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Trial record 1 of 13 for:    gs-7977 transplant
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Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01559844
Recruitment Status : Completed
First Posted : March 21, 2012
Results First Posted : May 28, 2015
Last Update Posted : July 27, 2016
Information provided by (Responsible Party):
Gilead Sciences

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.

Condition or disease Intervention/treatment Phase
Hepatitis C Hepatocellular Carcinoma Drug: Sofosbuvir Drug: Ribavirin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 61 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : March 2012
Actual Primary Completion Date : May 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: SOF+RBV
Sofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first.
Drug: Sofosbuvir
Sofosbuvir 400 mg (2 x 200 mg tablets) administered orally once daily
Other Names:
  • GS-7977
  • PSI-7977
  • Sovaldi®

Drug: Ribavirin
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)

Primary Outcome Measures :
  1. 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.

  2. 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 ]
  3. Percentage of Participants With Graft Loss Following Transplant [ Time Frame: Up to 48 weeks following transplant ]
  4. 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 Outcome Measures :
  1. Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48 [ Time Frame: Up to 48 weeks following transplant ]
    pTVR was defined as HCV RNA < the lower limit of quantification (LLOQ, ie, 25 mL/IU) at the relevant time point after transplant.

  2. Percentage of Participants With HCV RNA < LLOQ (ie, 25 mL/IU) During Treatment Through Week 48 [ Time Frame: Up to 48 weeks prior to transplant ]
  3. HCV RNA and Change From Baseline in HCV RNA Through Week 8 [ Time Frame: Up to 8 weeks prior to transplant ]
  4. Proportion of Participants With Virologic Failure Prior to Transplant [ Time Frame: Up to 48 weeks prior to transplant ]

    Virologic failure (VF) in the pretransplant phase was defined by:

    • Breakthrough (HCV RNA ≥ 25 IU/ml after having previously had HCV RNA < 25 IU/ml, while on treatment)
    • Rebound (breakthrough or > 1 log10 IU/ml increase in HCV RNA from nadir while on treatment)
    • Non-response (HCV RNA ≥ 25 IU/ml through 8 weeks of treatment)
    • Pre-transplant relapse (HCV RNA ≥ 25 IU/ml during the Pre-Transplant off-treatment follow-up period after having achieved HCV RNA < 25 IU/ml at last observed HCV RNA on treatment)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Willing and able to provide written informed consent
  2. Males or females, age > 18 years old
  3. 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.
  4. 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)
  5. HCV RNA > 10^4 IU/mL at screening
  6. 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.
  7. Child-Pugh Score (CPT) ≤ 7
  8. Planned management of the subject to meet United Network for Organ Sharing (UNOS) criteria, with imaging studies made available for review if required.
  9. Has not been treated with any investigational drug or device within 30 days of the screening visit.

Exclusion Criteria:

  1. Females of child-bearing potential who is pregnant or nursing
  2. Prior exposure to a direct-acting antiviral targeting the HCV nonstructural (NS)5B polymerase
  3. Any transplant patient who has agreed to a liver transplant from a live donor.
  4. 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
  5. Current, uncontrolled ascites, variceal hemorrhage, hepatic encephalopathy, hepatorenal syndrome and hepatopulmonary syndrome, among other signs of decompensated cirrhosis.
  6. Chronic liver disease of a non-HCV etiology (eg, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis)
  7. Infection with hepatitis B virus (HBV) or HIV
  8. Contraindications to RBV therapy
  9. Chronic use of systemically administered immunosuppressive agents (eg, prednisone equivalent > 10 mg/day) in the pretransplant treatment period.
  10. History of previous solid organ transplantation
  11. Evidence of renal impairment (CLcr < 60 mL/min) calculated by the Cockcroft-Gault equation.
  12. History or current evidence of psychiatric illness, immunologic disorder, hemoglobinopathy, pulmonary or cardiac disease, porphyria, or poorly controlled diabetes, cancer other than HCC, or a history of malignancy that in the opinion of the investigator makes the patient unsuitable for the study. Patients with clinical signs or symptoms of acute pancreatitis with elevated lipase (at Screening or during the screening period)
  13. Known hypersensitivity to RBV, the study investigational medicinal product, the metabolites, or formulation excipients
  14. History of having received any systemic antineoplastic (including sorafenib) or immunomodulatory treatment (including radiation) within 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study (excluding a local regional therapy such as TACE).
  15. Treatment with Transcatheter arterial chemoembolization (TACE) or radio frequency ablation (RFA) within 30 days prior to the first dose.
  16. Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to first dose administration at the baseline/Day 1 Visit.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01559844

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United States, California
UCLA Medical Center-The Pfleger Liver Institute
Los Angeles, California, United States, 90095
UC San Diego
San Diego, California, United States, 92103
University of California, San Francisco
San Francisco, California, United States, 94143-0124
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80010
United States, Florida
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
University of Miami
Miami, Florida, United States, 33102-5405
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Lahey Clinic Medical Center
Burlington, Massachusetts, United States, 01805
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Missouri
St. Louis University Hospital
St. Louis, Missouri, United States, 63110-0250
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Pennsylvania
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
Baylor Health Care System
Dallas, Texas, United States, 75246
New Zealand
Auckland Clinical Studies
Auckland, New Zealand
Liver Unit Clinica University de Navara
Pamplona, Spain, 31008
Sponsors and Collaborators
Gilead Sciences
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Study Director: Jill Denning, MA Gilead Sciences
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Gilead Sciences Identifier: NCT01559844    
Other Study ID Numbers: P7977-2025
First Posted: March 21, 2012    Key Record Dates
Results First Posted: May 28, 2015
Last Update Posted: July 27, 2016
Last Verified: June 2016
Keywords provided by Gilead Sciences:
hepatocellular carcinoma
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Disease Attributes
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents