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

Despite lower rates of acute rejection and short-term improvements in patient and graft
survival, the rate of late allograft loss following kidney transplantation has remained
unchanged. Achievement of therapeutic, minimally toxic, tacrolimus concentrations early
(within 30 days), after transplantation, is known to be important since achieving it has been
associated with a lowered risk of acute rejection. The investigators hypothesize that using
extended release tacrolimus (Envarsus XR, Veloxis), will provide more stable, more effective,
and less toxic levels of tacrolimus in renal allograft recipients. Therefore, the
investigators propose to analyze the impact of the blood concentration normalized by the dose
(C/D ratio) on kidney function after renal transplantation in experimental group that will be
treated with Envarsus XR and the standard of care (SOC) group treated with twice a day
tacrolimus.

Inclusion Criteria:

1. Kidney transplant patient ≥ 18 years and ≤ 80 years old

2. 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).

3. 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.

4. Willingness to comply with study protocol.

5. 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.

6. Subject agrees not to participate in another study while on treatment.

7. Female subject must be either:

1. 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

2. 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:

1. 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.

2. Uncontrolled concomitant infection or any unstable medical condition that could
interfere with study objectives.

3. 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.

4. Patient who will be maintained on a non-tacrolimus-based maintenance immunosuppressive
regimen following his/her transplant procedure.

5. 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.

6. Use of an investigational study drug in the 30 days prior to the transplant procedure.

7. Contraindication or hypersensitivity to drugs or any of their components that
constitute the immunosuppression regimen.

8. Known infection or seropositivity for HIV (HBsAg and Hepatitis C (HCV) positivity with
negative viral load permitted).

9. Focal segmental glomerulosclerosis.

10. 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.

11. Recipient of multi-organ kidney transplants.

12. Recipient of an en bloc, adult or pediatric deceased donor kidney

13. Any condition which, in the investigator's opinion, makes the subject unsuitable for
study participation.