E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
De novo allograft transplantation (liver, heart, kidney) in paediatric patients. |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of rejection by the body of newly transplanted liver, heart and kidney transplants in children. |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019314 |
E.1.2 | Term | Heart transplant |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023438 |
E.1.2 | Term | Kidney transplant |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024716 |
E.1.2 | Term | Liver transplantation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
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 determine the pharmacokinetics (PK) of tacrolimus following oral administration of
Modigraf®, after the first oral dose and at steady state in paediatric subjects undergoing de novo allograft transplantation. |
|
E.2.2 | Secondary objectives of the trial |
Safety and efficacy of Modigraf®. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is 12 years of age or younger.
2. The subject is the recipient of a solid organ (liver, kidney or heart) transplant. Multiorgan transplants are acceptable as long as one of the organs transplanted is liver, kidney or heart.
3. The subject’s parent(s) or their legal representative(s) has been fully informed and has given written informed consent to participate in the study. The subject has given assent where applicable. |
|
E.4 | Principal exclusion criteria |
1. The subject has previously received another organ transplant (including liver, kidney or heart re-transplantation).
2. Subject has a high immunological risk, defined as a Panel Reactive Antibody (PRA)
score >50% in the previous 6 months (only applicable for renal transplant recipients).
3. Cold ischemia time of the donor kidney greater than 30 hours (only applicable for renal transplant recipients).
4. Subject receives an AB0 incompatible donor organ.
5. Subject has significant renal impairment, defined as having serum creatinine ≥230
μmol/l (≥2.6 mg/dl) pre-transplantation (not applicable for renal transplant recipients).
6. Subject has significant liver disease, defined as having elevated ALT and/or AST and/or Total Bilirubin levels 3 times the upper value of the normal range during the 28 days prior to transplantation (not applicable for liver transplant recipients).
7. Subject with pulmonary vascular resistance greater than 4 Wood units which is
unresponsive to treatment.
8. Subjects with malignancies or a history of malignancy within the last 5 years.
9. Subject has a significant, uncontrolled systemic infection and/or severe diarrhea,
vomiting, active upper gastrointestinal disorder that may affect the absorption of
tacrolimus or has an active peptic ulcer.
10. Subject requires systemic immunosuppressive medication for any indication other than transplantation.
11. Recipient or donor known to be HIV, HCV or HBV positive.
12. Known allergy or intolerance to steroids, macrolide antibiotics, basiliximab or tacrolimus.
13. Subject is currently participating in another clinical trial and/or has been taking an
investigational drug in the 3 months prior to transplantation.
14. Subject is unlikely to comply with the visits scheduled in the protocol.
15. Subjects taking or requiring to be treated with medication or substances prohibited by this protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PK parameters for tacrolimus will be determined after the morning dose on
Day 1 and Day 7 (+7 days):
- AUCtau
- Cmax
- tmax
- Ctrough |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Efficacy:
• Rejection episodes
• Patient and graft survival
Safety:
• Incidence of adverse events
• Laboratory parameters
• Vital signs |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 14 (end of study duration) |
|
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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | Information not present in EudraCT |
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
| 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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | Information not present in EudraCT |
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 last patient. |
|
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 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |