E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients will be those receiving a living-related kidney transplant |
pazienti che rispondono ai criteri standard per ricevere un trapianto di rene da donatore vivente |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10023439 |
E.1.2 | Term | Kidney transplant rejection |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 |
This a pilot, explorative study to define the safety and biological/mechanistic effect of the systemic intravenous infusion of syngeneic ex-vivo expanded MSCs in living-related kidney transplant recipients (one or two HLA haplotype mismatches) under basiliximab/low-dose RATG induction therapy and maintenance immunosuppressive drugs with the ultimate objective to test the feasibility of safely achieving graft tolerance in a subsequent efficacy pilot study. Indeed, to complement the research with a clinical portion that document operational tolerance, a pilot efficacy study of safely achieving kidney graft tolerance after complete withdrawal of maintenance immunosuppressive therapy will follow pending on the fact that the results of biological/mechanistic tests will document that MSC infusion allows the development of an immune microenvironment permissive to graft tolerance. |
definire l efficacia dell infusione peritrapianto di MSC singeniche nell indurre tolleranza in pazienti con trapianto di rene da donatore vivente. La condizione di tolleranza e' definita come assenza di episodi di rigetto acuto nel primo anno dalla sospensione della terapia immunosoppressiva che viene intrapresa dopo 12 mesi dal trapianto. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female patients - Aged 18 or older - Non-HLA identical with the donor (one or two haplotype mismatches) - First kidney transplant - Capable of understanding the purpose and risk of the study - Written informed consent |
Maschi e femmine di eta' superiore ai 18 anni; - Non-HLA identici con il donatore (uno o due mismatches); - Primo trapianto di rene; - Capacita' di comprendere gli obiettivi e i rischi dello studio; - Consenso informato scritto |
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E.4 | Principal exclusion criteria |
MSC donor positive for HIV-1, HIV-2, HBV, HCV, Syphilis. - Specific contraindication to MSC infusion - Any clinical relevant condition that might affect study participation and/or study results - Pregnant women and nursing mothers - Unwillingness or inability to follow study protocol in the investigator s opinion |
Controindicazioni specifiche all infusione di MSC; - Qualsiasi condizione clinica rilevante che possa interferire con la partecipazione allo studio o i risultati dello studio stesso; - Gravidanza ed allattamento; - Riluttanza o incapacita', secondo il parere dello sperimentatore, di seguire quanto previsto dal protocollo di studio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare changes in the immunophenotype and ex-vivo T-cell functional tests from samples of peripheral blood and measurement in the urine of messenger RNA for FoxP3, a functional factor for regulatory T lymphocytes in kidney transplant recipients give or not syngeneic (from the recipient) MSC infusion under basiliximab/low-dose RATG induction therapy and maintenance immunosuppressive treatment with low-dose cyclosporine (CsA) plus low-dose mycophenolate mofetil (MMF). |
Valutare le variazioni nel fenotipo immunologico e nei test funzionali ex-vivo sulle cellule T isolate da campioni di sangue periferico e le variazioni nelle misure di RNA messaggero urinario per FoxP3 (un fattore funzionale per le cellule T regolatrici) in pazienti con trapianto di rene che ricevono o non ricevono l infusione di MSC singeniche. I pazienti ricevono terapia di induzione con Basiliximab/basse dosi di RATG e terapia di mantenimento con basse dosi di CsA in associazione a basse dosi di MMF. |
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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 | 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) | Yes |
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) | 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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |