Early Treatment With Sofosbuvir (SOF) and Ledipasvir (LDV) to Prevent HCV Recurrence After Liver Transplantation (OLT)

Study Overview
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Brief Summary
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The study is a single centre, single arm, open-label, proof of concept study enrolling 20 adult primary liver transplant recipients with genotype 1 HCV infection. Subjects will receive Sofosbuvir (SOF) and Ledipasvir (LDV) starting at time of liver transplantation (OLT) and continues for 12 weeks. Subjects will be receive 24 week post-treatment follow up.

Detailed Description
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Hepatitis C viral infection (HCV) leading to end-stage liver disease is the leading indication for liver transplant worldwide. HCV recurrence following liver transplantation is universal, associated with 100-fold increase in viremia levels, and runs at an accelerated course, leading to graft cirrhosis in up to 30% of patients within 5 years. Successful eradication of HCV post transplant normalizes the long term survival of HCV positive liver transplant recipients. This study aims to treat HCV infection starting at the time of transplant. The study is a single centre, single arm, open-label,proof of concept study enrolling 20 adult primary liver transplant recipients with genotype 1 HCV infection. Subjects will receive Sofosbuvir (SOF) 400 mg and Ledipasvir (LDV) 90 mg as a fixed dose combination (FDC) tablet starting at time of liver transplantation (OLT) and continues for 12 weeks. Subjects will receive 24 week post-treatment follow up. The study will investigate if the patient has achieved sustained virological response (SVR) 12 weeks after cessation of treatment (SVR12). Furthermore, safety and efficacy of this treatment regimen beginning at the time of transplant will be investigated.

Official Title
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Early Treatment With Sofosbuvir (SOF) and Ledipasvir (LDV) to Prevent HCV Recurrence After Liver Transplantation (OLT)

Conditions
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Hepatitis C Viral Infection

Intervention / Treatment
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* Drug: Sofosbuvir (SOF) and Ledipasvir (LDV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient of a first (primary) live or deceased (after brain or cardiac death) donor liver transplant Willing and able to provide written informed consent Male or Female, age 18-70 years old Medical MELD score ≤30 at time of transplant (calculated based on serum bilirubin, creatinine and INR, i.e. not taking exception points into account) Quantifiable HCV RNA at time of listing or transplant evaluation HCV genotype 1a or 1b infection Female patients must have a negative pregnancy test at enrolment Exclusion Criteria: Liver re-transplantation Recipients of multiple solid organ transplants Estimated GFR <30ml/min at time of transplant Participants transplanted for fulminant hepatic failure Participants co-infected with HBV or HIV Previous treatment with a Sofosbuvir or Ledipasvir containing regimen Participation in an interventional clinical trial within 1 month prior to enrolment Known allergies or hypersensitivity to Sofosbuvir or Ledipasvir Pregnancy and/or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF and LDV<br>Single arm: All participants will be started on Sofosbuvir (SOF) 400 mg and Ledipasvir (LDV) 90 mg as a fixed dose combination (FDC) tablet p.o. once daily with or without food starting at the time of liver transplantation (OLT), i.e. first doses given immediately prior to OLT, and continuing for 12 weeks. | Drug: Sofosbuvir (SOF) and Ledipasvir (LDV)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (SVR12) | Defined as HCV RNA in serum below lower limit of quantification (LLOQ) | 12 weeks after cessation of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (SVR24) | Defined as HCV RNA in serum below lower limit of quantification (LLOQ) | 24 weeks after cessation of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplant, Genotype 1 HCV infection, Sofosbuvir (SOF)/ Ledipasvir (LDV), Sustained virological response (SVR12 )