Clinical trial NCT03511560: Envarsus on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation
Official title: To Understand the Impact of Immunosuppression Using Once-per-day Envarsus XR on the Effect of Total Tacrolimus Dose/Trough Level Ratio on Renal Function (eGFR) in Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplant Rejection
Kidney Transplant Failure and Rejection
Keywords: Envarsus XR
Tacrolimus
Kidney Transplantation
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Veloxis Pharmaceuticals
First posted: 2018-04-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, Envarsus vs Prograf
Primary purpose: PREVENTION

Brief summary: This is a one year, prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, extended-release Tacrolimus (Envarsus XR) versus twice daily Tacrolimus (Prograf). It will examine kidney function between the two groups using estimated glomerular filtration rate (eGFR) and also examine one-year kidney outcomes, including graft loss and patient death. Patients will be followed for up to 1 year during the open-label study period.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean C/D Ratio
timeFrame: Every Month for up to 1 year
Secondary outcomes:
measure: Mean Serum Creatinine Level
timeFrame: 12 months
measure: Patient Survival Rate
timeFrame: 12 months
measure: Graft Survival Rate
timeFrame: 12 months
measure: Number of Rejection Episodes
timeFrame: 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Mark Hardy, MD
role: PRINCIPAL_INVESTIGATOR
References: