Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients

• Status: Active, not recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Elbasvir-grazoprevir drug combination

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)