Prevention of De Novo HCV With Antiviral HCV Therapy Post-Liver and Post-Kidney Transplant (PRO-ACT:)

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C; Transplantation Disease Transmission
• Intervention / Treatment: Drug: Sofosbuvir/Velpatasvir; Drug: Sofosbuvir/Velpatasvir/Voxilaprevir

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Research Institute
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center - Dallas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival Rate of Patients and Their Allografts 6 Months Post Transplant	Graft and patient survival at 24 weeks after transplant	6 months from time of liver transplant

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Claus Niemann, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2018
• Primary Completion (Actual): December 21, 2019
• Study Completion (Actual): August 13, 2020

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): March 3, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
• Other Study ID Numbers: 18-24323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes