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

Primary Purpose

End Stage Renal Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Epclusa
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Renal Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 (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 of any investigational agent or approved medication, or participation in another kind interventional study that the responsible investigator deems to be an exclusion from period 6 months prior to screening to last study visit

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • Jackson Memorial Hospital/University of MiamiRecruiting
  • Johns Hopkins
  • Massachusetts General HospitalRecruiting
  • New York Presbyterian Hospital/Columbia UniversityRecruiting
  • University of CincinnatiRecruiting
  • Cleveland Clinic
  • Hospital of the University of PennsylvaniaRecruiting
  • Medical University of South CarolinaRecruiting
  • Vanderbilt UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Epclusa (sofosbuvir/velpatasvir)

Arm Description

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

First Posted
August 29, 2019
Last Updated
August 3, 2023
Sponsor
University of Pennsylvania
Collaborators
Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT04075916
Brief Title
A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients
Acronym
THINKER-NEXT
Official Title
A Trial of Transplanting Hepatitis C Kidneys Into Hepatitis C-Negative Kidney Recipients
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 22, 2021 (Actual)
Primary Completion Date
January 15, 2025 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania
Collaborators
Gilead Sciences, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
450 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Epclusa (sofosbuvir/velpatasvir)
Arm Type
Experimental
Arm Description
Epclusa is taken by mouth for 12 weeks as per the FDA label.
Intervention Type
Drug
Intervention Name(s)
Epclusa
Intervention Description
All patients will receive 12 weeks of sofosbuvir/velpatasvir as per the FDA label.
Primary Outcome Measure Information:
Title
Post-treatment sustained virologic response (SVR) to direct-acting antiviral (DAA)
Description
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)
Time Frame
Baseline to 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Reese, MD, PhD
Phone
(307) 22-THINK
Email
thinker@med.upenn.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Therese Bitermann, MD, MSCE
Phone
(307) 22-THINK
Email
thinker@med.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Reese, MD, PhD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shikha Mehta, MD
Email
smehta@uabmc.edu
Facility Name
Jackson Memorial Hospital/University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Goldberg, MD, MSCE
Email
dsgoldberg@med.miami.edu
First Name & Middle Initial & Last Name & Degree
Javier Pagan, MD
Email
jap88@miami.edu
First Name & Middle Initial & Last Name & Degree
David Goldberg, MD, MSCE
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raymond Chung, MD
Email
rtchung@partners.org
First Name & Middle Initial & Last Name & Degree
Meghan Sise, MD
Email
msise@partners.org
First Name & Middle Initial & Last Name & Degree
Raymond Chung, MD
Facility Name
New York Presbyterian Hospital/Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Verna, MD
Email
ev77@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Sumit Mohan, MD
Email
sm2206@cumc.columbia.edu
First Name & Middle Initial & Last Name & Degree
Elizabeth Verna, MD
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steve Woodle, MD
Email
steve.woodle@uc.edu
First Name & Middle Initial & Last Name & Degree
Steve Woodle, MD
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Huml, MD
Email
humla@ccf.org
First Name & Middle Initial & Last Name & Degree
Anne Huml, MD
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adam Mussell, MA
Phone
215-746-4177
Email
adam.mussell@uphs.upenn.edu
First Name & Middle Initial & Last Name & Degree
Therese Bittermann, MD, MSCE
First Name & Middle Initial & Last Name & Degree
Peter Reese, MD, MSCE
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John McGillicuddy, MD
Email
mcgillij@musc.edu
First Name & Middle Initial & Last Name & Degree
John McGillicuddy, MD
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Shaffer, MD, FACS
Email
david.shaffer@vumc.org
First Name & Middle Initial & Last Name & Degree
Rachel Forbes, MD, MBA
Email
rachel.forbes@vumc.org
First Name & Middle Initial & Last Name & Degree
David Shaffer, MD, FACS

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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