A Study of Modigraf® (Tacrolimus Granules) to Evaluate the Pharmacokinetics and Long-term Safety and Efficacy in De Novo Pediatric Allograft Liver and Kidney Transplantation Recipients

A Multicenter, Open-label, Non-comparative Study of Modigraf® (Tacrolimus Granules) to Evaluate the Pharmacokinetics and Long-term Safety and Efficacy in De Novo Pediatric Allograft Liver and Kidney Transplantation Recipients

The purpose of this study is 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. This study will also observe the safety and efficacy of Modigraf in de novo pediatric allograft liver and kidney transplantation recipients.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Kidney Transplantation
• Intervention / Treatment: Drug: Tacrolimus granules

Detailed Description

Pediatric participants will be treated with a Modigraf (tacrolimus granules) based immunosuppressive regimen for 12 months.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Astellas Pharma China, Inc.; Phone Number: +86-010-85216332/3; Email: astellas.registration@astellas.com

Study Locations

• China
  • Beijing, China
    • Site CN86003
  • Guangzhou, China
    • Site CN86002
  • Shanghai, China
    • Site CN86001
  • Wuhan, China
    • Site CN86004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tacrolimus granules (Modigraf); Participants will receive the first dose of Modigraf in the morning within 24 hours after reperfusion. Total initial dose will be received in two divided doses post operatively. Subsequent oral Modigraf doses will be adjusted by the investigator and will be received in two doses (recommended interval 12 hours)	Drug: Tacrolimus granules; Oral; Other Names: Modigraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of tacrolimus in whole blood: area under the blood concentration - time curve for a dosing interval (AUCtau)	AUCtau will be recorded from the pharmacokinetic (PK) whole blood sample collected.	Up to 14 days
Pharmacokinetics of tacrolimus in whole blood: maximum concentration (Cmax)	Cmax will be recorded from the PK whole blood sample collected.	Up to 14 days
Pharmacokinetics of tacrolimus in whole blood: time to attain Cmax (tmax)	tmax will be recorded from the PK whole blood sample collected.	Up to 14 days
Pharmacokinetics of tacrolimus in whole blood: blood concenration at the end of a dosing interval (Ctrough)	Ctrough will be recorded from the PK whole blood sample collected.	Up to 14 days
Determine the correlation between Ctrough and AUCtau PK parameters	The correlation between Ctrough and AUCtau PK parameters will be assessed by Pearson's coefficient at each sample time.	up to 14 days
Incidence of rejection episodes	The reporting of acute rejection includes any biopsy-proven or clinically suspected rejection of a participant after transplantation.	Up to 12 months
Number of participant survivals	Participant survival status will be recorded during 12 months post-transplant.	Up to 12 months
Number of graft survivals	Graft failure is defined as graft dysfunction, including re-transplantation or death.	Up to 12 months
Number of dose changes throughout the study period	The number of dose changes will be recorded throughout the study period.	Up to 12 months
Number of participants with Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not related to study drug.	Up to 12 months
Number of participants with laboratory value abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant laboratory values.	Up to 12 months
Number of participants with vital sign abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant vital sign values.	Up to 12 months
Number of participants with electrocardiogram (ECG) abnormalities and/or adverse events (AE)	Number of participants with potentially clinically significant ECG values.	Up to 12 months
Assess levels of Tacrolimus whole blood trough using a local assay method	Tacrolimus whole blood trough levels will be routinely monitored using a local assay method, for example EMITÒ or Liquid-Chromatography-Mass-Spectrometry-Mass-Spectrometry (LC-MS-MS) in local laboratories.	Up to 12 months

Collaborators and Investigators

• Sponsor: Astellas Pharma China, Inc.
• Investigators: Study Director: Manager Medical Science, Astellas Pharma China, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2022
• Primary Completion (Actual): March 6, 2024
• Study Completion (Actual): March 6, 2024

Study Registration Dates

• First Submitted: November 29, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Pediatric; Pharmacokinetics; Tacrolimus; Kidney Transplantation; Liver Transplantation; Modigraf
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: F506-CL-0405; CTR20212678 (Registry Identifier: ChinaDrugTrials.org.cn)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No