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

• Status: Withdrawn
• Trial end date: 2022-10-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Methodist Hospital Research Institute; The Methodist Hospital System
• Collaborator: Veloxis Pharmaceuticals
• Treatments: Tacrolimus

Criteria

Inclusion Criteria:

• • Primary live donor or deceased donor renal allograft

• African American patients aged 18 to 65 years

• Ability to take oral medications

• Not currently on medications known to significantly interfere with tacrolimus metabolism, e.g. strong CYP3A4 inducers or inhibitors including but not limited to rifampin, rifabutin, phenytoin, carbamazepine, phenobarbital, protease inhibitors, azole antifungal (voriconazole, itraconazole, posaconazole, ketoconazole)

o Note: All patients will be discharged on clotrimazole 10 mg three times daily for one month for thrush prophylaxis, a known mild-to-moderate CYP3A4 inhibitor

• Female subjects of childbearing potential:

• Not current pregnant

• Agree not to try to become pregnant during the study period

• Agree to consistently use two forms of highly effective birth control throughout the study period

• Provision of signed and dated informed consent form

• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria:

• • Presence of a positive T- or B-cell flow cytometry allogeneic crossmatch

• Presence of pre-formed anti-human leukocyte antigen (HLA) donor-specific antibodies (DSAs)

• Recipient of an ABO-incompatible organ

• Receipt of a multi-organ or dual kidney transplant

• Receipt of pediatric en bloc deceased donor kidneys

• Receipt of deceased donor kidney with a kidney donor profile index (KDPI) greater than or equal to 85%

• Has undergone desensitization, or received antibody removal, anti-B-cell, or anti-plasma cell therapy in the 90 days preceding the transplant

• Planned initiation of antibody removal (i.e. plasmapheresis) within 7 days of the transplant procedure

• Positive test for latent tuberculosis (TB) and has not previously received adequate anti-microbial therapy or would require TB prophylaxis after transplant

• Uncontrolled concomitant infection that would not allow for targeting escalated tacrolimus trough concentrations, as deemed by prescriber

• Known infection or seropositivity for hepatitis B virus (HBV, defined by positive HBsAg, anti-HBcAg, or positive viral load) or hepatitis C virus (HCV) with active viral load

• Current malignancy

• Use of an investigational study in the 30 days prior to the transplant procedure