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

Phase 4

Completed

Interventions: Drug: Sofosbuvir/Velpatasvir
Drug: Sofosbuvir/Velpatasvir/Voxilaprevir

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Sofosbuvir/Velpatasvir/Voxilaprevir	Single Arm: Sofosbuvir/Velpatasvir Dosage: 400mg/100mg. Once daily for 12 weeks.
Treatment Arm	Sofosbuvir/Velpatasvir	Single Arm: Sofosbuvir/Velpatasvir Dosage: 400mg/100mg. Once daily for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Proportion of Participants With HCV RNA Level Below Limits of Quantification (LOQ)	12 weeks after end of treatment	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.

Secondary Outcome Measures

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

Locations (6): University of California, San Francisco
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San Francisco, California, United States
Baylor University Medical Center - Dallas
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Dallas, Texas, United States
Houston Methodist Hospital
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Houston, Texas, United States
Columbia University
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New York, New York, United States
University of Colorado Denver
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Aurora, Colorado, United States
Piedmont Research Institute
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Atlanta, Georgia, United States