Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination ± Ribavirin in Cirrhotic Subjects With Chronic Genotype 1 HCV Infection
Condition: HCV Infection
MeSH terms: Infections; Communicable Diseases; Hepatitis C
Intervention: LDV/SOF; RBV; Placebo to match LDV/SOF; Placebo to match RBV
Intervention description: LDV/SOF (90/400 mg) FDC tablet administered orally once daily; RBV (200 mg tablets) administered orally in a divided daily dose based on weight (1000 mg per day for participants weighing < 75 kg; 1200 mg per day for participants weighing ≥ 75 kg); Placebo to match LDV/SOF administered orally once daily; Placebo to match RBV 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 155.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatitis C; HCV; Cirrhosis

Summary:

      This study is to determine the antiviral efficacy of sofosbuvir (SOF)/ledipasvir (LDV)
      fixed-dose combination (FDC) with and without ribavirin (RBV), and to evaluate the safety and
      tolerability of each regimen as assessed by review of the accumulated safety data.
      Approximately 150 participants with genotype 1 HCV infection, who have previously received
      treatment for HCV, and who have a diagnosis for cirrhosis will be enrolled. Participants will
      be randomized to 1 of 2 groups.

      Group 1: SOF/LDV FDC tablet plus placebo to match RBV for 24 weeks

      Group 2: Delayed treatment group: placebo to match SOF/LDV FDC plus placebo to match RBV for
      12 weeks, followed by SOF/LDV FDC once daily plus RBV in a divided daily dose for 12 weeks

      Randomization will 1:1 to the two groups and will be stratified by HCV genotype (1a, 1b;
      mixed or other genotype 1 results will be stratified as genotype 1a), and prior HCV therapy
      treatment response (never achieved HCV RNA < the lower limit of quantitation (LLOQ), or
      achieved HCV RNA < LLOQ).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age equal to or greater than 18 years, with chronic genotype 1 HCV infection

          -  HCV RNA ≥ 10,000 IU/mL at screening

          -  Prior virological failure after treatment with pegylated interferon (PEG-IFN), RBV and
             a protease inhibitor following documented prior virology failure after treatment with
             a PEG-IFN + RBV regimen

          -  Evidence of cirrhosis

          -  Screening laboratory values within defined thresholds

          -  Use of two effective contraception methods if female of childbearing potential or
             sexually active male

        Exclusion Criteria:

          -  Pregnant or nursing female or male with pregnant female partner

          -  Current or prior history of clinical hepatic decompensation

          -  Prior exposure to approved or experimental HCV specific direct-acting antivirals other
             than a nonstructural protein (NS)3/4A protease inhibitor

          -  History of solid organ transplantation, including liver transplant

          -  Hepatocellular carcinoma or other malignancy (with exception of certain resolved skin
             cancers)

          -  Chronic use of systemic immunosuppressive agents

          -  History of clinically significant illness or any other medical disorder that may
             interfere with subject treatment, assessment or compliance with the protocol