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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01687257
• Other study ID #: GS-US-334-0125
• Secondary ID: 2012-002457-29
• Status: Completed
• Phase: Phase 2
• First received: September 12, 2012
• Last updated: January 27, 2016
• Start date: July 2012
• Est. completion date: October 2015

Study information

• Verified date: January 2016
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Spain: Agencia Española de Medicamentos y Productos SanitariosNew Zealand: MedsafeAustralia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cirrhosis
• Hepatitis C
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Liver Failure
• Portal Hypertension
• With or Without Liver Decompensation

Intervention

Drug:
• SOF
SOF 400 mg tablet administered orally once daily
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  France,  New Zealand,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Posttreatment Week 12 (SOF+RBV) and up to 24 weeks (Observation)	No
Secondary	Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)	SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.	Posttreatment Weeks 4 and 24	No
Secondary	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)	Up to 24 weeks	No
Secondary	Percentage of Participants Experiencing Viral Relapse	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.	Up to Posttreatment Week 24	No
Secondary	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. 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.	Baseline; Week 24 (Observation) and Week 48 (SOF+RBV)	No
Secondary	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 (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.	Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)	No
Secondary	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 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	Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)	No