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

Phase 3
Terminated
Conditions
Hepatitis C Viral Infection
Interventions
Registration Number
NCT02478229
Lead Sponsor
University Health Network, Toronto
Brief Summary

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

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
1
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SOF and LDVSofosbuvir (SOF) and Ledipasvir (LDV)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.
Primary Outcome Measures
NameTimeMethod
Sustained Virological Response (SVR12)12 weeks after cessation of treatment

Defined as HCV RNA in serum below lower limit of quantification (LLOQ)

Secondary Outcome Measures
NameTimeMethod
Sustained Virological Response (SVR24)24 weeks after cessation of treatment

Defined as HCV RNA in serum below lower limit of quantification (LLOQ)

Trial Locations

Locations (1)

University Health Network

🇨🇦

Toronto, Ontario, Canada

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