Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients (THINKER)

June 14, 2023 updated by: University of Pennsylvania

Open-Labeled Trial Of Direct-Acting Antiviral Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors

This study is being conducted to determine safety and effectiveness of transplanting kidneys from Hepatitis C-positive donors into Hepatitis C-negative patients on the kidney transplant waitlist, who will then be treated with the appropriate direct-acting antiviral (DAA) after the single kidney transplantation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Open-labelled pilot clinical trial of Zepatier (Grazoprevir + Elbasvir), Mavyret (Glecaprevir + Pibrentasvir), Epclusa (Sofosbuvir + Velpatasvir), or another appropriate DAA in at least 75 HCV-negative subjects with end-stage renal disease receiving a kidney transplant from a HCV-positive donor. Eligible subjects will receive a kidney transplant from a deceased-donor, and then will receive DAA treatment after kidney transplantation when infection with HCV is confirmed in these kidney transplant recipients. Treatment will be complete after 12 weeks for most subjects.

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Subject:

Inclusion criteria

  • Must be waitlisted for a kidney transplant (dialysis is not a requirement if a patient is waitlisted)
  • Listed for an isolated kidney transplant with ≤2555 days of accrued transplant waiting time and/or ≤2555 days of dialysis time for blood group A, B, or O, by enrollment
  • Listed for an isolated kidney transplant with ≤1825 days of accrued transplant waiting time and/or ≤1825 days of dialysis time for blood group AB, by enrollment
  • No available living kidney donor
  • Between 30-70 years of age, by enrollment
  • Have a panel reactive antibody level ≤97%
  • eGFR <15ml/min/1.73m2 as calculated using the 4 variable MDRD equation
  • Obtained agreement for participation from the patient's treating transplant nephrologist
  • Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 months after transplantation
  • No active illicit substance abuse
  • Weigh at least 50kg
  • Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage
  • Both men and women must agree to use at least one barrier method to prevent any secretion exchange
  • Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA
  • Able to provide informed consent

Exclusion criteria

  • Hepatocellular carcinoma
  • Patients with primary focal segmental glomerulosclerosis (FSGS), FSGS recurring after previous transplant, or disease process with increased risk of causing early graft failure as per the treating nephrologist
  • HIV positive
  • HCV RNA positive (can be isolated HCV antibody positive provided the subject has no history of previously treated HCV)
  • Hepatitis B surface antigen positive
  • Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes
  • Persistently elevated liver transaminases
  • Significant hepatic fibrosis on screening elastography (≥f2 fibrosis)
  • Pregnant or nursing (lactating) women
  • Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and Zepatier
  • Waitlisted for a multi-organ transplant (e.g., pancreas-kidney, heart-kidney, etc.)

  • Significant cardiomyopathy defined as either:

    • Left ventricular ejection fraction <40% on most recent echocardiogram
    • Left ventricular ejection fraction ≥40% but <50% on most recent echocardiogram with an <5 METS of exercise tolerance
    • Reversible ischemia on stress testing without revascularization

Donor Organ Selection:

Inclusion Criteria

  • Detectable HCV RNA
  • Age ≤60 years
  • Study modified Kidney donor profile index (KDPI) score ≤0.856 - calculated as if the kidney were HCV-negative (https://optn.transplant.hrsa.gov/resources/allocation-calculators/kdpi-calculator/)

Exclusion Criteria

  • Anatomical issues in the kidney allograft that raise the risk of post-transplant complications (e.g., number or length of renal arteries or veins)
  • Confirmed HIV positive
  • Confirmed HBV positive (positive Hepatitis B surface antigen and/or HBV DNA)
  • Known previously failed treatment for HCV using a regimen with a direct-acting antiviral (can have received interferon monotherapy and/or interferon + ribavirin combination therapy)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Direct-acting antiviral treatment for HCV
Drug: Zepatier
Zepatier (grazoprevir 100mg and elbasvir 50 mg once daily) is taken by mouth for 12 weeks unless a genetic variation is detected. In this case treatment with Zepatier will be extended to 16 weeks. Study subjects with treatment failure will be provided open-label Zepatier + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.
Drug: Mavyret
Mavyret (glecaprevir 100 mg and pibrentasvir 40 mg) is taken by mouth for 8 weeks. Study subjects with treatment failure will be provided an alternative DAA + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects Cured
Time Frame: Baseline to 24 weeks
Subjects with post-treatment sustained virologic response (SVR) = Number of subjects with negative HCV RNA 12 weeks after completing therapy / number of subjects treated post-kidney transplantation
Baseline to 24 weeks
Number of Subjects With SAE Attributable to HCV Therapy
Time Frame: Baseline to 52 weeks
Number of subjects with major adverse events attributable to HCV therapy in post-kidney transplant
Baseline to 52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Principal Investigator: Stacey Prenner, MD, University of Hospital of Pennsylvania
  • Principal Investigator: Peter Reese, MD, MSCE, University of Hospital of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2016

Primary Completion (Actual)

March 1, 2022

Study Completion (Actual)

December 1, 2022

Study Registration Dates

First Submitted

April 15, 2016

First Submitted That Met QC Criteria

April 15, 2016

First Posted (Estimated)

April 19, 2016

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

June 14, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 823833

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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