Hepatitis C Virus (HCV) infection (all genotypes) in patients who have been placed on a wait list for liver transplantation from a deceased doner for hepatocellular carcinoma (HCC). MedDRA version: 14.1 Level: SOC Classification code 10021881 Term: Infections and infestations System Organ Class: 10021881 - Infections and infestations MedDRA version: 14.1 Level: PT Classification code 10019744 Term: Hepatitis C System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Sofosbuvir
Product Code: GS-7977
Pharmaceutical Form: Tablet
INN or Proposed INN: Sofosbuvir
CAS Number: 1190307-88-0
Current Sponsor code: GS-7977
Concentration unit: mg milligram(s)
Co
Sponsors
Gilead Sciences Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide written informed consent 2. Males or females, age > 18 years old 3. Confirmation of chronic HCV infection 4. HCV RNA > 104 IU/mL at Screening 5. Patients meeting the MILAN criteria undergoing liver transplant for HCC secondary to HCV with a MELD of =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Prior exposure to a direct-acting antiviral targeting the HCV NS5b polymerase 2. Any transplant patient who has agreed to a liver transplant from a live donor 3. Subjects requiring planned induction therapy with biologics post-transplantation or with a post-transplantation immunosuppressive regimen 4. Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome, among other signs of decompensated cirrhosis 5. Recent (within 4 weeks of screening) episode of infection requiring systemic antibiotics 6. Pregnant or nursing female or male with pregnant female partner 7. Chronic liver disease of a non-HCV etiology 8. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV) 9. Contraindications to RBV therapy 10. History of malignancy diagnosed or treated within 5 years 11. History of clinically significant hemoglobinopathy 12. Chronic use of systemically administered immunosuppressive agents 13. History of previous solid organ transplantation 14. Evidence of renal impairment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 12 weeks after transplant;Main Objective: The primary objective of this study is to determine if the administration of a combination of GS-7977 and ribavirin to HCV-infected subjects with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can prevent post-transplant reinfection as determined by a sustained post-transplant virological response (HCV RNA <LLoQ) at 12 weeks post-transplant.;Secondary Objective: ? To determine if the administration of a combination of GS-7977 and ribavirin to HCV-infected Subjects with HCC prior to undergoing liver transplantation can elicit a sustained viral response (SVR12). ? To evaluate the safety and tolerability of a combination of GS-7977 and ribavirin in HCV-infected subjects prior to undergoing liver transplantation. ? To evaluate the HCV RNA viral kinetics during the treatment phase and following liver transplant and correlate results with the duration of study treatment prior to liver transplant (LT). ? To explore the presence or absence of HCV RNA in the liver explants and correlate with plasma HCV RNA viral kinetics during therapy. ? To explore the dynamics of non-tumor MELD score during the study. ? To determine concentrations of GS-7977 and metabolites in the liver explants.;Primary end point(s): The primary efficacy endpoint for subjects who receive 12 to 24 weeks of treatment during the Pre-transplant Treatment Phase and have HCV RNA < LLoQ at the last measurement prior to transplant will be the proportion of subjects with post-transplant virologic response (pTVR, defined as HCV RNA < LLoQ at Week 12 after transplant). The primary pre-transplant safety endpoint will be proportion of subjects discontinued for an adverse event; and the primary post-transplant safety endpoint will be proportion of subjects with graft loss/death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 12 weeks after stopping drug;Secondary end point(s): Subjects who receive 24 weeks of treatment and complete 12 weeks of off-treatment follow up prior to transplant will be evaluated for sustained virologic response (SVR, defined as HCV RNA < LLoQ 12 weeks after stopping study drug). The proportion of subjects who meet criteria for virologic failure, and the proportion of subjects with HCV RNA < LLoQ will be summarized over time for the pre-transplant phase. If applicable, HCV RNA absolute values (log10 IU/mL) and change from baseline for the pretransplant period will be summarized. Subjects who receive a liver transplant will be censored at the time of transplant for pre-transplant endpoints. The proportion of subjects with HCV RNA < LLoQ will be summarized over time for the post-transplant phase. | — |
Countries
New Zealand, Spain, United States
Contacts
Public ContactMedical Monitor
Gilead Sciences Inc.
Outcome results
None listed