Back to resultsSofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation
Primary Purpose
Hepatitis C, Cirrhosis, Portal Hypertension
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SOF
RBV
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
SOF+RBV
Observation, then SOF+RBV
Arm Description
Participants will receive SOF+RBV for 48 weeks.
Participants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
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)
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
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
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
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01687257
Brief Title
Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C, Cirrhosis, Portal Hypertension, With or Without Liver Decompensation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SOF+RBV
Arm Type
Experimental
Arm Description
Participants will receive SOF+RBV for 48 weeks.
Arm Title
Observation, then SOF+RBV
Arm Type
Experimental
Arm Description
Participants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks.
Intervention Type
Drug
Intervention Name(s)
SOF
Other Intervention Name(s)
Sovaldi®, GS-7977
Intervention Description
SOF 400 mg tablet administered orally once daily
Intervention Type
Drug
Intervention Name(s)
RBV
Intervention Description
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)
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description
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.
Time Frame
Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48)
Description
SVR4, SVR24, and SVR48 were defined as HCV RNA < LLOQ at 4, 24, and 48 weeks after stopping study treatment, respectively.
Time Frame
Posttreatment Weeks 4, 24, and 48
Title
Percentage of Participants Experiencing On-Treatment Virologic Failure
Description
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)
Time Frame
Up to 48 weeks
Title
Percentage of Participants Experiencing Viral Relapse
Description
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.
Time Frame
Up to Posttreatment Week 24
Title
Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment
Description
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.
Time Frame
Baseline; Week 24 (Observation) and Week 48 (SOF+RBV)
Title
Change From Baseline in Child-Pugh-Turcotte (CPT) Score
Description
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.
Time Frame
Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)
Title
Change From Baseline in Model for End Stage Liver Disease (MELD) Scores
Description
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.
Time Frame
Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shampa De-Oertel, PhD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Aurora
State/Province
Colorado
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
Philadelphia
State/Province
Pennsylvania
Country
United States
City
Newtown
State/Province
New South Wales
Country
Australia
City
Leclerc
State/Province
Clichy
Country
France
City
Grafton
State/Province
Auckland
Country
New Zealand
City
Majadahonda
State/Province
Madrid
Country
Spain
City
Barcelona
Country
Spain
12. IPD Sharing Statement
Learn more about this trial
Sofosbuvir and Ribavirin in Patients With Chronic HCV With Cirrhosis and Portal Hypertension With or Without Liver Decompensation
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