mediante un ensayo de fase sólida (Luminex®). 2) CDC prueba cruzada positiva. 3) Sujetos que recibieron un aloinjerto de un donante mayor de 65 años, con niveles elevados de creatinina y/o diabetes tratada. 4) Tiempo de isquemia fría (CIT) superior a 24h. 5) Sujetos con un trasplante de órgano sólido anterior (SOT), incluyendo re-trasplante renal, o recibir un SOT concurrente. 6) Pacientes previamente tratados con daclizumab o basiliximab. 7) Sujetos con enfermedad renal subyacente de: a. Glomeruloesclerosis focal y segmentaria primaria. b. Tipo I o II glomerulonefritis membranoproliferativa c. Síndrome hemolítico urémico atípico (SUH) / síndrome de púrpura trombocitopénica trombótica. 8) Pacientes con hepatitis B crónica y/o infección activa por el virus de la hepatitis C (PCR resultado positivo) en el momento del trasplante. 9) Sujetos con infección conocida por el virus de la inmunodeficiencia humana (VIH). 10) Pacientes con infección sistémica activa que requiera el uso continuo de antibióticos. 11) Pacientes con neoplasia excepto el cáncer de piel localizada que reciben un tratamiento adecuado. 12) Pacientes con anemia grave (hemoglobina <6 g / dl), leucopenia (leucocitos <2.500 / mm3), trombocitopenia (plaquetas <80.000 / mm3). 13) Pacientes hemodinámicamente inestables incluso si sus recuentos de nivel de hemoglobina> 6 g / dl. 14) Pacientes con patología intestinal o diarrea severa que puede dificultar la absorción según criterio médico. 15) Pacientes con una hipersensibilidad conocida a cualquiera de los fármacos utilizados en este protocolo. 16) Sujetos que han utilizado cualquier fármaco en investigación en los 30 días anteriores a la inscripción en este ensayo clínico. 17) Mujeres potencialmente fértiles que no están dispuestas o no pueden utilizar un método aceptable para evitar el embarazo durante todo el periodo de estudio, las mujeres que están embarazadas o lactantes o con una prueba de embarazo positiva. 18) Los sujetos que están legalmente detenidos en una institución oficial |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The main objective of the study is to demonstrate the utility and safety of the IFN-? ELISPOT marker for the stratification of kidney transplant recipients into low and high IS regimens. The enrichment study will test non-inferiority of low IS regimen compared to high IS regimen, assuming 10% of BPAR at 6-months in the control group, and allowing a non-inferiority limit of maximum 15%. |
EL OBJETIVO PRINCIPAL DEL ENSAYO ES DEMOSTRAR LA UTILIDAD Y SEGURIDAD DEL MARCADOR IFN-? ELISPOT PARA LA ESTRATIFICACIÓN DE LOS PACIENTES TRANSPLANTADOS RENALES A RECIBIR UN REGIMEN INMUNOSUPRESOR MÁS INTESNSO O MÁS SUAVE.EL ESTUDIO PROBARÁ LA NO INFERIORIDAD DEL TRATAMIENTO MÁS SUAVE EN COMPARACIÓN CON EL TRATAMIENTO MÁS INTENSO, ASUMIENDO UN 10% DE RECHAZO AGUDO PROBADO MEDIANTE BIOPSIA RENAL EN EL BRAZO CONTROL Y PERMITIENDO UN LÍMITE DE NO INFERIORIDAD MÁXIMO DEL 15%. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months post-transplantation |
12 meses post transplante renal |
|
E.5.2 | Secondary end point(s) |
To investigate differences across treatment arms in the following secondary outcomes: - eGFR (ml/min) assessed by the CKD-EPI formula at 6 and 12 months - Prevalence of biomarkers* of tolerance/hyporesponsiveness at 3 and 12 months. - Incidence, type, severity, treatment, and outcome of BPAR by 6 and 12 months after transplantation. - Prevalence, type, severity, treatment, and outcome of subclinical rejection by 6 and 12 months after transplantation. - Prevalence of death, and graft loss by 6 and 12 months. - Prevalence of metabolic and cardiovascular co-morbidity (new onset diabetes mellitus (NODAT), dyslipidemias, hypertension) by 12 months. - Prevalence of subjects that remain MMF and steroid-free at 6 and 12 months after transplantation - Prevalence of Acute and chronic histologic lesions assessed by the Bannf?11 score in protocol biopsies at months 3 and 12 post-transplantation. - Prevalence of patients that remain on Therapy at 12 months after transplantation. - Distribution of patients in distinct chronic kidney diseases (CKD) stages by 12 months. - Health economics, H-R QoL and treatment cost (cost/benefit) at 1, 3, 6, 12 and 24 months. |
Investigar las diferencias entre los grupos de tratamiento en los siguientes objetivos secundarios: - FGe (ml / min) evaluada por la fórmula CKD-EPI a los 6 y 12 meses - Prevalencia de biomarcadores * de tolerancia / respuesta menor a los 3 y 12 meses. - Incidencia, tipo, gravedad, tratamiento y resultado de BPAR a los 6 y 12 meses después del trasplante. - Prevalencia, tipo, gravedad, tratamiento y resultado del rechazo subclínico a los 6 y 12 meses después del trasplante. - Prevalencia de la muerte, y la pérdida del injerto a los 6 y 12 meses. - La prevalencia de alteraciones metabólicas y cardiovasculares, comorbilidad (diabetes mellitus nueva aparición (NODAT), dislipidemias, hipertensión) a los 12 meses. - Prevalencia de los sujetos que permanecen MMF y libre de esteroides a los 6 y 12 meses después del trasplante - Prevalencia de lesiones agudas y lesiones histológicas crónicas evaluadas por la puntuación Bannf'11 en biopsias de protocolo en los meses 3 y 12 post-trasplante. -Prevalencia de pacientes que permanecen en terapia a los 12 meses después del trasplante. - Distribución de los pacientes en distintas enfermedades crónicas del riñón (CKD) etapas por 12 meses. - Economía de la salud, de recursos humanos y la calidad de vida-coste del tratamiento (coste / beneficio) a los 1, 3, 6, 12 y 24 meses. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- eGFR (ml/min) assessed by the CKD-EPI formula at 6 and 12 months - Prevalence of biomarkers* of tolerance/hyporesponsiveness at 3 and 12 months. - Incidence, type, severity, treatment, and outcome of BPAR by 6 and 12 months after transplantation. - Prevalence, type, severity, treatment, and outcome of subclinical rejection by 6 and 12 months after transplantation. - Prevalence of death, and graft loss by 6 and 12 months. |
- FGe (ml / min) evaluada por la fórmula CKD-EPI a los 6 y 12 meses - Prevalencia de biomarcadores * de tolerancia / respuesta menor a los 3 y 12 meses. - Incidencia, tipo, gravedad, tratamiento y resultado de BPAR por 6 y 12 meses después del trasplante. - Prevalencia, tipo, gravedad, tratamiento y resultado del rechazo subclínico por 6 y 12 meses después del trasplante. - Prevalencia de la muerte, y la pérdida del injerto a los 6 y 12 meses. |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial 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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |