An Open-Label Study to Explore the Clinical Efficacy of Sofosbuvir With Ribavirin Administered Pre-Transplant in Preventing Hepatitis C Virus (HCV) Recurrence Post-Transplant

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01559844
First received: March 5, 2012
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

The primary objective is to determine if the administration of a combination of sofosbuvir (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.


Condition Intervention Phase
Hepatitis C
Hepatocellular Carcinoma
Drug: Sofosbuvir
Drug: Ribavirin
Phase 2

An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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:
  • Proportion of participants with post-transplant virologic response (pTVR) [ Time Frame: Up to 12 weeks post-transplantation ] [ Designated as safety issue: No ]
    Post-transplant virologic response (pTVR) is defined as HCV RNA < the lower limit of quantification (LLOQ) at Week 12 after transplant.

  • For the pre-transplant phase, proportion of participants who discontinued study due to an adverse event [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
  • For the post-transplant phase, proportion of participants with graft loss/death [ Time Frame: Up to 48 weeks post-transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of participants with virologic failure [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: No ]

    Virologic failure in the pre-transplant 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)

  • Proportion of participants with HCV RNA < LLOQ by visit on treatment and during post-treatment follow-up for the pre-transplant phase [ Time Frame: Up to 72 weeks ] [ Designated as safety issue: No ]
    The proportion of participants by visit with HCV RNA < LLOQ will be summarized for the pre-transplant phase.

  • HCV RNA (log10 IU/mL) and change from baseline in HCV RNA (log10 IU/mL) for the pre-transplant phase [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
    The HCV RNA (log10 IU/mL) and change from baseline in HCV RNA (log10 IU/mL) will be summarized by visit.

  • Proportion of participants with HCV RNA < LLOQ by visit for the post-transplant phase [ Time Frame: Up to 48 weeks post-transplant ] [ Designated as safety issue: No ]
    The proportion of participants by visit with HCV RNA < LLOQ will be summarized for the post-transplant phase.


Estimated Enrollment: 50
Study Start Date: March 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sofosbuvir + Ribavirin 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. Male subjects 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:

    • a 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
    • a 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 > 10e4 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. Subject has not been treated with any investigational drug or device within 30 days of the Screening visit.

Exclusion Criteria:

  1. A female 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. Subjects requiring planned induction therapy with biologics post-transplantation or with a post-transplantation immunosuppressive regimen not consistent with the following within the first 12 weeks post-transplant:

    • 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 post-transplant
  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 (e.g., hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, cholangitis)
  7. Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
  8. Contraindications to RBV therapy
  9. Chronic use of systemically administered immunosuppressive agents (e.g., prednisone equivalent > 10 mg/day) in the Pre-transplant 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

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01559844     History of Changes
Other Study ID Numbers: P7977-2025
Study First Received: March 5, 2012
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 28, 2014