Envarsus on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation

Inclusion Criteria

• Kidney transplant patient ≥ 18 years and ≤ 80 years old
• Institutional Review Board (IRB) approved written Informed Consent and privacy language must be obtained from the subject or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
• Recipient of a de novo kidney from a living or deceased donor.

a. If deceased donor, a Kidney Donor Profile Index (KDPI) ≤ 85% are eligible for enrollment.

• Willingness to comply with study protocol.
• Previous kidney transplants will be permitted. Patients who are receiving a secondary transplant and who previously received Envarsus or who are currently on Envarsus as a component of maintenance immunosuppression and re-listed for transplant will be eligible to enroll in this study and will be randomized at the time of transplant to either cohort.
• Subject agrees not to participate in another study while on treatment.
• Female subject must be either:
• Of non-child-bearing potential,
• Post-menopausal (defined as at least 1 year without any menses) prior to screening, or
• Documented surgically sterile or status post-hysterectomy
• Or, if of childbearing potential,
• Agree not to try to become pregnant during the study and for 90 days after the final study drug administration
• And have a negative serum or urine pregnancy test within 7 days prior to transplant procedure
• And, if heterosexually active, agree to consistently use two forms of highly effective birth control (at least one of which must be a barrier method) which includes consistent and correct usage of established oral contraception, established intrauterine device or intrauterine system , or barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, starting at screening and throughout the study period and for 90 days after the final study drug administration.

Exclusion Criteria

• Patient is known to have a 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 or any unstable medical condition that could interfere with study objectives.
• Significant liver disease, defined as having, during the past 28 days, consistently elevated aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and/or alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SPGT)) levels greater than 3 times the upper value of the normal range of the investigational site.
• Patient who will be maintained on a non-tacrolimus-based maintenance immunosuppressive regimen following his/her transplant procedure.
• Patient currently taking, having taken within 30 days, or who will be maintained on an mechanistic target of rapamycin (mTOR) inhibitor following his/her transplant procedure.
• Use of an investigational study drug in the 30 days prior to the transplant procedure.
• Contraindication or hypersensitivity to drugs or any of their components that constitute the immunosuppression regimen.
• Known infection or seropositivity for HIV (HBsAg and Hepatitis C (HCV) positivity with negative viral load permitted).
• Focal segmental glomerulosclerosis.
• Subject has a current malignancy or history of malignancy (within the past 2 years), except non-metastatic basal or squamous cell carcinoma of the skin or carcinoma-in- situ of the cervix that has been successfully treated.
• Recipient of multi-organ kidney transplants.
• Recipient of an en bloc, adult or pediatric deceased donor kidney
• Any condition which, in the investigator's opinion, makes the subject unsuitable for study participation.