E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Kidney transplantation
Epstein Barr virus |
Transplantation rénale et virus Epstein Barr |
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E.1.1.1 | Medical condition in easily understood language |
Kidney transplantation
Epstein Barr virus |
Transplantation rénale et virus Epstein Barr |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
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 our study is to evaluate the efficacy of early infusion of Rituximab in the prevention of EBV primary infection and post-transplant lymphoproliferative disorder (PTLD) occurrence in adult EBV negative kidney transplant recipients transplanted with an EBV positive donor. |
Evaluer l’efficacité d’une perfusion précoce de Rituximab dans la prévention de la primoinfection EBV et du LPT chez le patient adulte EBV séronégatif transplanté avec un donneur EBV séropostitif. |
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E.2.2 | Secondary objectives of the trial |
-The occurrence of PTLD during the 5 post-transplant years
-The occurrence of post-transplant EBV primary infection during the 5 post-transplant years
-The kinetics of post-transplant EBV replication
-The clinical presentation of EBV primary infection
-The incidence of post-transplant EBV seroconversion during the 5 post-transplant years
-The post-transplant immune reconstitution kinetics
-The kidney allograft function and graft survival during the 5 post-transplant years
-The recipient survival during the 5 post-transplant years
-The tolerance of Rituximab
-The incidence of opportunistic infections and malignancies during the 5 years after transplantation
-The incidence of BK virus and Cytomegalovirus (CMV) infections post-transplantation
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-L’incidence du LPT
-L’incidence de la primoinfection EBV
-La cinétique de la réplication de l’EBV
-La présentation clinique de la primoinfection EBV
-L’incidence de la séroconversion EBV post-transplantation
-La cinétique de la reconstitution immunitaire lymphocytaire
-La fonction du greffon rénal et la survie du greffon
-La survie du patient
-La tolérance du Rituximab
-L’incidence d’infections opportunistes et de cancers
-L’incidence d’infection à BK virus et à Cytomegalovirus (CMV)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Adult patients (age ≥18 years at transplantation)
-Kidney and kidney pancreas simultaneous transplantation
-EBV seronegative patients (IgG anti EBNA, IgG anti VCA and IgM anti VCA negative) (from 6 months before transplantation to the day of transplantation, included)
-Patient who have given written informed consent
-Negative pregnancy test and use of contraception during all the study
-EBV positive donor
-Patient affiliated to a social security scheme
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-Patients de plus de 18 ans affiliés à un régime de protection sociale
-Patients transplantés du rein et/ou rein-pancréas
-Patients EBV séronégatifs (IgG anti-EBNA, IgG anti-VCA et IgM anti-VCA négatifs) au moment de la transplantation
-Patients ayant donné leur consentement écrit
-Test de grossesse négatif (β-HCG dosage) et utilisation d’une contraception tout au long de l’étude
-Donneur EBV positif
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E.4 | Principal exclusion criteria |
-Patient with known HBV active infection
-Hypersensitivity to the active substance or to murine proteins, or to any of the other excipients
-Active severe infection
-Severe Immune deficiency
-Severe cardiac insufficiency
-Pregnant or lactating women
-Women of child bearing potential unless they are using an acceptable birth control methods
-Patient under judicial protection or under guardianship
-Patient currently participating in another clinical trial investigating drugs. Observational studies are not considered as an exclusion criterion
-Any form of substance abuse, psychiatric disorder or condition, which, in the opinion of the investigator, is incompatible with the participation in the study
-Unlikely to comply with the visits scheduled in the protocol
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-Sujet avec infection VHB active connue
-Hypersensibilité à la substance active ou aux protéines murines, ou à l'un des autres excipients
-Infection sévère active
-Immunodéficience sévère
-Insuffisance cardiaque sévère
-Femme enceinte ou allaitante
-Femme en âge de procréer sans contraception efficace
-Sujet sous sauvegarde de justice
-Sujet sous tutelle ou curatelle
-Sujet inclus dans une autre étude de recherche clinique. Les études observationnelles ne sont pas considérées comme critère d’exclusion
-Toute forme de toxicomanie, de trouble ou d'affection psychiatrique qui, de l'avis de l'investigateur, est incompatible avec la participation à l'étude
-Patients risquant de ne pas se conformer aux visites prévues dans le protocole
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E.5 End points |
E.5.1 | Primary end point(s) |
1 year incidence of a composite criteria: EBV primary infection assessed by a positive blood EBV viral load and/or EBV seroconversion ; and/or occurrence of a post-transplant lymphoproliferative disorder |
L’incidence à 1 an d’un critère composite : primoinfection EBV évaluée par PCR sanguine et/ou séroconverison et/ou la survenue d’un syndrome lymphoprolifératif |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year after transplantation |
1 an après la transplantation |
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E.5.2 | Secondary end point(s) |
-1, 2, 3, 4 and 5 years incidence of PTLD after kidney transplantation
-Incidence of primary EBV infection evaluated by EBV viremia (PCR blood test) at M1, M2, M3, M6, M12, M24, M36, M48, M60 and EBV seroconversion at M1, M3, M6, M12, M24, M36, M48, M60.
-Delay of occurrence of primary EBV infection
-Symptoms of EBV primary infection
-CD19/CD20 reconstitution at M3, M6, M12, M24
-Graft loss at M1, M2, M3, M6, M12, M24, M36, M48, M60
-Allograft kidney function evaluated by CKD-EPI formula at M1, M2, M3, M6, M12, M24, M36, M48, M60
-Recipient survival at M1, M2, M3, M6, M12, M24, M36, M48, M60
-Incidence of opportunistic infections and malignancies at M1, M2, M3, M6, M12, M24, M36, M48, M60
-Incidence of BKV viremia (PCR blood test) M1, M3, M6, M12 and M24
-Delay of BKV viremia
-Incidence of CMV viremia (PCR blood test) at M1, M3, M6, M12 and M24
-Delay of CMV viremia
-Treatment tolerance: allergic reaction, neutropenia
-AE/SAE
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-Incidence du syndrome lymphoprolifératif à 1, 2, 3, 4 et 5 ans post-transplantation
-Incidence de primoinfection EBV évaluée par la virémie EBV (PCR sanguine) à 1 , 2, 3, 6, 12, 24, 36, 48 et 60 mois post-transplantation et la séroconversion EBV à 1, 3, 6, 12, 24, 36, 48 et 60 mois post-transplantation
-Symptomatologie de le primoinfection EBV et son délai de survenue
-Reconstitution lymphocytaire CD19/CD20 à 3, 6, 12 et 24 mois post-transplantation
-Survie du patient et du greffon
-Evaluation de la fonction du greffon rénal par la formule CKD-EPI à 1, 2, 3, 6, 12, 24, 36, 48 et 60 mois post-transplantation
-Incidence d’infections opportunistes et de malignité à 1, 2, 3, 6, 12, 24, 36, 48 et 60 mois post-transplantation
-Incidence de l’infection à BK virus évaluée par PCR sanguine à 1, 3, 6, 12 et 24 mois post-transplantation
-Incidence de l’infection à CMV évaluée par PCR sanguine à 1, 3, 6, 12 et 24 mois post-transplantation
-Tolérance du traitement par Rituximab, recueil des effets secondaires et des effets secondaires graves
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
at several diffents timepoint |
à beaucoup de moment différents ( cf secondary endpoint) |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
pas de traitement specifique |
no specific treatment |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
pas de traitement spécifique |
no specific treatment |
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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 | 20 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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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Last visit of the last subject undergoing the trial |
Dernière visite du dernier sujet inclus |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |