LIVE-C-Free: Early and Late Treatment of Hepatitis C With Sofosbuvir/Ledipasvir in Liver Transplant Recipients

This is a multicenter, prospective, randomized, open-label phase IV study.

Compare ledipasvir/sofosbuvir + ribavirin for 12 weeks vs ledipasvir/sofosbuvir alone for 12 weeks in patients over 90 days post-liver transplant

Inclusion criteria

• At least 18 years of age and able to give informed consent
• History of HCV genotype 1 or 4
• Normal EKG
• At least 91 days post orthotopic liver transplant
• Screening laboratory values within defined thresholds
• Detectable HCV RNA at screening
• Creatinine Clearance of at least 40ml/min using the Cockcroft Gault equation
• Negative pregnancy test for female subjects within 48 hours prior to receiving study medication
• Use of two effective contraception methods if female of childbearing potential or sexually active male unless status post bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or vasectomy

Exclusion criteria

• Serious or active medical or psychiatric illness
• History of significant or unstable cardiac disease
• Stomach disorder that could interfere with the absorption of the study drug
• Pregnant or nursing females or males with a pregnant female partner
• Co-infected with Hepatits B (HBV) or HIV
• Recipients of an allograft from a donor that was infected with HCV with an unknown genotype or non-genotype 1 or 4 unless the recipient is demonstrated to have only genotype 1 or 4 HCV replication post-transplant
• Allergic to or intolerant of sofosbuvir, ledipasvir, or ribavirin
• History of exposure to an Nonstructural protein (NS5A) inhibitor
• Within 1 year of transplant AND history of Hepatocellular Carcinoma (HCC) with tumor burden outside of the Milan Criteria (See Appendix II) prior to transplant
• Participated in a clinical study with an investigational drug or biologic within the last 30 days
• Combined liver/kidney transplant
• History of organ transplant other than liver
• Childs Turcotte Pugh (CTP) B or C
• Patients with fibrosing cholestatic hepatitis
• Platelet count of ≤ 30 k/mm3
• Hemoglobin < 10g/dL
• Total bilirubin > 10mg/dL
• Alanine aminotransferase (ALT),aspartate aminotransferase (AST), or alkaline phosphatase ≥ 10x upper limit normal
• Serum sodium < 125mmol/L
• Current use of any of the Prohibited Interventions (Section 5.3.2) and un-willing to discontinue use, or use of amiodarone within 6 months of screening