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

Study Overview
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Brief Summary
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The predominant remaining questions for post-transplant treatment of Hepatitis C virus (HCV) in the DAA (direct acting anti-virals) era are whether a ribavirin-free regimen is possible and whether pre-emptive treatment is now a potential option to prevent long-term damage to the allograft. Our aim is to provide answers to these primary questions with our multicenter, prospective, randomized, open-label intent-to-treat phase IV study

Detailed Description
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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

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

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Sofosbuvir/Ledipasvir x 12 weeks
* Drug: Sofosbuvir/Ledipasvir + Ribavirin x 12 weeks


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Late Cohort, Arm 1<br>Ledispasvir (LDV) and Sofosbuvir (SOF) monotherapy x 12 weeks | Drug: Sofosbuvir/Ledipasvir x 12 weeks<br> <br> * Other names: Harvoni;|
| Active Comparator: Late Cohort, Arm 2<br>Ledispasvir (LDV) and Sofosbuvir (SOF) +ribavirin x 12 weeks | Drug: Sofosbuvir/Ledipasvir + Ribavirin x 12 weeks<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Efficacy | Treatment efficacy, defined as the percentage of patients achieving sustained virologic response 12 (SVR12) weeks after completing the antiviral regimen | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Virologic Failure | Number of participants who had a nonresponse to treatment or a relapse of disease under study. | 12 weeks | 
| Hemoglobin Levels | Change in hemoglobin levels over the course of the study | Week 4, Week 8, Week 12, Week 16 |