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

1. At least 18 years of age and able to give informed consent

2. History of HCV genotype 1 or 4

3. Normal EKG

4. At least 91 days post orthotopic liver transplant

5. Screening laboratory values within defined thresholds

6. Detectable HCV RNA at screening

7. Creatinine Clearance of at least 40ml/min using the Cockroft Gault equa-tion

8. Negative pregnancy test for female subjects within 48 hours prior to re-ceiving study
medication

9. Use of two effective contraception methods if female of childbearing po-tential or
sexually active male unless status post bilateral tubal ligatation, bilateral
oophorectomy, hysterectomy, or vasectomy

Exclusion Criteria

1. Serious or active medical or psychiatric illness

2. History of significant or unstable cardiac disease

3. Stomach disorder that could interfere with the absorption of the study drug

4. Pregnant or nursing females or males with a pregnant female partner

5. Co-infected with HBV or HIV

6. 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

7. Allergic to or intolerant of sofosbuvir, ledipasvir, or ribavirin

8. History of exposure to an NS5A inhibitor

9. 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

10. Participated in a clinical study with an investigational drug or biologic within the
last 30 days

11. Combined liver/kidney transplant

12. History of organ transplant other than liver

13. Childs Turcotte Pugh (CTP) B or C

14. Patients with fibrosing cholestatic hepatitis

15. Platelet count of ≤ 30 k/mm3

16. Hemoglobin < 10g/dL

17. Total bilirubin > 10mg/dL

18. ALT, AST, or alkaline phosphatase ≥ 10x ULN

19. Serum sodium < 125mmol/L

20. 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