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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01687257
First received: September 12, 2012
Last updated: June 14, 2016
Last verified: June 2016
  Purpose
This study will evaluate the antiviral efficacy of combination therapy with sofosbuvir (SOF) plus ribavirin (RBV) for 48 weeks in adults with compensated and decompensated chronic hepatitis C virus (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: SOF
Drug: RBV
Phase 2

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:
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation) ] [ Designated as safety issue: No ]
    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) at 12 weeks after stopping study treatment. For the Observation/SOF+RBV group, SVR12 during the observational period was defined as HCV RNA < LLOQ for 12 consecutive weeks, any time during the observational period.


Secondary Outcome Measures:
  • Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48) [ Time Frame: Posttreatment Weeks 4, 24, and 48 ] [ Designated as safety issue: No ]
    SVR4, SVR24, and SVR48 were defined as HCV RNA < LLOQ at 4, 24, and 48 weeks after stopping study treatment, respectively.

  • Percentage of Participants Experiencing On-Treatment Virologic Failure [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]

    On-treatment virologic failure was defined as:

    • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
    • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
    • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)

  • Percentage of Participants Experiencing Viral Relapse [ Time Frame: Up to Posttreatment Week 24 ] [ Designated as safety issue: No ]
    Viral relapse was defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement.

  • Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment [ Time Frame: Baseline; Week 24 (Observation) and Week 48 (SOF+RBV) ] [ Designated as safety issue: No ]
    HVPG closely reflects the degree of portal hypertension in patients with cirrhosis. The end of treatment for the Observation group was defined as the end of the observation period. The treatment period for Group 2 was defined as the end of the observation period to the end of the treatment. Baseline values were the last available values on or prior to first dose date of any study drug.

  • Change From Baseline in Child-Pugh-Turcotte (CPT) Score [ Time Frame: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV) ] [ Designated as safety issue: No ]

    CPT scores, widely used to grade the severity of cirrhosis and to determine the need for liver transplantation, are calculated based on a combination of laboratory values and clinical features. CPT scores can range from 5 to 15, with higher scores indicating a greater severity of disease. Data are presented as improvement, no change, or worsening in CPT scores at Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV groups).

    Improvement in CPT score was defined as having a decrease in CPT score from baseline, no change in CPT score was defined as having no change in CPT score from baseline, and worsening in CPT score was defined as having an increase in CPT score from baseline.

    Baseline values were the last available values on or prior to first dose date of any study drug.


  • Change From Baseline in Model for End Stage Liver Disease (MELD) Scores [ Time Frame: Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV) ] [ Designated as safety issue: No ]

    MELD scores, used to assess prognosis and suitability for transplant, are calculated based on laboratory values only and can range from 6 to 40, with higher scores indicating greater disease severity. Data are presented as improvement, no change, or worsening in MELD scores at Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV groups).

    Improvement in MELD score was defined as having a baseline MELD score of 11-15 or 16-20 that changed to 0-10, or a baseline MELD score of 16-20 that changed to 11-15; no change in MELD score was defined as having no change in score group (0-10, 11-15, or 16-20) from baseline; and worsening in MELD score was defined as having a baseline MELD score of 0-10 that changed to 11-15 or 16-20, or a baseline MELD score of 11-15 that changed to 16-20.

    Baseline values were the last available values on or prior to first dose date of any study drug.



Enrollment: 50
Study Start Date: July 2012
Study Completion Date: October 2015
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SOF+RBV
Participants will receive SOF+RBV for 48 weeks.
Drug: SOF
SOF 400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
Drug: RBV
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 SOF+RBV
Participants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks.
Drug: SOF
SOF 400 mg tablet administered orally once daily
Other Names:
  • Sovaldi®
  • GS-7977
Drug: RBV
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   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic infection with Hepatitis C with HCV RNA > 1000 IU/mL
  • Individuals 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/m^2
  • 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: Shampa De-Oertel, PhD Gilead Sciences
  More Information

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
Results First Received: January 27, 2016
Last Updated: June 14, 2016
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
New Zealand: Medsafe
Australia: Department of Health and Ageing Therapeutic Goods Administration

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

ClinicalTrials.gov processed this record on July 26, 2016