Conversion to Envarsus Post Kidney Transplant Protects Against BK Infection

NCT03762473 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB-300001068
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Transplant Infection

Keywords

Envarsus

Outcome Measures

Primary Outcomes (16)

• 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 Outcomes (4)

• Evaluate the Effect of Envarsus Conversion as Evidenced 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.

  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.

  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.

  at 300 days

Study Arms (2)

Study Group

EXPERIMENTAL

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

Control Group

ACTIVE COMPARATOR

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

Interventions

Study Group DRUG

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.

Also known as: tacrolimus extended-release tablets

Study Group

Control Group DRUG

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.

Also known as: Tacrolimus

Control Group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Interventions

Control Groups; Tacrolimus

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Graham Towns, MD
• Organization: University of Alabama at Birmingham

gtowns@uabmc.edu

(205)934-1801

Study Officials

• Graham C Towns, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 27, 2018
• First Posted: December 3, 2018
• Study Start: May 9, 2019
• Primary Completion: March 16, 2022
• Study Completion: March 16, 2022
• Last Updated: July 27, 2023
• Results First Posted: July 27, 2023

Record last verified: 2023-07

Locations

US (1)