Evaluate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination and Ribavirin for 12 Weeks in Participants With Chronic HCV Infection and Child-Pugh-Turcotte Class C Cirrhosis
Condition: Hepatitis C Virus Infection
MeSH terms: Infections; Communicable Diseases; Hepatitis C
Intervention: SOF/VEL; RBV
Intervention description: 400/100 mg FDC tablet administered orally once daily; Tablets administered orally at 600 mg, if well tolerated then up to a maximum total daily dose of 1000 to 1200 mg (based on weight) divided twice daily.
Intervention MeSH terms: Sofosbuvir; Sofosbuvir-velpatasvir drug combination; Velpatasvir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objectives of this study are to evaluate the efficacy, safety, and tolerability
      of the treatment with sofosbuvir velpatasvir (SOF/VEL) fixed-dose combination (FDC) with
      ribavirin (RBV) for 12 weeks in participants with chronic hepatitis C virus (HCV) infection
      and Child-Pugh-Turcotte (CPT) Class C cirrhosis.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  A body mass index (BMI) of ≥ 18 kg/m^2

          -  Chronic HCV infection (≥ 6 months) as documented by either prior medical history or
             liver biopsy

          -  Quantifiable HCV RNA at screening

          -  Individuals may be non-transplanted or with recurrent HCV post-liver transplant.

               -  If listed for liver transplant, then the projected date of transplant must be ≥12
                  weeks after Day1 of treatment

               -  If post-liver transplant, then Day1 must be ≥ 6 months from date of transplant

          -  CPT score of 10 to 12, inclusive, as determined at screening

          -  Liver imaging within 6 months of Day 1 to exclude hepatocellular carcinoma (HCC)

          -  If treatment-experienced, the most recent HCV treatment must have been completed at
             least 8 weeks prior to Screening

          -  Females of childbearing potential must have a negative serum pregnancy test at
             screening and a negative urine pregnancy test on Day 1 prior to randomization

          -  Males and females of childbearing potential who engage in heterosexual intercourse
             must agree to use protocol specified method(s) of contraception

          -  Females must agree to refrain from egg donation and in vitro fertilization during
             treatment until at least 30 days after the last dose of SOF/VEL or 6 months after the
             last dose of RBV, whichever occurs last

          -  Lactating females must agree to discontinue nursing before the study drugs are
             administered

          -  Males must agree to refrain from sperm donation from the date of screening until at
             least 7 months after the last dose of RBV or 30 days after the last dose of SOF/VEL,
             whichever occurs last

          -  Adults must be able to comply with the dosing instructions for study drug
             administration and able to complete the study schedule of assessments

        Key Exclusion Criteria:

          -  Current or prior history of any of the following:

               -  Clinically significant medical or psychiatric illness or individual is currently
                  under evaluation for a potentially clinically significant illness

               -  Gastrointestinal disorder or post-operative condition that could interfere with
                  the absorption of the study drug

               -  Difficulty with blood collection and/or poor venous access for the purposes of
                  phlebotomy

               -  Significant pulmonary disease, significant cardiac disease or porphyria

               -  Malignancy within the 5 years prior to screening, with the exception of specific
                  cancers that have been cured by surgical resection (basal cell skin cancer,
                  etc.). Adults under evaluation for possible malignancy are not eligible

               -  Significant drug allergy (such as anaphylaxis or hepatotoxicity)

          -  Any history of organ transplant other than liver or kidney

          -  Chronic liver disease of a non-HCV etiology

          -  Inability to exclude HCC by imaging within 6 months of Day 1

          -  Alpha-fetoprotein (AFP) > 50 unless negative imaging for hepatic masses within the
             last 6 months or during screening

          -  Active spontaneous bacterial peritonitis at screening

          -  Infection requiring systemic antibiotics at the time of screening

          -  Evidence of fibrosing cholestatic hepatitis at screening

          -  Life threatening serious adverse event (SAE) during screening

          -  Active variceal bleeding within 6 months of screening

          -  Prior placement of a portosystemic shunt (such as TIPS)

          -  ECG with clinically significant abnormalities

          -  Laboratory parameters with clinically significant abnormalities

          -  Hepatitis B surface antigen positive at screening

          -  Infection with human immunodeficiency virus (HIV)

          -  Clinically-relevant alcohol or drug abuse within 12 months of screening. A positive
             drug screen will exclude individuals unless it can be explained by a prescribed
             medication; the diagnosis and prescription must be approved by the Investigator

          -  Prior exposure to any HCV Non-structural Protein 5A (NS5A) inhibitor

          -  Current use of corticosteroids at any dose >10 mg of prednisone/day (or equivalent
             dose of corticosteroid)

          -  Use of any prohibited concomitant medications

          -  Use of granulocyte macrophage colony-stimulating factor (GM-CSF), epoetin alfa or
             other hematopoietic stimulating agents within 2 weeks of screening

          -  Male with pregnant female partner

          -  History of clinically significant hemoglobinopathy (eg, sickle cell disease,
             thalassemia)

          -  Contraindications to RBV therapy

          -  Known hypersensitivity to VEL, RBV, SOF, the metabolites, or formulation excipients

          -  Participation in a clinical study with an investigational drug or biologic within 3
             months prior to Day 1

        NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.