Clinical trial NCT05152628: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Liver Transplantation
Kidney Transplantation
Keywords: Liver Transplantation
Kidney Transplantation
Modigraf
Tacrolimus
Pediatric
Pharmacokinetics
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2021-12-10
Enrollment: 55
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetics (PK) of tacrolimus granules in whole blood: area under the blood concentration - time curve for a dosing interval (AUCtau) on Day 1
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
measure: PK of tacrolimus granules in whole blood: AUCtau on Day 7
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
measure: PK of tacrolimus granules in whole blood: maximum concentration (Cmax) on Day 1
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
measure: PK of tacrolimus granules in whole blood: Cmax on Day 7
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
measure: PK of tacrolimus granules in Whole Blood: Time of Maximum Concentration (Tmax) on Day 1
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
measure: PK of tacrolimus granules in Whole Blood: Tmax on Day 7
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
measure: PK of tacrolimus granules in whole blood: Trough blood concentration (Ctrough) on Day 1
timeFrame: Pre-dose on day 1
measure: PK of granules tacrolimus in whole blood: Ctrough on Day 7
timeFrame: Pre-dose on day 7
measure: Correlation between Ctrough and AUCtau of tacrolimus granules PK parameters in whole blood on Day 1
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
measure: Percentage of Participants With Acute Rejection (AR)
timeFrame: From first dose to month 12
measure: Number of Participants who Died
timeFrame: From first dose to month 12
measure: Number of Participants with Graft Failure
timeFrame: From first dose to month 12
measure: Number of Dose Adjustments Throughout the Study Period
timeFrame: From first dose to month 12
measure: Number of Participants with Treatment Emergent Adverse Events (AEs)
timeFrame: From first dose to month 12
measure: Whole Blood Trough Levels of Tacrolimus
timeFrame: From day 1 through month 12 (predose)
measure: Correlation between Ctrough and AUCtau of tacrolimus granules in whole blood on Day 7
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
measure: PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 1
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
measure: PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 7
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
measure: PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 1
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
measure: PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 7
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
measure: PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 1
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 1
measure: PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 7
timeFrame: Predose, 0.5, 1, 2, 8, 12 hours post dose on day 7
measure: Percentage of Participants With Biopsy-Proven Acute Rejections (BPAR)
timeFrame: From first dose to month 12
measure: Percentage of Participants With Clinically Suspected Rejection
timeFrame: From first dose to month 12
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Site CN86003
city: Guangzhou
country: China
facility: Site CN86002
city: Shanghai
country: China
facility: Site CN86001
city: Wuhan
country: China
facility: Site CN86004
Study officials:
affiliation: Astellas Pharma China, Inc.
name: Manager Medical Science
role: STUDY_DIRECTOR
References: