Clinical trial NCT02743897: Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients
Official title: Open-Labeled Trial Of Direct-Acting Antiviral Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: End Stage Renal Disease
Keywords: end-stage renal disease
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-04-19
Enrollment: 62
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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)

Primary outcomes:
measure: Number of Subjects Cured
timeFrame: Baseline to 24 weeks
measure: Number of Subjects With SAE Attributable to HCV Therapy
timeFrame: Baseline to 52 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Hospital of Pennsylvania
name: Stacey Prenner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Hospital of Pennsylvania
name: Peter Reese, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
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