A Study to Evaluate the Safety and Efficacy of a Modigraf® Based Immunosuppression Regimen in De Novo Pediatric Allograft Liver and Kidney Transplantation Recipients

Phase 4

Completed

• Conditions: Liver Transplantation; Kidney Transplantation
• Interventions: Drug: Tacrolimus granules

• Registration Number: NCT05153915
• Lead Sponsor: Astellas Pharma China, Inc.

Brief Summary

The purpose of this study is to observe the safety and efficacy of Modigraf in de novo pediatric allograft liver and kidney transplantation recipients. This study will also monitor dose changes and tacrolimus whole blood trough levels of Modigraf based immunosuppression regimen.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-30
• Study First Submitted QC: 2021-11-30
• Study First Posted: 2021-12-10
• Study Start: 2021-12-30
• Primary Completion: 2024-03-14
• Study Completion: 2024-03-14
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• 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.

Exclusion Criteria

• Participant has previously received another organ transplant.
• 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).
• Cold ischemia time of the donor kidney longer than 30 hours (only applicable for kidney transplantation recipients).
• Bilateral kidney transplantation recipients (only applicable for kidney transplantation recipients).
• Participant receives an ABO incompatible donor organ.
• 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).
• 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).
• Participants with malignancies or a history of malignancy within the last 5 years.
• 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.
• Recipient or donor known to be human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV) positive.
• Participant requires systemic immunosuppressive medication for any indication other than transplantation.
• Participants taking or requiring to be treated with medication or substances prohibited by this protocol.
• Known allergy or intolerance to steroids, macrolide antibiotics, basiliximab, or tacrolimus.
• Participants with severe primary disease/complications/poor general condition which may be unsuitable for participating in this study.
• Participant is currently participating in another clinical trial and/or has been taking any other study drug within 1 month prior to screening.
• Participant is unlikely to comply with the visits scheduled in the protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Liver Transplant	Tacrolimus granules	Pediatric participants who undergo de novo allograft liver transplantation receive initial daily dose of 0.15 to 0.3 milligram per kilogram (mg/kg) of body weight oral suspension of tacrolimus granules post-operatively for 12 months.
Kidney Transplant	Tacrolimus granules	Pediatric participants who undergo de novo allograft kidney transplantation receive initial daily dose of 0.15 to 0.3 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants with Biopsy-Proven Acute Rejections (BPAR)	From first dose to month 12	AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection was performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies". A BPAR episode was defined as any AR episode confirmed by biopsy.
Percentage of Participants with clinically suspected Rejection	From first dose to month 12	AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection was performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies". An AR was clinically suspected in participants who experienced an increase in serum creatinine, after the exclusion of other causes of graft dysfunction (generally with biopsy).
Number of participants with graft failure	From first dose to month 12	Graft failure is defined as graft dysfunction including re-transplantation, graft loss or death, during the study period. A graft dysfunction to permanent dialysis in kidney transplantation was also considered as graft failure.
Percentage of Participants With Acute Rejection (AR)	From first dose to month 12	AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection was performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies".
Number of Participants who Died	From first dose to month 12	Number of participants who died is recorded during 12 months' post-transplant; any cause of death was taken into account.
Number of dose adjustments throughout the study period	From first dose to month 12	The number of dose changes will The dose adjustments required for the organ transplant were reported. The Safety Analysis Set (SAF) consisted of all participants who took at least one dose of study drug.
Number of participants with Treatment Emergent adverse events (AEs)	From first dose to month 12	An AE is defined as any untoward medical occurrence in a participant administered a study drug not necessarily linked to this treatment. An AE can be any unfavorable and unintended sign (e.g., abnormal laboratory finding; abnormal laboratory test result or other safety assessment, symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. Treatment emergent adverse event (TEAE) is defined as AE observed after administering the study drug.
Whole Blood Trough Levels of Tacrolimus	From month 1 through month 12 (predose)	Tacrolimus whole blood trough levels are routinely monitored from whole blood samples, using a local assay method, for example EMITÒ or Liquid-Chromatography-Mass-Spectrometry-Mass-Spectrometry (LC-MS-MS) in the local laboratories.

Trial Locations

Locations (7)

Site CN86001; 🇨🇳 Guangzhou, China

Site CN86003; 🇨🇳 Beijing, China

Site CN86006; 🇨🇳 Changsha, China

Site CN86004; 🇨🇳 Wuhan, China

Site CN86002; 🇨🇳 Shanghai, China

Site CN86005; 🇨🇳 Zhengzhou, China

Site CN86007; 🇨🇳 Tianjin, China