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: January 27, 2016
Last verified: January 2016

September 12, 2012
January 27, 2016
July 2012
January 2015   (final data collection date for primary outcome measure)
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.
Sustained virologic response 12 weeks after discontinuation of therapy. [ Time Frame: 12 weeks after discontinuation of therapy (SVR12) ] [ Designated as safety issue: No ]
Sustained virologic response 12 weeks after discontinuation of therapy (SVR12 defined as HCV RNA < lower limit of quantification [LLoQ] 12 weeks after last dose of study drug).
Complete list of historical versions of study NCT01687257 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ] [ Designated as safety issue: No ]
    SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
  • Percentage of Participants Experiencing On-Treatment Virologic Failure [ Time Frame: Up to 24 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 is 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. An HVPG measurement ≥ 10 mmHg represents clinically significant portal hypertension. A reduction in HVPG ≥ 20% or below the 12 mmHg threshold markedly reduces the risk of variceal bleeding, and varices may decrease in size. The end of treatment for the Observation group was defined as the end of the observation period.
  • 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 (All SOF+RBV).

    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.

  • 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 CPT scores at Week 24 (Observation) and Posttreatment Week 4 (All SOF+RBV).

    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

  • Change in Hepatic Venous Pressure Gradient (HVPG) measurements [ Time Frame: Baseline and after 24 weeks of treatment ] [ Designated as safety issue: No ]
    Determine the effect of 24 weeks of treatment on portal pressure as measured by Hepatic Venous Pressure Gradient (HVPG) measurements
  • Frequency and severity of adverse events [ Time Frame: Safety and Tolerability on treatment and 30 days post last dose ] [ Designated as safety issue: No ]
    Assess safety laboratory tests and the number, frequency and severity of adverse events through 30 days post last dose of study drug
Not Provided
Not Provided
 
Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hepatitis C
  • Cirrhosis
  • Portal Hypertension
  • With or Without Liver Decompensation
  • 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: SOF+RBV
    Participants will receive SOF+RBV for 48 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: Observation, then SOF+RBV
    Participants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
October 2015
January 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   France,   New Zealand,   Spain
 
NCT01687257
GS-US-334-0125, 2012-002457-29
Yes
Not Provided
Not Provided
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Shampa De-Oertel, PhD Gilead Sciences
Gilead Sciences
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP