Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01559844
First received: March 5, 2012
Last updated: June 2, 2015
Last verified: June 2015
  Purpose

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 subjects with hepatocellular carcinoma (HCC) meeting the MILAN criteria prior to undergoing liver transplantation for up to 24 weeks can 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 Intervention Phase
Hepatitis C
Hepatocellular Carcinoma
Drug: Sofosbuvir
Drug: Ribavirin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12 [ Time Frame: Posttransplant Week 12 ] [ Designated as safety issue: No ]
    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 Sobosbuvir Prior to Receiving Transplant [ Time Frame: Up to 48 weeks prior to transplant ] [ Designated as safety issue: No ]
  • Percentage of Participants With Graft Loss Following Transplant [ Time Frame: Up to 48 weeks following transplant ] [ Designated as safety issue: No ]
  • Number of Participants Who Died [ Time Frame: Up to 48 weeks following transplant ] [ Designated as safety issue: No ]
    • Treatment-emergent deaths were those that occurred while taking study drug or within 30 days after stopping study drug.
    • Only those participants who underwent liver transplantation were analyzed for death post-transplantation.


Secondary Outcome Measures:
  • Percentage of Participants With Posttransplant Virologic Response (pTVR) Through Posttransplant Week 48 [ Time Frame: Up to 48 weeks following transplant ] [ Designated as safety issue: No ]
    pTVR was defined as HCV RNA < the lower limit of quantification (LLOQ, ie, 25 mL/IU) at the relevant time point after transplant.

  • 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 ] [ Designated as safety issue: No ]
  • HCV RNA and Change From Baseline in HCV RNA Through Week 8 [ Time Frame: Up to 8 weeks prior to transplant ] [ Designated as safety issue: No ]
  • Proportion of Participants With Virologic Failure Prior to Transplant [ Time Frame: Up to 48 weeks prior to transplant ] [ Designated as safety issue: No ]

    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)


Enrollment: 61
Study Start Date: March 2012
Study Completion Date: October 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559844

Locations
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
University of Miami
Miami, Florida, United States, 33102-5405
Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
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
Spain
Liver Unit Clinica University de Navara
Pamplona, Spain, 31008
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jill Denning, MA Gilead Sciences
  More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01559844     History of Changes
Other Study ID Numbers: P7977-2025
Study First Received: March 5, 2012
Results First Received: May 12, 2015
Last Updated: June 2, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Hepatitis
Chronic
hepatocellular carcinoma
HCC
transplant

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Hepatitis
Hepatitis A
Hepatitis C
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015