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

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05152628
• Other study ID #: F506-CL-0405
• Secondary ID: CTR20212678
• Status: Completed
• Phase: Phase 4
• Start date: January 11, 2022
• Est. completion date: March 6, 2024

Study information

• Verified date: March 2024
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: March 6, 2024
• Est. primary completion date: March 6, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Transplantation
• Liver Transplantation

Intervention

Drug:
• Tacrolimus granules
Oral

Locations

Country	Name	City	State
China	Site CN86003	Beijing
China	Site CN86002	Guangzhou
China	Site CN86001	Shanghai
China	Site CN86004	Wuhan

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma China, Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Pharmacokinetics of tacrolimus in whole blood: maximum concentration (Cmax)	Cmax will be recorded from the PK whole blood sample collected.	Up to 14 days
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Number of participant survivals	Participant survival status will be recorded during 12 months post-transplant.	Up to 12 months
Primary	Number of graft survivals	Graft failure is defined as graft dysfunction, including re-transplantation or death.	Up to 12 months
Primary	Number of dose changes throughout the study period	The number of dose changes will be recorded throughout the study period.	Up to 12 months
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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