Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients (THINKER)

University of Pennsylvania

Status and phase

Completed

Phase 2

Phase 1

Conditions

End Stage Renal Disease

Treatments

Drug: Zepatier

Drug: Mavyret

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02743897

823833

Details and patient eligibility

About

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.

Full 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.

Enrollment

62 patients

Sex

All

Ages

30 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)