Ledipasvir/Sofosbuvir Fixed-Dose Combination Plus Ribavirin in Participants With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant

A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir/Ledipasvir Fixed-Dose Combination + Ribavirin Administered in Subjects Infected With Chronic HCV Who Have Advanced Liver Disease or Are Post-Liver Transplant

This study will evaluate ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) in participants with advanced liver disease or posttransplant and chronic genotype 1 or 4 hepatitis C virus (HCV) infection.

• Cohort A: decompensated cirrhosis (advanced liver disease), no prior liver transplant;
• Cohort B: post-liver transplant, with or without cirrhosis;
• Group assignment within cohorts is based on severity of liver impairment at screening (Child-Pugh-Turcotte (CPT) score for participants with cirrhosis; fibrosis; or presence of disease for fibrosing cholestatic hepatitis (FCH) groups)
• Randomization is 1:1 within groups to 12 or 24 weeks of LDV/SOF+RBV treatment.

Inclusion Criteria:

• Able to provide written informed consent
• Chronic genotype 1 and/or 4 HCV infection
• Normal ECG
• Negative serum pregnancy test for female subjects
• Male subjects and female subjects of childbearing potential must agree to use contraception
• Able to comply with the dosing instructions for study drug and able to complete the study schedule of assessments, including all required post treatment visits

Exclusion Criteria:

• Serious or active medical or psychiatric illness
• HIV or hepatitis B viral (HBV) infection
• Stomach disorder that could interfere with the absorption of the study drug
• Treated with an anti-HCV medication in the last 30 days
• Any prior exposure to an HCV nonstructural protein (NS)5a-specific inhibitor
• Use of human granulocyte-macrophage colony-stimulating factor (GM-CSF), epoetin alfa or other therapeutic hematopoietic agents within 2 weeks of screening
• History of clinically significant medical condition associated with other chronic liver disease
• Active spontaneous bacterial peritonitis at screening
• Females who are breastfeeding
• Infection requiring systemic antibiotics
• Participated in a clinical study with an investigational drug or biologic within the last 30 days
• Active or history (last 6 months) of drug or alcohol abuse
• History of organ transplant other than liver, kidney, or corneal.