E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Kidney Transplantation
BKV infection |
Transplantation rénale
Infection à BK virus |
|
E.1.1.1 | Medical condition in easily understood language |
Kidney Transplantation
BKV infection |
Transplantation rénale
Infection à BK virus |
|
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 the study is to investigate the impact of a preventive administration of IVIG on the incidence of BKV viremia (> 3.5 log10 copies/mL in at least two consecutive samples) in patients with low titers of neutralizing antibodies (NAbs) against the donor’s BKV strain at the time of transplantation. |
Étudier l'impact d'une administration préventive d'IgIV sur l'incidence de la virémie à BK virus chez les patients présentant de faibles taux d'anticorps neutralisants (NAbs) contre la souche BK du donneur au moment de la transplantation. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess in a prospective cohort, the kinetics of BKV NAbs, the incidence of BKV diseases, graft rejection episodes, graft survival, the incidence of TTV viremia, the evolution of B and T-cell repertoire against BKV, the tolerance of IVIG; and assess BKV NAb concentration in administered IVIG. |
Évaluer, dans une cohorte prospective, la cinétique des taux de BKV NAbs, l'incidence des maladies liées au BK virus, les épisodes de rejet de greffe, la survie du greffon, l'incidence de la virémie TTV, l'évolution du répertoire des cellules B et T contre BKV, la tolérance des IgIV, et évaluer la concentration de BKV NAb dans les IgIV administrés. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Adult patients (≥ 18 years)
- Kidney transplant recipients, including multiple organ transplant patients
- Patients able to understand the purpose and the risks of the study, fully informed and having written informed consent
- Women of child bearing potential or intends to become pregnant, unless they are using an effective method of birth control* and a βHCG blood test negative
- Affiliated to a medical insurance scheme |
- Patient adulte (≥ 18 ans)
- Patient greffé rénal, y compris les patients ayant subi une transplantation d’organes multiples
- Patient capable de comprendre le but et les risques de l’étude, ayant reçu une information complète et ayant donné son consentement écrit, libre et éclairé
- Test de grossesse négatif
- Affilié à un régime d’assurance maladie |
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E.4 | Principal exclusion criteria |
- BKV nephropathy during a previous transplantation in the past 5 years
- HLA and ABO-incompatible kidney transplant recipients undergoing desensitization with rituximab and/or plasmapheresis before transplantation or susceptible to receive such therapy after transplantation
- Patients with high risk of post- transplant Focal Segmental glomerulosclerosis recurrence
- Patient with hyperprolinemia
- Contraindications to the use to IVIg: hypersensitivity to the active substance or to any excipients or human immunoglobulins, especially in patients with antibodies against IgA
- Pregnant or breast feeding women
- Adults under guardianship or limited guardianship
- Currently participating in another clinical trial investigating drugs (observational studies are not considered as an exclusion criterion)
Patients with high risk of thrombosis
Patients with isolated IgA deficiency
|
- Néphropathie à BK virus lors d’une transplantation antérieure au cours des 5 dernières années
- Receveur d’une transplantation HLA ou ABO-incompatible nécessitant un traitement de désensibilisation par Rituximab et/ou par plasmaphérèse avant la transplantation ou susceptibles de recevoir un tel traitement après transplantation
- Patient présentant un risque élevé de glomérulosclérose segmentaire focale post-transplantation
- Patient présentant une hyperprolinémie
- Allergie ou intolérance connue aux IgIV
- Femmes enceintes ou allaitantes
- Patient sous tutelle, curatelle ou sauvegarde de justice
- Patient participant actuellement à un autre essai clinique portant sur des médicaments (les études observationnelles ne sont pas considérées comme un critère d'exclusion)
Patients présentant un risque élevé de thrombose
Patients présentant une déficience isolée en IgA
|
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the incidence of BKV viremia (> 3.5 log10 copies/mL in at least two consecutive samples) 6 months after transplantation. |
Incidence de virémie à BK Virus (> 4 log10 copies/mL) 6 mois après la transplantation |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 months after transplantation |
6 mois après la transplantation |
|
E.5.2 | Secondary end point(s) |
The secondary endpoints are:
- BKV NAb titers at the day (D) of transplantation (D0), and D10 ,D31, D52, M3, M6 and M12
- Incidence of BKV viruria at D10, D31, D52, M3, M6 and M12
- Incidence of BKV viremia > 3.5 log10 copies/mL in at least two consecutive samples at D0, D10, D31, D52, M3, M6 and M12
- Incidence of TTV viremia at D0, D10, D31, D52, M3, M6 and M12
- Evolution of T and B-cell repertoire against BKV at D0, D31, D52, M3, M6 and M12
- Incidence of BKV nephropathy at M3, M6, and M12
- Time of occurrence and duration of viruria, viremia and BKVAN
- Genotype of replicative BKV
- The predictive value of BKV Nab titers pre-transplantation for BKV replication after transplantation
- GFR evaluated by CKD EPI formula at M3, M6 and M12
- Percentage of patients with donor specific antibodies (DSA) at M3 and M12
- Incidence of biopsy proved antibody mediated rejection at M3 and M12 according to Banff classification
- Incidence of biopsy proved acute cellular rejection at M3 and M12 according to Banff classification
- Patient and graft survival at M12
- Tolerance of IVIG, adverse and severe adverse effects |
Critères d’évaluation secondaires :
- Taux de NAb anti BKV le jour de la transplantation (J0), et à J10, J31, J52, M3, M6 et M12
- Incidence de virurie BK Virus à J10, J31, J52, M3, M6 et M12
- Incidence de virémie BK Virus (> 4log10 copies/mL) à J0, J10, J31, J52, M3, M6 et M12
- Incidence de virémie TTV à J0, J10, J31, J52, M3, M6 et M12
- Evolution du répertoire des cellules T et B contre BK virus à J0, J10, J31, J52, M3, M6 et M12
- Incidence de néphropathie à BK Virus à M3, M6 et M12
- Apparition et durée de la virurie, de la virémie et de la néphropathie à BK virus
- Génotype du BK virus réplicatif
- Valeur prédictive des taux de BKV Nab pré-transplantation pour la réplication de BKV après transplantation
- GFR évalué par la formule CKD EPI à M3, M6 et M12
- Pourcentage de patients présentant des anticorps spécifiques du donneur (DSA) à M3 et M12
- Incidence de rejets médiés par anticorps à M3 et M12 selon la classification de Banff
- Incidence de rejet cellulaire aigu prouvé par biopsie à M3 et M12 selon la classification de Banff
- Survie du patient et du greffon à M12
- Tolérance aux IgIV, effets indésirables et effets indésirables graves |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day of transplantation
Days 10, 31 and 52 after transplantation
Months 3, 6 and 12 after transplantation |
Jour de la transplantation
Jours 10, 31 et 52 après la transplantation
Mois 3, 6 et 12 après la transplantation |
|
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 | 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 | 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 | No |
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 | 21 |
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
|
Last visit of the last subject undergoing the trial |
Dernière visite du dernier sujet en cours d'étude |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |