Conversion to Envarsus Post Kidney Transplant Protects Against BK Infection

Conversion From Tacrolimus to Envarsus in Rapid Metabolizers Post Kidney Transplant Protects Against BK Infection

The purpose of this study is to assess if the use of Envarsus in place of Tacrolimus-immediate release (IR) in rapid metabolizers post kidney transplant will reduce incidence of BK infection. Efficacy evaluations will include measurement of urine and serum BK values at specified time points and review of any biopsy for BK virus nephropathy. Incidence of rejection, graft failure, and graft dysfunction will also be measured at specified time points.

Study Overview

• Status: Completed
• Conditions: Renal Transplant Infection
• Intervention / Treatment: Drug: Study Group; Drug: Control Group

Detailed Description

This will be a single center prospective case control study. The investigators expect 40% of patients will develop BK viruria, 20% BK viremia, 5% BK viral nephropathy (BKVN). Patients will be managed using standard of care for the investigator's center (thymoglobulin induction, tacrolimus/mycophenolate/prednisone). Target tacrolimus level is 8-12 ng/mL for the first 6 months post transplant and 6-9 ng/mL thereafter. BK urine/serum is monitored at 1, 3, 6, 9, 2 months post transplant. A population of 100 patients is calculated to show significant difference for p value < 0.05.

Population:

Study Group: Post transplant patients (kidney transplant alone) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, and negative BK screening at post-transplant month 1, who have a tacrolimus concentration/dose of < 1 and a steady state therapeutic level will be eligible. Patients who consent will be converted to Envarsus at 20% reduction in tacrolimus dose.

Control Group: Post transplant patients (kidney transplant alone performed between 10-2016 and time of enrollment) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at post-transplant month 1 and tacrolimus concentration/dose of < 1 at post-transplant month 1, and BK data available for months 2, 3, 6, 9,12 post transplant.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years of age at the time of study entry
• Recipient of a deceased or living donor kidney transplantation
• Maintenance immunosuppression consisting of tacrolimus/ mycophenolate mofetil (MMF)/mycophenolic acid (MPA) (≥1000 mg/720 mg daily) ± prednisone (≤10 mg/day)
• Patient is less than or at 8 weeks post transplant with a negative serum BK Virus screen at 3-4 weeks post transplant
• Patient has a tacrolimus drug dose/concentration of > 1 with therapeutic tacrolimus levels.
• Women of childbearing potential defined as all women physiologically capable of becoming pregnant, must have reviewed Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) and have a negative pregnancy test upon study entry.
• Female (and male) subjects with reproductive potential must agree to use a highly effective method of birth control for the duration of the study. Please note that according to the US product information for MMF/MPA, two reliable forms of contraception must be used simultaneously unless female sterilization, male sterilization, post-menopausal status or total abstinence is the chosen method.

Exclusion Criteria:

• Inability or unwillingness of a patient to give written informed consent or comply with study protocol
• History of graft loss from acute rejection within 1 year after any previous kidney transplant
• History of previous liver, heart, pancreas, or lung transplant
• History of cellular rejection of current allograft prior to enrollment.
• Serum BK virus ≥500 copies/ml by polymerase chain reaction (PCR) at the time of study entry
• Female subjects who are pregnant or breast feeding
• Participation in any other studies with investigational drugs or regimens in the preceding year from the time of study entry
• Any condition or prior treatment which, in the opinion of the investigator, precludes study participation
• Patients requiring the use of azathioprine or a class of drugs that inhibit the mammalian target of rapamycin (mTOR inhibitors)
• Patients with active peptic ulcer disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group; Post transplant patients (kidney transplant alone) with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, and negative BK screening at month 1, whom have a concentration/dose of < 1 and a steady state therapeutic level will be eligible. Patients will be converted to envarsus at 20% reduction in dose.	Drug: Study Group; Patients will convert from current tacrolimus dose to an Envarsus dose that is 80% of the total tacrolimus dose. They will take envarsus once daily in the morning and have 24 hour trough levels monitored at the standard of care interval for tacrolimus. Dosing will be titrated to achieve goal levels.; Other Names: tacrolimus extended-release tablets
Active Comparator: Control Group; Post transplant patients (kidney transplant alone) performed between 10-2016 and time of enrollment with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at month 1 and concentration/dose of < 1 at month 1, and BK data available and month 2,3, 6,9,12.	Drug: Control Group; Post transplant patients (kidney transplant alone) performed between 10-2016 and time of enrollment with standard of care immunosuppression, no prior rejection, prior BK or opportunistic infection, whom had a negative BK screening at month 1 and concentration/dose of < 1 at month 1, and BK data available and month 2,3, 6,9,12.; Other Names: Tacrolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants Will Experience Less BK Infection Episodes Based on Viruria Results.	The evidence of BK virus infection will be measured by viruria >500 copies.	From baseline to 30 days
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.	The evidence of BK virus infection will be measured by viremia >500 copies.	From baseline to 30 days
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.	The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).	From baseline to 30 days
Participants Will Experience Less BK Infection Episodes Based on Viruria Results.	The evidence of BK virus infection will be measured by viruria >500 copies.	From baseline to 120 days
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.	The evidence of BK virus infection will be measured by viremia >500 copies.	From baseline to 120 days
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.	The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).	From baseline to 120 days
Participants Will Experience Less BK Infection Episodes Based on Viruria Results.	The evidence of BK virus infection will be measured by viruria >500 copies.	From baseline to 210 days
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.	The evidence of BK virus infection will be measured by viremia >500 copies.	From baseline to 210 days
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.	The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).	From baseline to 210 days
Number of Participants With Viruria >500 Copies	Participants will experience less BK infection episodes based on viruria reported with >500 copies.	at 300 days
Participants Will Experience Less BK Infection Episodes Based on Viremia Results.	The evidence of BK virus infection will be measured by viremia >500 copies.	at 300 days
Participants Will Experience Less BK Infection Episodes Based on Nephropathy Results.	The evidence of BK virus infection will be measured by nephropathy as defined by Banff classification (sv 40 positivity with or without tubulitis or if/ta).	at 300 days
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.	Safety will be assessed for all Grade 3 or higher infection	From baseline to 30 days
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.	Safety will be assessed for all Grade 3 or higher infection	From baseline to 120 days
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.	Safety will be assessed for all Grade 3 or higher infection	From baseline to 210 days
Evaluate the Safety of Envarsus Treatment as Assessed by CTCAE v4.0.	Safety will be assessed for all Grade 3 or higher infection	at 300 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.	This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated glomerular filtration rate (GFR) and proteinuria	From baseline to 30 days
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.	This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria	From baseline to 120 days
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.	This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria	From baseline to 210 days
Evaluate the Effect of Envarsus Conversion as Evidenced by a 15% Decrease in Estimated Glomerular Filtration Rate (GFR) and Proteinuria.	This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria	at 300 days

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Graham C Towns, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2019
• Primary Completion (Actual): March 16, 2022
• Study Completion (Actual): March 16, 2022

Study Registration Dates

• First Submitted: August 27, 2018
• First Submitted That Met QC Criteria: November 30, 2018
• First Posted (Actual): December 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Envarsus
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: IRB-300001068

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No