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

NCT01687257 | Completed Phase 2 Results DMC

• 2 other identifiers: GS-US-334-01252012-002457-29
• Study Type: interventional
• Target: 50
• Locations: 5 countries
• Sites: 9

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.

Conditions

Hepatitis C; Cirrhosis; Portal Hypertension; With or Without Liver Decompensation

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (6)

• Percentage of Participants With SVR at 4, 24, and 48 Weeks After Discontinuation of Therapy (SVR4, SVR24, and SVR48)

  Posttreatment Weeks 4, 24, and 48

• Percentage of Participants Experiencing On-Treatment Virologic Failure

  Up to 48 weeks

• Percentage of Participants Experiencing Viral Relapse

  Up to Posttreatment Week 24

• Change From Baseline in Hepatic Venous Pressure Gradient (HVPG) at End of Treatment

  Baseline; Week 24 (Observation) and Week 48 (SOF+RBV)

• Change From Baseline in Child-Pugh-Turcotte (CPT) Score

  Baseline; Week 24 (Observation) and Posttreatment Week 4 (SOF+RBV)

Study Arms (2)

SOF+RBV

EXPERIMENTAL

Participants will receive SOF+RBV for 48 weeks.

Drug: SOF; Drug: RBV

Observation, then SOF+RBV

EXPERIMENTAL

Participants will undergo 24 weeks of observation and then receive SOF+RBV for 48 additional weeks.

Drug: SOF; Drug: RBV

Interventions

SOF DRUG

SOF 400 mg tablet administered orally once daily

Also known as: Sovaldi®, GS-7977

Observation, then SOF+RBV; SOF+RBV

RBV DRUG

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)

Observation, then SOF+RBV; SOF+RBV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (9)

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Rochester, Minnesota, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Newtown, New South Wales, Australia

Location

Unknown Facility

Leclerc, Clichy, France

Location

Unknown Facility

Grafton, Auckland, New Zealand

Location

Unknown Facility

Barcelona, Barcelona, Spain

Location

Unknown Facility

Majadahonda, Madrid, Spain

Location

MeSH Terms

Conditions

Hepatitis C; Fibrosis; Hypertension, Portal

Interventions

Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Shampa De-Oertel, PhD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2012
• First Posted: September 18, 2012
• Study Start: July 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: October 1, 2015
• Last Updated: September 16, 2016
• Results First Posted: February 24, 2016

Record last verified: 2016-08

Locations

FR (1); AU (1); US (4); ES (2); NZ (1)