An Open-Label Study to Explore the Clinical Efficacy of GS-7977 With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant
Overview
- Phase
- Phase 2
- Intervention
- Sofosbuvir
- Conditions
- Hepatitis C
- Sponsor
- Gilead Sciences
- Enrollment
- 61
- Locations
- 15
- Primary Endpoint
- Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
The primary objective is to determine if the administration of a combination of sofosbuvir (SOF; GS-7977; PSI-7977) and ribavirin (RBV) to HCV-infected adults with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation could prevent post-transplant re-infection as determined by a sustained post-transplant virological response (HCV RNA < LLoQ) at 12 weeks post-transplant.
Participants will enroll in the pretransplant treatment phase (24 or 48 weeks). Participants enrolling for 24 weeks in the pretransplant treatment phase may receive treatment for up to an additional 24 weeks in the pretransplant retreatment phase. Participants enrolling for 48 weeks in the pretransplant treatment will have a second baseline at Week 24 for combined analysis in the pretransplant retreatment phase.
Participants who undergo liver transplant will stop all study drug 24 hours prior to transplant, and enter a 48-week follow-up phase to monitor for recurrent HCV infection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide written informed consent
- •Males or females, age \> 18 years old
- •Males must agree to consistently and correctly use a condom while their female partner agrees to use an approved form of birth control from the date of screening until 7 months after their last dose of ribavirin.
- •Confirmation of chronic HCV infection documented by at least one measurement of serum HCV RNA above the LLOQ measured at screening, and at least one of the following:
- •Positive anti-HCV antibody test, HCV RNA or HCV genotyping test at least 6 months prior to the baseline/Day 1 visit together with positive HCV RNA test and anti-HCV antibody at the time of screening, or
- •Positive HCV RNA test and anti-HCV antibody test at the time of screening together with either a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of chronic HCV infection, such as the presence of fibrosis)
- •HCV RNA \> 10\^4 IU/mL at screening
- •Patients meeting the MILAN criteria undergoing liver transplant for HCC secondary to HCV with a MELD of \< 22 and a HCC weighted MELD of ≥
- •Child-Pugh Score (CPT) ≤ 7
- •Planned management of the subject to meet United Network for Organ Sharing (UNOS) criteria, with imaging studies made available for review if required.
Exclusion Criteria
- •Females of child-bearing potential who is pregnant or nursing
- •Prior exposure to a direct-acting antiviral targeting the HCV nonstructural (NS)5B polymerase
- •Any transplant patient who has agreed to a liver transplant from a live donor.
- •Participants requiring planned induction therapy with biologics posttransplantation or with a posttransplantation immunosuppressive regimen not consistent with the following within the first 12 weeks posttransplant:
- •Solumedrol/Prednisone (tapering over approximately 7 days)
- •Tacrolimus (maintaining a serum level of 5 12 ng/mL)
- •Mycophenolate mofetil (up to 2 g/day)
- •Introduction of new maintenance immunosuppressants different from the above list is disallowed except in consultation during the first 12 weeks posttransplant
- •Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome, among other signs of decompensated cirrhosis.
- •Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis)
Arms & Interventions
SOF+RBV
Sofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first.
Intervention: Sofosbuvir
SOF+RBV
Sofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first.
Intervention: Ribavirin
Outcomes
Primary Outcomes
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
Time Frame: Posttransplant Week 12
pTVR was defined as HCV RNA \< the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
Percentage of Participants Experiencing Any Adverse Event Leading to Permanent Discontinuation of Sofosbuvir Prior to Receiving Transplant
Time Frame: Up to 48 weeks prior to transplant
Percentage of Participants With Graft Loss Following Transplant
Time Frame: Up to 48 weeks following transplant
Number of Participants Who Died
Time Frame: Up to 48 weeks following transplant
* Treatment-emergent deaths were those that occurred while taking study drug or to the minimum of 1) date of transplantation, 2) retreatment 1st dose date, or 3) last dose date + 30 days. * Only those participants who underwent liver transplantation were analyzed for death post-transplantation.
Secondary Outcomes
- Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48(Up to 48 weeks following transplant)
- Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48(Up to 48 weeks prior to transplant)
- HCV RNA and Change From Baseline in HCV RNA Through Week 8(Up to 8 weeks prior to transplant)
- Proportion of Participants With Virologic Failure Prior to Transplant(Up to 48 weeks prior to transplant)