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Conversion to Envarsus Post Kidney Transplant Protects Against BK Infection

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ClinicalTrials.gov Identifier: NCT03762473
Recruitment Status : Not yet recruiting
First Posted : December 3, 2018
Last Update Posted : December 3, 2018
Sponsor:
Information provided by (Responsible Party):
Graham C. Towns, University of Alabama at Birmingham

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.

Condition or disease Intervention/treatment Phase
Renal Transplant Infection Drug: Study Group Drug: Control Group Phase 2

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). Patient will be managed using standard of care for the investigator's center (thymoglobulin induction, tacrolimus/mycophenolate/prednisone). Target tacrolimus level is 8-12 for the first 6 months and 6-9 thereafter. BK urine/serum is monitored at 1, 3, 6, 9, 12 months. A population of 100 patients is calculated to show significant difference for p value < .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 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.

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Conversion From Tacrolimus to Envarsus in Rapid Metabolizers Post Kidney Transplant Protects Against BK Infection
Estimated Study Start Date : March 1, 2019
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Tacrolimus

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 Name: 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 Name: Tacrolimus




Primary Outcome Measures :
  1. Participants will experience less BK infection episodes based on viruria results. [ Time Frame: From baseline to 30 days ]
    The evidence of BK virus infection will be measured by viruria >500 copies.

  2. Participants will experience less BK infection episodes based on viremia results. [ Time Frame: From baseline to 30 days ]
    The evidence of BK virus infection will be measured by viremia >500 copies.

  3. Participants will experience less BK infection episodes based on nephropathy results. [ Time Frame: From baseline to 30 days ]
    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).

  4. Participants will experience less BK infection episodes based on viruria results. [ Time Frame: From baseline to 120 days ]
    The evidence of BK virus infection will be measured by viruria >500 copies.

  5. Participants will experience less BK infection episodes based on viremia results. [ Time Frame: From baseline to 120 days ]
    The evidence of BK virus infection will be measured by viremia >500 copies.

  6. Participants will experience less BK infection episodes based on nephropathy results. [ Time Frame: From baseline to 120 days ]
    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).

  7. Participants will experience less BK infection episodes based on viruria results. [ Time Frame: From baseline to 210 days ]
    The evidence of BK virus infection will be measured by viruria >500 copies.

  8. Participants will experience less BK infection episodes based on viremia results. [ Time Frame: From baseline to 210 days ]
    The evidence of BK virus infection will be measured by viremia >500 copies.

  9. Participants will experience less BK infection episodes based on nephropathy results. [ Time Frame: From baseline to 210 days ]
    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).

  10. Participants will experience less BK infection episodes based on viruria results. [ Time Frame: From baseline to 300 days ]
    The evidence of BK virus infection will be measured by viruria >500 copies.

  11. Participants will experience less BK infection episodes based on viremia results. [ Time Frame: From baseline to 300 days ]
    The evidence of BK virus infection will be measured by viremia >500 copies.

  12. Participants will experience less BK infection episodes based on nephropathy results. [ Time Frame: From baseline to 300 days ]
    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).

  13. Evaluate the safety of Envarsus treatment as assessed by CTCAE v4.0. [ Time Frame: From baseline to 30 days ]
    Safety will be assessed for all Grade 3 or higher infection

  14. Evaluate the safety of Envarsus treatment as assessed by CTCAE v4.0. [ Time Frame: From baseline to 120 days ]
    Safety will be assessed for all Grade 3 or higher infection

  15. Evaluate the safety of Envarsus treatment as assessed by CTCAE v4.0. [ Time Frame: From baseline to 210 days ]
    Safety will be assessed for all Grade 3 or higher infection

  16. Evaluate the safety of Envarsus treatment as assessed by CTCAE v4.0. [ Time Frame: From baseline to 300 days ]
    Safety will be assessed for all Grade 3 or higher infection


Secondary Outcome Measures :
  1. Evaluate the effect of Envarsus conversion as evidenced by a 15% decrease in estimated glomerular filtration rate (GFR) and proteinuria. [ Time Frame: From baseline to 30 days ]
    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

  2. Evaluate the effect of Envarsus conversion as evidenced by a 15% decrease in estimated glomerular filtration rate (GFR) and proteinuria. [ Time Frame: From baseline to 120 days ]
    This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria

  3. Evaluate the effect of Envarsus conversion as evidenced by a 15% decrease in estimated glomerular filtration rate (GFR) and proteinuria. [ Time Frame: From baseline to 210 days ]
    This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria

  4. Evaluate the effect of Envarsus conversion as evidenced by a 15% decrease in estimated glomerular filtration rate (GFR) and proteinuria. [ Time Frame: From baseline to 300 days ]
    This assessment will include incidence of rejection, graft failure, graft dysfunction as defined by a 15% decrease in estimated GFR and proteinuria



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  • Pt 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 wither 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 participant 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03762473


Contacts
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Contact: Tina W Ayer, BS 205-996-2577 tayer@uabmc.edu

Locations
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United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: Graham C Towns, MD    205-934-9045    gtowns@uabmc.edu   
Contact: Tina W Ayer, BS    205-996-2577    tayer@uabmc.edu   
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
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Principal Investigator: Graham C Towns, MD University of Alabama at Birmingham

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Responsible Party: Graham C. Towns, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT03762473     History of Changes
Other Study ID Numbers: IRB-300001068
First Posted: December 3, 2018    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

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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

Keywords provided by Graham C. Towns, University of Alabama at Birmingham:
Envarsus

Additional relevant MeSH terms:
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Infection
Communicable Diseases
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action