Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant

Study Overview
=================
Brief Summary
-----------------
This is a proof of concept, single center study for the donation of HCV-positive kidney to HCV negative recipient patients, with preemptive, interventional treatment with 12 weeks of commercially available DAA therapy to prevent HCV transmission upon transplantation.

Detailed Description
-----------------
The goal of this study is to determine if preoperative dosing and sustained administration of pan-genotypic DAA therapy after kidney transplantation prevents the transmission of hepatitis C virus (HCV) infection from an HCV positive donor kidney to an HCV naïve recipient.

Official Title
-----------------
Pan-genotypic Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant

Conditions
-----------------
Kidney Failure, Kidney Diseases, Hepatitis C

Intervention / Treatment
-----------------
* Drug: glecaprevir/pibrentasvir tablets


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Met MGH transplant center criteria and already listed for kidney transplant No available living kidney donor Has ≤ 730 days (two years) of accrued transplant waiting time if blood type A and ≤ 1095 days of accrued transplant waiting time if blood type B or O. On chronic hemodialysis or peritoneal dialysis or has a glomerular filtration rate <15mL/min/1.73m2 at the time of screening Must agree to birth control. Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy and at least one barrier method Weigh at least 50kg Serum ALT within normal limits with no history of liver disease Able to sign informed consent Exclusion Criteria: AB blood type BMI > 35 Any liver disease in recipient Pregnant or nursing (lactating) women Known allergy or intolerance to tacrolimus that would require administration of cyclosporine rather than tacrolimus given the known drug-drug interaction between cyclosporine and Mavyret Cardiomyopathy (LV ejection fraction < 50%) Albumin < 3g/dl or platelet count < 75 x 103/mL Positive donor specific antibodies or positive cross match deemed to be clinically relevant and increasing risk of rejection per the transplant surgeon or nephrologist Positive donor specific antibodies or positive cross match deemed to be clinically relevant and increasing risk of rejection per the transplant surgeon or nephrologist HCV RNA positive Hepatitis B surface antigen positive Any known liver disease or elevated liver transaminases Patients with primary focal segmental glomerulosclerosis (FSGS), FSGS recurring after previous transplant, or disease process with increased risk of causing early graft failure as assessed by the transplant nephrologist and/or the investigator team Any contra-indication to kidney transplantation per MGH center protocol Patients on the following medications who cannot stop therapy: carbamazepine, rifampin, St. John's wort, and ethinyl estradiol-containing oral contraceptives.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment with Mavyret (glecaprevir/pibrentasvir) for HCV<br>12 weeks of treatment with Mavyret | Drug: glecaprevir/pibrentasvir tablets<br>* 12 weeks of treatment with Mavyret<br>* Other names: Mavyret;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undetectable HCV RNA in blood | Negative HCV viral RNA at 12 weeks after the last dose of treatment as determined by blood test | 12 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation) | Safety of Mavyret therapy in the kidney transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient. | 12 weeks post treatment | 
| Tolerability (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation | Tolerability of Mavyret therapy in the kidney transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient. | 12 Weeks post treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CKD, HCV, Hepatitis C, Transplant