A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients (THINKER-NEXT)

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 survival rate of patients opting-in for offers of kidneys from HCV-viremic donors will be compared to the survival rate of matched comparators from the kidney transplant waitlist who did not consent to receive offers of a HCV-viremic kidney. Lastly, renal pathologic findings will be compared among HCV-viremic donors and HCV-negative comparator donors.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease
• Intervention / Treatment: Drug: Epclusa

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital/University of Miami
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • New York Presbyterian Hospital/Columbia University
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Gilead Sciences
• Investigators: Principal Investigator: Peter Reese, MD, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2021
• Primary Completion (Actual): July 15, 2025
• Study Completion (Actual): February 25, 2026

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Pathological Conditions, Signs and Symptoms; Kidney Failure, Chronic; Anti-Infective Agents; Antiviral Agents; sofosbuvir-velpatasvir drug combination
• Other Study ID Numbers: 10067385; U01DK126654 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No