E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Side effects of life-long immunosuppressive medication account for major morbidity after pediatric liver transplantation and impair quality of life. In-vivo and in-vitro studies have shown that MSCs may act beneficial in the setting of solid organ transplantation, suppressing immune-active cells directed against the graft while promoting tolerance-inducing Tregs and graft regeneration. Finally, immunosuppressive medication can be used in lower dose with beneficial toxicity profile. |
|
E.1.1.1 | Medical condition in easily understood language |
Children after liver transplantation |
Kinder nach Lebertransplantation |
|
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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024716 |
E.1.2 | Term | Liver transplantation |
E.1.2 | System Organ Class | 100000004865 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety and Tolerance of Donor-specific Mesenchymal Stem Cell therapy in context of pediatric liver transplantation
|
Sicherheit und Verträglichkeit von Spender-spezifischen MSCs in der Anwendung bei Kindern nach Lebertransplantation durch Lebendspende |
|
E.2.2 | Secondary objectives of the trial |
Efficacy Hematologic and immunologic function |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent (patients, both parents and / or legal guardian) 2. age ≥ 8 weeks and ≤ 18 years 3. undergoing living donor liver transplantation for chronic terminal liver failure 4. Body weight > 5kg
|
|
E.4 | Principal exclusion criteria |
1. No suitability of the living-donor 2. Pregnant or breastfeeding 3. If appropriate: no use of adequate contraception 4. Acute liver failure; highly urgent transplantations 5. Receiving any form of solid organ retransplantation 6. Multi-Organ-Transplantations 7. Active autoimmune disease, e.g. autoimmune hepatitis 8. Pre-existing renal failure with eGFR < 50 ml/min/1.73 m2 or requiring hemodialysis 9. Reduced pulmonary function (children older than 6 years: FEV1 and FVC < 70% of age-appropriate norm) 10. History of pulmonary embolism 11. Pulmonary hypertension and / or right ventricular load in echocardiography 12. Cardiac function: left ventricular shortening fraction (FS) < 25% 13. Clinically significant systemic infections 14. Critical care treatment like mechanical ventilation, dialysis or vasopressor agents. 15. HIV seropositive, HTLV seropositive, Hepatitis B/C seropositive 16. Hepato-biliary malignancies or history of any extra-hepatic malignancy 17. Thrombophilia 18. Budd-Chiari syndrome 19. Pre-existent thrombosis of portal vein 20. Doppler-sonographic evidence for relevant porto-systemic shunts, e.g. persistent Ductus Venosus 21. Cold ischemia time > 90 min 22. Known allergy to DMSO
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence, timing and severity of any clinical complication related to MSC infusion, using toxicity scoring system
Incidence of severe adverse events (SAE)
Graft function after liver transplantation, measured in ALT, AST, GGT, bilirubin, albumin and INR |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Toxicity Score: day 2, 4, 7 and 10 after pediatric liver transplantation Monitoring of SAEs: continuosly Graft function: 360 and 720 days after liver transplantation |
|
E.5.2 | Secondary end point(s) |
Feasibility and safety of tapering immunosuppressive medication according to standard guidelines (Banff criteria, AASLD guidelines)
Time to first biopsy-proven acute rejection
Patient and graft survival |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Tapering Immunosuppression: 180, 270, 360, 450, 630 and 720 days after liver transplantation
Time to first biopsy-proven acute rejection: continously
Patient and graft survival: 360 and 720 days after liver 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 | 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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Donor-specific immune response of recipients
Recipient immunologic function in allograft tolerance |
|
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 | Yes |
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 | No |
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 | 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 | No |
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 | 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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |