Prevention of De Novo HCV With Antiviral HCV Therapy Post-Liver and Post-Kidney Transplant

Study Overview
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Brief Summary
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In this study, subjects that do not have Hepatitis C virus (HCV) will be transplanted with livers or kidneys from donors who do have HCV. Medications that are used to treat HCV will be given to the study subjects shortly after transplant to protect them from developing the problems HCV can cause to the liver.

Official Title
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PRO-ACT: Prevention of De Novo HCV With Antiviral HCV Therapy Post-Liver

Conditions
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Hepatitis C, Transplantation Disease Transmission

Intervention / Treatment
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* Drug: Sofosbuvir/Velpatasvir
* Drug: Sofosbuvir/Velpatasvir/Voxilaprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥ 18 year-old), wait-listed for primary kidney or liver transplant without a potential suitable living donor or for simultaneous liver kidney transplant; HCV non-infected at the time of transplant. Subjects who were previously HCV infected but who have had documented SVR12 are eligible to participate; Agree to use two methods of birth control during the study; Donor characteristics: serum HCV NAT-positive and negative for hepatitis B surface antigen. For liver transplant: pre-donation liver biopsy with no fibrosis (F0) or minimal fibrosis (F1). For kidney transplant: kidney donor profile index < 85%. Exclusion Criteria: Donor and/or recipient HIV infection Subject pregnant or nursing Donor and/or recipient Hepatitis B surface antigen positive Kidney-pancreas transplant Single organ liver recipients who received hemodialysis for more than 7 days prior to liver transplantation Kidney recipients: on dialysis for > 5 years at time of Screening; subjects sensitized with panel reactive antibody > 80%; for single organ kidney transplant, subjects with advanced liver fibrosis (Knodell stage 3) or cirrhosis Individuals being treated with and needing to continue rifabutin, rifampin, carbamazepine, phenytoin, phenobarbital, oxcarbazepine, St. John's wort (Hypericum perforatum), medium- or high-dose rosuvastatin or atorvastatin, or high-dose proton pump inhibitors (See Concomitant Medications). Individuals treated with amiodarone within 42 days of organ transplant.
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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Single Arm: Sofosbuvir/Velpatasvir Dosage: 400mg/100mg. Once daily for 12 weeks. | Drug: Sofosbuvir/Velpatasvir<br>* Sofosbuvir/Velpatasvir starting early post-transplant for total of 12 weeks.<br>Drug: Sofosbuvir/Velpatasvir/Voxilaprevir<br>* Only for patients who fail initial treatment with Sofosbuvir/Velpatasvir. Dosage: 400mg/100mg/100mg daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With HCV RNA Level Below Limits of Quantification (LOQ) | The primary outcome was sustained virologic response, defined as HCV RNA below the lower limit of quantification 12 weeks after treatment completion (SVR12). Secondary outcomes included the proportion of patients with SVR24 defined as HCV RNA < lower limit of quantification 24 weeks after the end of treatment; with viral relapse defined as HCV RNA <LLOQ at end of treatment with subsequent quantifiable HCV RNA; and with on-treatment virologic breakthrough defined as > 1 log increase in viral RNA after treatment week 1. Safety was measured as the adverse events and serious adverse events attributed by the investigator to HCV infection or antiviral therapy; the proportion of recipients who prematurely discontinued antiviral therapy before the planned end of treatment; and patient and graft survival at 6 months post-transplant. | 12 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as Measured by the Proportion of Participants Who Prematurely Discontinue Antiviral Therapy Before the Planned End of Treatment | 1 of 23 patients prematurely discontinued antiviral therapy due to intercurrent graft-versus-host disease that progressed to multiorgan failure. | 12 weeks after start of treatment |