Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant

Study Overview
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Brief Summary
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Proof of concept, open-label single center study for the donation of HCV positive kidneys to HCV negative patients, with preemptive, interventional treatment to prevent HCV transmission upon transplantation.

Detailed Description
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The study objective is to determine if the administration of grazoprevir and elbasvir (with or without ribavirin) for 12-16 weeks after kidney transplantation prevents the spread of HCV infection from a donor kidney with known HCV genotype 1 or 4 infection to a HCV negative recipient as evidenced by a negative HCV viral RNA at 12 weeks post treatment

Official Title
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A Proof of Concept Study of Preemptive Treatment With Grazoprevir and Elbasvir for Donor HCV Positive to Recipient HCV Negative Kidney Transplant

Conditions
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Renal Failure

Intervention / Treatment
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* Drug: elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must meet Massachusetts General Hospital (MGH) transplant center criteria and already be listed for isolated 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 Weight ≥ 50kg Serum alanine transaminase (ALT) within normal limits Exclusion Criteria: AB blood type Body mass index (BMI > 35 History of liver disease Pregnant or nursing (lactating) women Cardiomyopathy (LV ejection fraction < 50%) Positive crossmatch or positive donor specific antibodies Human immunodeficiency virus (HIV) positive Hepatitis C virus (HCV) RNA positive Hepatitis B virus (HBV) surface antigen positive Any contraindication to kidney transplant per MGH center protocol

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Elbasvir/grazoprevir for HCV+ kidney transplant recipients<br>Elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor Subjects receive first dose on-call to operating room, and continue daily for 12 weeks. Treatment length is extended to 16 weeks and ribavirin (daily dose 1000 mg for those <75 kg and 1200 mg for those ≥75 kg) if subject receives a kidney from a donor who is infected with HCV containing resistance-associated variants (RAV). | Drug: elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination)<br>* Elbasvir (50mg) / grazoprevir (100mg) (fixed dose combination) treatment for Hepatitis C virus (HCV)-naive recipients who receive a kidney transplant from a deceased, HCV-infected donor Subjects receive first dose on-call to operating room, and continue daily for 12 weeks. Treatment length is extended to 16 weeks and ribavirin (daily dose 1000 mg for those <75 kg and 1200 mg for those ≥75 kg) if subject receives a kidney from a donor who is infected with HCV containing resistance-associated variants (RAV).<br>* Other names: Zepatier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Undetectable HCV RNA at SVR12 | Sustained virologic response at 12-weeks post-treatment (SVR12), as defined by negative HCV viral load, after 12-16 weeks of elbasvir/grazoprevir treatment in patients who receive a kidney transplant from a deceased donor infected with HCV. | 12 weeks post-treatment (24 weeks post-transplant) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Undetectable Serum HCV RNA at Study Day 7, 14, 28, 56, 84, 112, 168, 252, 365 | Subjects had Hepatitis C viral load assessed at each study visit. Here we looked at the proportion of subjects with undetectable serum HCV RNA at study day 7, 14, 28, 56, 84, 112, 168, 252, 365. | 1 year post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplant, hemodialysis, peritoneal dialysis, renal failure