Ledipasvir/Sofosbuvir Fixed-Dose Combination Plus Ribavirin in Participants With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant
Condition: Chronic HCV Infection
MeSH terms: Hepatitis C; Liver Diseases
Intervention: LDV/SOF; RBV
Intervention description: LDV/SOF FDC tablet administered orally once daily; RBV tablets administered orally in a divided daily dose
Intervention MeSH terms: Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 334.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.