A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients

Study Overview
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Brief Summary
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The Transplanting Hepatitis C Kidneys into Negative KidnEy Recipients [THINKER-NEXT] study will include adult kidney transplant candidates without hepatitis C virus (HCV) infection on the transplant waiting list who will consent to kidney transplantation from a deceased donor infected with HCV, followed by treatment with a direct acting antiviral. The one-year allograft function and one-year risk of CMV infection will be compared between THINKER-NEXT kidney transplant recipients and matched recipients who received hepatitis C uninfected kidney transplants (these patients are called Transplant Cohort). The mortality rate of kidney transplant candidates who enroll in THINKER-NEXT and consent to offers of kidneys from HCV-infected donors will be compared to matched wait-listed patients who do not consent to receive HCV-infected kidneys (these patients are called Wait-list Cohort). Lastly, renal pathologic findings will be compared among HCV-viremic donors and HCV-negative comparator donors.

Official Title
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A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Epclusa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide informed consent Active waiting list status for isolated kidney transplant 18 years of age or older No living kidney donor Panel reactive antibody (PRA) ≤97% (most recent cPRA at time of screening). Patients with a PRA of 98-100% at screening can be included unless patient has a most recent cytotoxic PRA of >25% or calculated PRA >50% where multiple moderate level HLA antibodies exist and in the opinion of the local site investigator represents substantial HLA sensitization. If patient has a PRA of 98-100%, the donor-recipient pair must meet additional eligibility criteria. Exclusion Criteria: Hepatocellular carcinoma Hepatitis B surface antigen and/or DNA positive Active Hepatitis C infection HIV RNA-positive or HIV antibody positive Other chronic liver disease (excluding non-alcoholic fatty liver disease [NAFLD] with normal liver enzymes) Persistently elevated liver transaminases (defined as the upper limit of normal at the reference laboratory) Advanced hepatic fibrosis or cirrhosis Primary Focal Segmental Glomerulosclerosis (FSGS), FSGS recurring in initial transplant, or other disease process at high risk of early graft failure per the treating transplant nephrologist Current use of amiodarone or dronedarone (due to interaction with sofosbuvir) Transplant candidate requires antibody desensitization protocol for transplantation Female who is pregnant, planning to become pregnant during the study, or breast-feeding Participation in another interventional study, from a period starting 6 months prior to screening to last study visit, that the study PIs judge would interfere with either the aims or the safety of the THINKER-NEXT study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epclusa (sofosbuvir/velpatasvir)<br>Epclusa is taken by mouth for 12 weeks as per the FDA label. | Drug: Epclusa<br>* All patients will receive 12 weeks of sofosbuvir/velpatasvir as per the FDA label.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-treatment sustained virologic response (SVR) to direct-acting antiviral (DAA) | The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR-12; negative HCV RNA 12 weeks after completing Epclusa therapy)/(number of subjects treated with Epclusa post-kidney transplantation) | Baseline to 24 weeks |