E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
liver and kidney transplantation |
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E.1.1.1 | Medical condition in easily understood language |
liver and kidney transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
To determine the pharmacokinetics of tacrolimus following oral administration of Modigraf, after the first oral dose and at steady state in pediatric participants undergoing de novo allograft liver or kidney transplantation. |
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E.2.2 | Secondary objectives of the trial |
To observe the safety and efficacy of Modigraf in de novo pediatric allograft liver and kidney transplantation recipients. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Participants are eligible for the study if all of the following apply: 1. Male or female participants are eligible for the study if they are aged < 18 years undergoing de novo liver or kidney allograft transplantation. 2. Participant’s parent(s) or their legal representative(s) has been fully informed and has given written informed consent to participate in the study. Participant has given assent where applicable. 3. Participant’s parent(s) or their legal representative(s), and participant where applicable agrees not to participate in another interventional study while participating in the present study from 1 month before screening to the end of the study. |
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E.4 | Principal exclusion criteria |
Participants will be excluded from participation if any of the following apply: 1. Participant has previously received another organ transplant. 2. Participant has a high immunological risk, defined as a panel reactive antibody (PRA) score > 50% in the previous 6 months (only applicable for kidney transplantation recipients). 3. Cold ischemia time of the donor kidney longer than 30 hours (only applicable for kidney transplantation recipients). 4. Bilateral kidney transplantation recipients (only applicable for kidney transplantation recipients). 5. Participant receives an ABO incompatible donor organ. 6. Participant has significant kidney impairment, defined as having serum creatinine ≥ 230 μmol/L (≥ 2.6 mg/dL) prior to transplantation (not applicable for kidney transplantation recipients). 7. Participant has significant liver disease, defined as having elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) and/or total bilirubin (TBL) levels 3 times the upper value of the normal range prior to transplantation (not applicable for liver transplantation recipients). 8. Participants with malignancies or a history of malignancy within the last 5 years. 9. Participant 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. Recipient or donor known to be human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) positive. 11. Participant requires systemic immunosuppressive medication for any indication other than transplantation. 12. Participants taking or requiring to be treated with medication or substances prohibited by this protocol, such as herbal remedies. 13. Known allergy or intolerance to steroids, macrolide antibiotics, basiliximab, or tacrolimus. 14. Participants with very low body weight or severe primary disease/complications which are judged by investigators to be unsuitable for participating in this study. 15. Participant is currently participating in another clinical trial and/or has been taking any other study drug within 1 month prior to screening. 16. Participant is unlikely to comply with the visits scheduled in the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The following pharmacokinetic parameters for tacrolimus will be determined after the morning dose on day 1 and day 7 (+7 days): • AUCtau • Cmax • tmax • Ctrough • The correlation between Ctrough and AUCtau
The efficacy of Modigraf will be described from the following parameters within 12 months: • Rejection episodes within 12 months • Participant and graft survival within 12 months
The safety of Modigraf will be described from the following parameters within 12 months: • Number of dose changes throughout the study period • Incidence of AEs within 12 months • Laboratory parameters throughout the study period • Vital signs throughout the study period • Physical examination throughout the study period • Electrocardiograph (ECG) throughout the study period • Tacrolimus whole blood trough levels within 12 months |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1 and Day 7 and up to 12 months following Modigraf administration |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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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.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |