Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant
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
1 other identifier
interventional
61
3 countries
15
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2012
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
March 1, 2012
CompletedFirst Submitted
Initial submission to the registry
March 5, 2012
CompletedFirst Posted
Study publicly available on registry
March 21, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2014
CompletedResults Posted
Study results publicly available
May 28, 2015
CompletedJuly 27, 2016
June 1, 2016
2.2 years
March 5, 2012
May 12, 2015
June 16, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
pTVR was defined as HCV RNA \< the lower limit of quantification (LLOQ, ie, 25 mL/IU) at Week 12 after transplant.
Posttransplant Week 12
Percentage of Participants Experiencing Any Adverse Event Leading to Permanent Discontinuation of Sofosbuvir Prior to Receiving Transplant
Up to 48 weeks prior to transplant
Percentage of Participants With Graft Loss Following Transplant
Up to 48 weeks following transplant
Number of Participants Who Died
* 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.
Up to 48 weeks following transplant
Secondary Outcomes (4)
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
Study Arms (1)
SOF+RBV
EXPERIMENTALSofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first.
Interventions
Sofosbuvir 400 mg (2 x 200 mg tablets) administered orally once daily
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
Eligibility Criteria
You may qualify if:
- 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 ≥ 22.
- 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.
- Has not been treated with any investigational drug or device within 30 days of the screening visit.
You may not qualify if:
- 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)
- Infection with hepatitis B virus (HBV) or HIV
- Contraindications to RBV therapy
- Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent \> 10 mg/day) in the pretransplant treatment period.
- History of previous solid organ transplantation
- Evidence of renal impairment (CLcr \< 60 mL/min) calculated by the Cockcroft-Gault equation.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Gilead Scienceslead
Study Sites (15)
UCLA Medical Center-The Pfleger Liver Institute
Los Angeles, California, 90095, United States
UC San Diego
San Diego, California, 92103, United States
University of California, San Francisco
San Francisco, California, 94143-0124, United States
University of Colorado
Aurora, Colorado, 80010, United States
University of Miami
Miami, Florida, 33102-5405, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33140, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Lahey Clinic Medical Center
Burlington, Massachusetts, 01805, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
St. Louis University Hospital
St Louis, Missouri, 63110-0250, United States
Columbia University
New York, New York, 10032, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Baylor Health Care System
Dallas, Texas, 75246, United States
Auckland Clinical Studies
Auckland, New Zealand
Liver Unit Clinica University de Navara
Pamplona, 31008, Spain
Related Publications (2)
Babusis D, Curry MP, Kirby B, Park Y, Murakami E, Wang T, Mathias A, Afdhal N, McHutchison JG, Ray AS. Sofosbuvir and Ribavirin Liver Pharmacokinetics in Patients Infected with Hepatitis C Virus. Antimicrob Agents Chemother. 2018 Apr 26;62(5):e02587-17. doi: 10.1128/AAC.02587-17. Print 2018 May.
PMID: 29439971DERIVEDCurry MP, Forns X, Chung RT, Terrault NA, Brown R Jr, Fenkel JM, Gordon F, O'Leary J, Kuo A, Schiano T, Everson G, Schiff E, Befeler A, Gane E, Saab S, McHutchison JG, Subramanian GM, Symonds WT, Denning J, McNair L, Arterburn S, Svarovskaia E, Moonka D, Afdhal N. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015 Jan;148(1):100-107.e1. doi: 10.1053/j.gastro.2014.09.023. Epub 2014 Sep 28.
PMID: 25261839DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Disclosures
- Organization
- Gilead Sciences, Inc.
Study Officials
- STUDY DIRECTOR
Jill Denning, MA
Gilead Sciences
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 5, 2012
First Posted
March 21, 2012
Study Start
March 1, 2012
Primary Completion
May 1, 2014
Study Completion
October 1, 2014
Last Updated
July 27, 2016
Results First Posted
May 28, 2015
Record last verified: 2016-06