Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01687257
First received: September 12, 2012
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

This study will evaluate the antiviral efficacy of combination therapy with sofosbuvir+ribavirin for 48 weeks in adults with compensated and decompensated chronic HCV infection. Approximately 50 adults will be randomized (1:1) to receive study drug for 48 weeks or take part in an untreated observational arm for the first 24 weeks followed by study drug for another 48 weeks.


Condition Intervention Phase
Hepatitis C
Cirrhosis
Portal Hypertension
With or Without Liver Decompensation
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: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Open-Label, Randomized Study to Investigate the Safety and Efficacy of GS-7977 and Ribavirin Administered for 48 Weeks in Patients Infected With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Week 12 ] [ Designated as safety issue: No ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.


Secondary Outcome Measures:
  • Change in Hepatic Venous Pressure Gradient (HVPG) measurements [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
  • Change in Child-Pugh-Turcotte (CPT) score [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
  • Change in Model for End-Stage Liver Disease (MELD) score [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
  • Proportion of participants with sustained virologic response at 4, 24, and 48 weeks after discontinuation of therapy (SVR4, SVR24, SVR48) [ Time Frame: Posttreatment Weeks 4, 24, and 48 ] [ Designated as safety issue: No ]
    SVR4, SVR24, SVR48 are defined as HCV RNA < LLOQ 4, 24, and 48 weeks following the last dose of study drug, respectively.

  • Proportion of participants experiencing viral breakthrough [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
    Viral breakthrough is defined as having HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (note, second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values.

  • Proportion of participants experiencing viral relapse [ Time Frame: Week 48 to Posttreatment Week 48 ] [ Designated as safety issue: No ]
    Viral relapse is defined as HCV RNA ≥ LLOQ during the posttreatment period after having achieved HCV RNA < LLOQ at end of treatment.


Enrollment: 50
Study Start Date: December 2012
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sofosbuvir+ribavirin
Participants will receive sofosbuvir plus ribavirin for 48 weeks.
Drug: Sofosbuvir
Sofosbuvir 400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
Drug: Ribavirin
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: Observation, then sofosbuvir+ribavirin
Participants will undergo 24 weeks of observation and then receive sofosbuvir plus ribavirin for 48 additional weeks.
Drug: Sofosbuvir
Sofosbuvir 400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
  • PSI-7977
Drug: Ribavirin
Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 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:

  • Chronic infection with Hepatitis C with HCV RNA > 1000 IU/mL
  • Subjects with cirrhosis with Child-Pugh score < 10.
  • esophageal or gastric varices on endoscopy within 6 months prior to or at screening
  • Hepatic Venous Pressure Gradient (HVPG) > 6 mmHg
  • Body mass index (BMI) >/= 18 kg/m2
  • Naïve to all nucleotides/nucleoside treatments for chronic HCV infection

Exclusion Criteria:

  • Have any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment, or compliance
  • HIV or chronic hepatitis B virus (HBV) infection (HBsAg positive)
  • Alpha-fetoprotein (AFP) > 50 unless negative imaging for hepatic masses within the last 6 months or during screening
  • Refractory ascites as defined by requiring paracentesis > twice within 1 month prior to screening
  • Active variceal bleeding within 6 months of screening
  • Expected survival of < 1 year
  • History of hepatorenal, or hepatopulmonary syndrome.
  • Evidence of renal impairment (CrCl < 50 mL/min)
  • History of major organ transplantation, including liver transplant.
  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: NCT01687257

Locations
United States, Colorado
Aurora, Colorado, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
Australia, New South Wales
Newtown, New South Wales, Australia
France
Leclerc, Clichy, France
New Zealand
Grafton, Auckland, New Zealand
Spain
Majadahonda, Madrid, Spain
Barcelona, Spain
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Jill M. Denning, MA Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01687257     History of Changes
Other Study ID Numbers: GS-US-334-0125, 2012-002457-29
Study First Received: September 12, 2012
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis C
Hypertension
Hypertension, Portal
Liver Cirrhosis
Liver Failure
Cardiovascular Diseases
Digestive System Diseases
Flaviviridae Infections
Hepatic Insufficiency
Hepatitis
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Vascular Diseases
Virus Diseases
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014