E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Liver failure: end-stage liver diseases, including cirrhosis, primary liver cancer, fulminant hepatic failure and numerous other metabolic or congenital hepatic diseases.
Kidney failure: end-stage renal diseases. |
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E.1.1.1 | Medical condition in easily understood language |
Liver failure: patient whose liver no longer functions well enough to maintain life.
Kidney failure: patient whose kidneys do not filter the waste or toxins from blood anymore. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050434 |
E.1.2 | Term | Prophylaxis against liver transplant rejection |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050436 |
E.1.2 | Term | Prophylaxis against renal transplant rejection |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 MSC infusion after liver and kidney transplantation.
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E.2.2 | Secondary objectives of the trial |
1.To evaluate patient and graft survivals.
2.To evaluate the effects of MSC on graft function (for LT: bilirubin, INR, transaminases, GGT; for KT: number of post transplant hemodialysis, creatinine).
3.To evaluate biopsy-proven (Banff classification) rejection rates.
4.To evaluate the feasibility and safety of weaning or decreasing immunosuppression.
5.To evaluate recipient’s immune function (T cell blood populations (including T regs) by FACS, TREC quantification, Vβ repertoire diversity, pathogen-specific T cells, anti-organ donor HLA antibodies).
6.To evaluate the potential development of anti-MSC donor HLA antibodies. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients
•Male or female patients between 18 and 75 years of age, who will undergo first KT or whole LT from a cadaveric or DCD organ donor; fertile female patients must use a reliable contraception method;
•Informed consent given by patient or his/next of kin if the patient is unable to give informed consent, for the complete (MSC + follow-up) or partial (no MSC + follow-up) study;
•Successful liver/kidney transplantation, demonstration of organ function (improvement of INR in liver recipients and of creatinine in kidney recipients at 24-36h) and normal graft vasculature at Doppler examination. |
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E.4 | Principal exclusion criteria |
•Past history of malignant disease, with the exception of hepatocarcinoma within the Milan criteria for the Liver Transplantation patients.
•Active uncontrolled infection.
•HIV or HCV positive.
•EBV-negative.
•Retransplantation.
•Combined transplantation.
•Living related transplantation or split liver transplantation.
•Autoimmune disease or expected impossibility to wean immunosuppression (Liver Transplantation) or corticosteroids (Kidney Transplantation).
•Endotracheal intubation.
•Postoperative cardiovascular instability, active hemorrhage, or any other serious clinical complication between transplantation and evaluation for suitability for MSC infusion.
•For Kidney Transplantation: panel reactive antibodies (PRA) >50%. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the safety of MSC infusion after liver and kidney transplantation:
1. infusional toxicity.
2. incidence of infections (bacterial, viral, fungal, parasitic) and cancers (PTLD). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuously for 2 years. |
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E.5.2 | Secondary end point(s) |
1.To evaluate patient and graft survivals.
2.To evaluate the effects of MSC on graft function.
3.To evaluate biopsy-proven (Banff classification) rejection rates.
4.To evaluate the feasibility and safety of weaning or decreasing immunosuppression; 5.To evaluate recipient’s immune function (T cell blood populations (including T regs) by FACS, TREC quantification, Vβ repertoire diversity, pathogen-specific T cells, anti-organ donor HLA antibodies).
6.To evaluate the potential development of anti-MSC donor HLA antibodies. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.Patient and graft survivals; continuously for 2 years
2.Effects of MSC on graft function:
LT: bilirubin, INR, transaminases, GGT, at day 7, months 1, 3, 6, 9, 12.
KT: number of post transplant hemodialysis, creatinine at day 7, months 1, 3, 6, 9, 12.
3.Biopsy-proven (Banff classification) rejection rates at months 3, 6, 9, 12.
4.Feasibility and safety of weaning or decreasing immunosuppression; continuously for 2 years
5.To evaluate recipient’s immune function (T cell blood populations (including T regs) by FACS, TREC quantification, Vβ repertoire diversity, pathogen-specific T cells, anti-organ donor HLA antibodies) at months 1, 2, 3, 4, 6, 9, 12;
6.Potential development of anti-MSC donor HLA antibodies at months 1, 3, 6, 12. |
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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 | 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) | 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 | No |
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 | 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 | 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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The end of the trial will be completed 2 years after the last patient has been enrolled (20 patients and the control group of 20 patients). |
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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 | |
E.8.9.1 | In the Member State concerned days | |