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

NCT ID: NCT01559844

Last Updated: 2016-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2014-10-31

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.

Conditions

Hepatitis C; Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SOF+RBV

Sofosbuvir plus ribavirin for up to 48 weeks or until time of transplant, whichever occurs first.

Group Type: EXPERIMENTAL

Sofosbuvir

Intervention Type: DRUG

Sofosbuvir 400 mg (2 x 200 mg tablets) administered orally once daily

Ribavirin

Intervention Type: DRUG

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)

Interventions

Sofosbuvir

Sofosbuvir 400 mg (2 x 200 mg tablets) administered orally once daily

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

GS-7977; PSI-7977; Sovaldi®

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jill Denning, MA

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

UCLA Medical Center-The Pfleger Liver Institute

Los Angeles, California, United States

UC San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

University of Miami

Miami, Florida, United States

Mount Sinai Medical Center

Miami Beach, Florida, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Lahey Clinic Medical Center

Burlington, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

St. Louis University Hospital

St Louis, Missouri, United States

Columbia University

New York, New York, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Baylor Health Care System

Dallas, Texas, United States

Auckland Clinical Studies

Auckland, , New Zealand

Liver Unit Clinica University de Navara

Pamplona, , Spain

Countries

United States; New Zealand; Spain

References

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.

Reference Type: DERIVED

PMID: 29439971 (View on PubMed)

Curry 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.

Reference Type: DERIVED

PMID: 25261839 (View on PubMed)

Other Identifiers

P7977-2025

Identifier Type: -

Identifier Source: org_study_id