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

NCT03511560 | Completed Phase 4 Results FDA Drug

• 1 other identifier: AAAR6805
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Transplant Rejection; Kidney Transplant Failure and Rejection

Keywords

Envarsus XR; Tacrolimus; Kidney Transplantation

Outcome Measures

Primary Outcomes (1)

• Mean C/D Ratio

  Tacrolimus metabolism was determined for all dates of tacrolimus blood trough concentration collection after renal transplantation by dividing the tacrolimus blood trough concentration (C) by the corresponding total daily tacrolimus dose (D). C/D ratio (ng/mL\*1/mg) = blood tacrolimus trough level (ng/mL)/total daily tacrolimus dose (mg).

  Every Month for up to 1 year

Secondary Outcomes (4)

• Mean Serum Creatinine Level

  12 months

• Patient Survival Rate

  12 months

• Graft Survival Rate

  12 months

• Number of Rejection Episodes

  12 months

Study Arms (2)

Tacrolimus, Immediate release

ACTIVE COMPARATOR

Tacrolimus (immediate-release) will be administered twice daily per clinical judgment of supervising physician (dosing and monitoring in accordance with center protocol) to a minimum whole blood tacrolimus concentration of at least 8 ng/mL.

Drug: Tacrolimus

Envarsus XR

EXPERIMENTAL

Envarsus XR (Tacrolimus Extended Release Oral Tablet) will be administered once daily at initial weight-based dose of 0.12 mg/kg. Dosing and monitoring thereafter predicated on clinical judgment to a minimum whole blood tacrolimus concentration of at least 8 ng/mL. When possible, patients will receive their daily dose of Envarsus using the fewest number of pills possible.

Drug: Tacrolimus Extended Release Oral Tablet

Interventions

Tacrolimus Extended Release Oral Tablet DRUG

Tacrolimus, extended-release, oral (Envarsus); 0.75 mg, 1 mg, 4 mg tablets will be administered once daily at initial weight-based dose of 0.12 mg/kg.

Also known as: Envarsus XR

Envarsus XR

Tacrolimus DRUG

Tacrolimus immediate-release, oral; 0.5 mg, 1 mg, 5 mg capsules will be administered twice daily per clinical judgment of supervising physician

Also known as: Prograf

Tacrolimus, Immediate release

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead
• Veloxis Pharmaceuticals: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Tacrolimus

Condition Hierarchy (Ancestors)

Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Amanda Alonso
• Organization: Columbia University

aa2974@cumc.columbia.edu

212-342-0261

Study Officials

• Mark Hardy, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, randomized, open-label trial examining once versus twice daily tacrolimus dosing regimen using two preparations, Envarsus vs Prograf

Study Record Dates

• First Submitted: January 29, 2018
• First Posted: April 30, 2018
• Study Start: July 26, 2018
• Primary Completion: July 17, 2020
• Study Completion: July 17, 2021
• Last Updated: July 17, 2024
• Results First Posted: July 17, 2024

Record last verified: 2024-06

Locations

US (1)