Clinical Outcome of Delayed or Standard Prograf Together With Induction Therapy Followed by Conversion to Advagraf in Donation After Cardiac (or Circulatory) Death (DCD) Kidney Transplant Recipients

• ClinicalTrials.gov Identifier: NCT03644485
• Recruitment Status: Active, not recruiting
• First Posted: August 23, 2018
• Last Update Posted: February 17, 2022
• Sponsor: Astellas Pharma China, Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma China, Inc. )

Study Description

Brief Summary:

The purpose of this study is to confirm non-inferiority of delayed Prograf treatment to standard Prograf treatment in the incidence of delayed graft function (DGF) within 1 week between the 2 immunosuppressive (IS) treatment groups: delayed or standard Prograf together with induction therapy, and then convert to Advagraf usage in donation after cardiac (or circulatory) death (DCD) kidney transplant recipients.

This study will also compare the clinical outcome within 6 month post-transplant between the 2 IS treatment groups and compare the safety throughout study period between the 2 IS treatment groups.

Condition or disease	Intervention/treatment	Phase
Kidney Transplant	Drug: Tacrolimus immediate-release formulation; Drug: Tacrolimus prolonged-release formulation; Drug: Induction therapy; Drug: Mycophenolic acid drugs; Drug: Corticosteroids	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 284 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Outcome of Delayed or Standard Prograf Together With Induction Therapy Followed by Conversion to Advagraf in Donation After Cardiac (or Circulatory) Death (DCD) Kidney Transplant Recipients: A Randomized, Open-label, Multicenter Clinical Trial
• Actual Study Start Date: October 22, 2018
• Actual Primary Completion Date: January 6, 2022
• Estimated Study Completion Date: July 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Standard Prograf group; Participants will receive induction therapy, tacrolimus immediate-release formulation (Prograf) from Day 1 after kidney transplant surgery to Month 1 and convert to tacrolimus prolonged-release formulation (Advagraf) up to Month 6.	Drug: Tacrolimus immediate-release formulation; oral; Other Names: Prograf; FK506; Drug: Tacrolimus prolonged-release formulation; oral; Other Names: Advagraf; FK506; Drug: Induction therapy; All participants will receive induction therapy. The dosage and administration of induction immunotherapy will be a single kind of drug determined by the investigator.; Drug: Mycophenolic acid drugs; All participants will receive mycophenolic acid drugs in combination with corticosteroids. The dosage and administration of mycophenolic acid will be determined by the investigator.; Drug: Corticosteroids; All participants will receive corticosteroids in combination with mycophenolic acid drugs. The dosage and administration of corticosteroids will be determined by the investigator.
Experimental: Delayed Prograf group; Participants will receive induction therapy, tacrolimus immediate-release formulation (Prograf) from Day 3 - 5 after kidney transplant surgery to Month 1 and convert to tacrolimus prolonged-release formulation (Advagraf) up to Month 6.	Drug: Tacrolimus immediate-release formulation; oral; Other Names: Prograf; FK506; Drug: Tacrolimus prolonged-release formulation; oral; Other Names: Advagraf; FK506; Drug: Induction therapy; All participants will receive induction therapy. The dosage and administration of induction immunotherapy will be a single kind of drug determined by the investigator.; Drug: Mycophenolic acid drugs; All participants will receive mycophenolic acid drugs in combination with corticosteroids. The dosage and administration of mycophenolic acid will be determined by the investigator.; Drug: Corticosteroids; All participants will receive corticosteroids in combination with mycophenolic acid drugs. The dosage and administration of corticosteroids will be determined by the investigator.

Outcome Measures

Primary Outcome Measures :

1. Incidence of delayed graft function (DGF) [ Time Frame: Up to Day 7 after transplantation ]
   DGF is defined as dialysis requirement during the first post-transplant week (7 days).

Secondary Outcome Measures :

1. Incidence of acute rejection (AR) [ Time Frame: Up to Month 6 after transplantation ]
   The reporting of AR includes any biopsy-proven or clinically-suspected rejection of a subject after transplantation.
2. Renal function assessed by estimated glomerular filtration rate (eGFR) [ Time Frame: Up to Month 6 after transplantation ]
   eGFR will be derived using the abbreviated Modification of Diet in Renal Disease (MDRD) formula.
3. Renal function assessed by serum creatinine [ Time Frame: Up to Month 6 after transplantation ]
   Serum creatinine will be measured from serum sample collected.
4. Renal function assessed by urea nitrogen [ Time Frame: Up to Month 6 after transplantation ]
   Urea nitrogen will be measured from serum sample collected.
5. Subject survival [ Time Frame: Up to Month 6 after transplantation ]
   Subject survival is the time from the date of transplantation to the date of death or the date of the last follow-up. Subject survival will be estimated using Kaplan Meier estimates and compared by log rank test.
6. Graft survival [ Time Frame: Up to Month 6 after transplantation ]
   Graft survival is an estimate of the probability of the transplant functioning at a finite time after transplantation. Graft survival will be calculated from the date of transplantation to the date of irreversible graft failure or the date of the last follow-up during the period when the transplant is still functioning or to the date of death.
7. Safety assessed by incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Up to Month 7 after transplantation ]
   Adverse events (AEs) will be coded using the latest version of MedDRA. TEAE is defined as any AE following the transplantation until the end of the study.
8. Safety assessed by incidence of serious adverse events (SAEs) [ Time Frame: Up to Month 7 after transplantation ]
   AE is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.
9. Number of participants with laboratory test abnormalities and/or AEs [ Time Frame: Up to Month 7 after transplantation ]
   Number of participants with potentially clinically significant laboratory values.
10. Number of participants with vital sign abnormalities and/or AEs [ Time Frame: Up to Month 7 after transplantation ]
    Number of participants with potentially clinically significant vital sign values.
11. Number of participants with 12-lead electrocardiograms (ECG) abnormalities and/or AEs [ Time Frame: Up to Month 7 after transplantation ]
    ECG will be performed in the supine position after the subject has been breathing quietly for 5 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subject has end-stage kidney disease who is a suitable candidate for primary DCD kidney transplantation.
• Subject is a resident of China.
• Subject is scheduled to undergo DCD renal allograft transplantation with compatible ABO blood type.
• Subject has peak panel-reactive antibodies (PRA) < 10% or "Negative" test result.
• Subject must be a recipient of a DCD kidney and receive the organ distributed by China Organ Transplant Response System only.

• Female subject must either:

  • Be of non-childbearing potential: Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or documented surgically sterile
  • Or, if of childbearing potential: Agree not to try to become pregnant throughout the study period and have a negative blood pregnancy test at screening.
• A sexually active male or female subject is utilizing highly effective forms of birth control starting at screening and throughout the study period if the risk of conception exists.
• Subject agrees not to participate in another interventional study while participating in the present study from 1 month before randomization to 1 month after the last dose of investigational drug.

Exclusion Criteria:

• Subject has previously received or is receiving an organ transplant other than kidney.
• Subject is receiving double-kidney transplant.
• Recipients of Maastricht Class I, II, and V donor organs.
• Recipients of Maastricht Class III and IV donor organs without a full complement of intensive care unit and intraoperative records.
• Subject has cold ischemia time of allograft > 24 hours before kidney transplantation surgery.
• Subject has known contraindication to administration of tacrolimus (Prograf or Advagraf), or other macrolides.
• Subject is unlikely to comply with the visits scheduled in the protocol or has a history of non-compliance.
• Subject has evidence of active liver disease or the presence of a chronic active hepatitis B or C within 1 month prior to kidney transplant surgery.
• Recipient or donor is seropositive for human immunodeficiency virus.
• Subject has active systemic infection requiring the use of antimicrobial agents within 1 week prior to kidney transplant surgery.
• Subject has current malignancy or a history of malignancy (within the past 5 years), except non- metastatic basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully.
• Subject has medical or psychological conditions which would preclude compliance with the study requirements.
• Subject has any condition, including any uncontrolled disease state other than end-stage kidney disease, that constitutes an inappropriate risk or a contraindication for participation in the study, or that could interfere with the study objectives, conduction, or evaluation.
• Female subject who breastfeed or donate ova starting at screening and throughout the study period.
• Male subject who donate sperm starting at screening and throughout the study period.

Contacts and Locations

Locations

China

Site CN08608

Beijing, China

Site CN08619

Beijing, China

Site CN08609

Changsha, China

Site CN08604

Guangzhou, China

Site CN08614

Hangzhou, China

Site CN08617

Hangzhou, China

Site CN08610

Nanjing, China

Site CN08618

Nanjing, China

Site CN08612

Shanghai, China

Site CN08603

Tianjin, China

Site CN08621

Wenzhou, China

Site CN08602

Wuhan, China

Site CN08613

Wuhan, China

Site CN08620

Wuhan, China

Site CN08605

Xi'an, China

Sponsors and Collaborators

Astellas Pharma China, Inc.

Investigators

• Study Director: Medical Director; Astellas Pharma China, Inc.

More Information

• Responsible Party: Astellas Pharma China, Inc.
• ClinicalTrials.gov Identifier: NCT03644485
• Other Study ID Numbers: 506-MA-3186
• First Posted: August 23, 2018
• Last Update Posted: February 17, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on https://www.clinicalstudydatarequest.com/
• 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.
• 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.
• URL: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma China, Inc. ):

kidney transplant; Tacrolimus; Prograf; Advagraf; FK506

Additional relevant MeSH terms:

Mycophenolic Acid; Tacrolimus; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Calcineurin Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antibiotics, Antineoplastic; Antineoplastic Agents; Antibiotics, Antitubercular; Antitubercular Agents; Anti-Bacterial Agents; Anti-Infective Agents