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

NCT04075916 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 10067385U01DK126654
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

End Stage Renal Disease

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Epclusa (sofosbuvir/velpatasvir)

EXPERIMENTAL

Epclusa is taken by mouth for 12 weeks as per the FDA label.

Drug: Epclusa

Interventions

Epclusa DRUG

All patients will receive 12 weeks of sofosbuvir/velpatasvir as per the FDA label.

Epclusa (sofosbuvir/velpatasvir)

Eligibility Criteria

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

You may qualify if:

• Able to provide informed consent
• Active waiting list status for isolated kidney transplant
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Gilead Sciences: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

Jackson Memorial Hospital/University of Miami

Miami, Florida, 33136, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

New York Presbyterian Hospital/Columbia University

New York, New York, 10032, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

sofosbuvir-velpatasvir drug combination

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Peter Reese, MD, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: September 3, 2019
• Study Start: June 22, 2021
• Primary Completion: July 15, 2025
• Study Completion: February 25, 2026
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (11)