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

March 13, 2025 updated by: Astellas Pharma China, Inc.

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Liver Transplant
Pediatric participants who undergo de novo allograft liver transplantation receive initial daily dose of 0.2 milligram per kilogram (mg/kg) of body weight oral suspension of tacrolimus granules post-operatively for 12 months.
Drug: Tacrolimus granules
Oral
Other Names:
  • Modigraf
Experimental: Kidney Transplant
Pediatric participants who undergo de novo allograft kidney transplantation receive initial daily dose of 0.2 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.
Drug: Tacrolimus granules
Oral
Other Names:
  • Modigraf

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
PK of tacrolimus granules in whole blood: Trough blood concentration (Ctrough) on Day 1
Time Frame: Pre-dose on day 1
Ctrough is recorded from the PK blood samples collected.
Pre-dose on day 1
PK of granules tacrolimus in whole blood: Ctrough on Day 7
Time Frame: Pre-dose on day 7
Ctrough is recorded from the PK blood samples collected.
Pre-dose on day 7
Percentage of Participants With Acute Rejection (AR)
Time Frame: 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 is performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies".
From first dose to month 12
Number of Participants who Died
Time Frame: From first dose to month 12
Number of participant who died is recorded during 12 months' post-transplant; any cause of death is taken into account.
From first dose to month 12
Number of Participants with Graft Failure
Time Frame: From first dose to month 12
Graft failure is defined as graft dysfunction, including re-transplantation or death, during the study period. A graft dysfunction to permanent dialysis in kidney transplantation is also considered as graft failure.
From first dose to month 12
Number of Dose Adjustments Throughout the Study Period
Time Frame: From first dose to month 12
The dose adjustments required for the organ transplant is reported.
From first dose to month 12
Number of Participants with Treatment Emergent Adverse Events (AEs)
Time Frame: From first dose to month 12
An AE is defined as any untoward medical occurrence in a participant given 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 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.
From first dose to month 12
Whole Blood Trough Levels of Tacrolimus
Time Frame: From day 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. Mean trough levels of tacrolimus from day 1 through month 12 are reported.
From day 1 through month 12 (predose)
Percentage of Participants With Biopsy-Proven Acute Rejections (BPAR)
Time Frame: 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 is 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 is defined as any AR episode confirmed by biopsy.
From first dose to month 12
Percentage of Participants With Clinically Suspected Rejection
Time Frame: 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 is performed by the local histopathologist following the "Histological Grading of Liver Biopsies for Rejection", the "Banff diagnostic categories for renal allograft biopsies". An AR is clinically suspected in participants who experienced an increase in serum creatinine, after the exclusion of other causes of graft dysfunction (generally with biopsy).
From first dose to month 12
Pharmacokinetics (PK) of tacrolimus granules in whole blood: area under the blood concentration - time curve for a dosing interval (AUCtau) on Day 1
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
AUCtau is recorded from the pharmacokinetic (PK) whole blood samples collected.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
PK of tacrolimus granules in whole blood: AUCtau on Day 7
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
AUCtau is recorded from the PK blood samples collected.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
PK of tacrolimus granules in whole blood: maximum concentration (Cmax) on Day 1
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Cmax is recorded from the PK blood samples collected. Cmax is maximum concentration observed in an observation period.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
PK of tacrolimus granules in whole blood: Cmax on Day 7
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Cmax is recorded from the PK blood samples collected. Cmax is maximum concentration observed in an observation period.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
PK of tacrolimus granules in Whole Blood: Time of Maximum Concentration (Tmax) on Day 1
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Tmax is recorded from the PK blood samples collected. Tmax is time of maximum concentration in an observation period.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
PK of tacrolimus granules in Whole Blood: Tmax on Day 7
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Tmax is recorded from the PK blood samples collected. Tmax is time of maximum concentration in an observation period.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Correlation between Ctrough and AUCtau of tacrolimus granules PK parameters in whole blood on Day 1
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
The correlation between Ctrough and AUCtau PK parameters will be assessed by Pearson's coefficient at each sample time by visit.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Correlation between Ctrough and AUCtau of tacrolimus granules in whole blood on Day 7
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
The correlation between Ctrough and AUCtau is assessed by Pearson's coefficient at each sample time by visit.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 1
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Dose-normalized AUCtau is AUCtau normalized with the dose just prior to blood sampling. Dose-normalized AUCtau is calculated as AUCtau/dose.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 7
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Dose-normalized AUCtau is AUCtau normalized with the dose just prior to blood sampling. Dose-normalized AUCtau is calculated as AUCtau/dose.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 1
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Dose-normalized Cmax is Cmax normalized with the dose just prior to blood sampling. Dose-normalized Cmax is calculated as Cmax/dose.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 7
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Dose-normalized Cmax is Cmax normalized with the dose just prior to blood sampling. Dose-normalized Cmax is calculated as Cmax/dose.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 1
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
Ctrough normalized with the dose just prior to blood sampling. Dose-normalized Ctrough is calculated as Ctrough/dose.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 7
Time Frame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
Ctrough normalized with the dose just prior to blood sampling. Dose-normalized Ctrough is calculated as Ctrough/dose.
Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Astellas Pharma China, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Manager Medical Science, Astellas Pharma China, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 11, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 6, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 6, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 29, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 10, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • F506-CL-0405
  • CTR20212678 (Registry Identifier: ChinaDrugTrials.org.cn)
  • 2022-002350-68 (Registry Identifier: EudraCT)

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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings