NCT04665310

Evaluation of Anti-rejection Drug, Tacrolimus, in African-Americans With Kidney Transplant

Evaluation of Early Dose Escalation Using Extended-Release Tacrolimus (Envarsus XR®) to Reduce Acute Rejection and Donor Specific Antibodies in African American Renal Transplant Recipients

• Status: Active Not Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: The Methodist Hospital Research Institute · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

In spite of conventional immunosuppression with lymphocyte-depleting induction followed by tacrolimus- and mycophenolate-based regimens, African American (AA) renal transplant recipients experience higher rates of acute rejection (AR), donor specific antibodies (DSA), and graft failure. Envarsus Extended-Release (XR)® (ENV) is a novel extended-release formulation of tacrolimus with a favorable pharmacokinetic profile, even in the setting of CYP3A5\*1 allele (rapid metabolizers). The investigator will evaluate the safety and efficacy of early dose escalation with ENV in AA recipients. The study hypothesis is that higher tacrolimus target concentrations may be achieved without typical dose-limiting toxicities, and this may ultimately result in lower incidence of early AR, DSA, and graft loss.

Detailed description

Phase 4 (post-marketing) De novo African American living or deceased donor renal transplant recipients 18 to 65 years of age Number of subjects to be enrolled: 60 All patients will receive standard induction immunosuppression according to institution protocol. Within one week of transplantation, all patients will be converted from immediate-release tacrolimus (TAC) to extended-release tacrolimus (ENV) at 20% reduction in total daily dosage. Patients will be randomized to low-, moderate-, or high-intensity ENV groups, stratified by peak panel reactive antibody (pPRA) greater than or equal to 75%. Target tacrolimus trough concentrations for the first month post-transplant will be 8-10 ng/mL in low-intensity group, 10-12 ng/mL in moderate-intensity group, and 12-14 ng/mL in high-intensity group; likewise from month 1-3 post-transplant, target trough concentrations will be 6-8 ng/mL, 8-10 ng/mL, and 10-12 ng/mL, respectively. Subjects experiencing dose-limiting adverse events (AEs) will be de-escalated as warranted. Following month 3, all patients will be maintained on ENV at target tacrolimus trough concentrations according to institution protocol. Additional maintenance immunosuppression will consist of mycophenolate mofetil (MMF) at a goal dose of 2000 mg daily along with an oral prednisone taper to 5-10 mg daily by the end of month 1. All patients will be followed for 6 months post-transplant.

Conditions

• Kidney Disease, End-Stage
• Donor Specific Antibodies
• Acute Rejection of Renal Transplant

Interventions

Type	Name	Description
DRUG	Envarsus XR	tacrolimus, extended-release tablets, a calcineurin inhibitor

Timeline

• Start date: 2018-09-01
• Primary completion: 2025-07-31
• Completion: 2025-10-31
• First posted: 2020-12-11
• Last updated: 2025-03-14

Regulatory

• FDA-regulated drug study