Hepatitis C Viral Infection
Conditions
Keywords
Liver transplant, Genotype 1 HCV infection, Sofosbuvir (SOF)/ Ledipasvir (LDV), Sustained virological response (SVR12 )
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.
Interventions
DRUGSofosbuvir (SOF) and Ledipasvir (LDV)
Sponsors
University Health Network, Toronto
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response (SVR12) | 12 weeks after cessation of treatment | Defined as HCV RNA in serum below lower limit of quantification (LLOQ) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response (SVR24) | 24 weeks after cessation of treatment | Defined as HCV RNA in serum below lower limit of quantification (LLOQ) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Virological Relapse | 12 weeks after cessation of treatment or 24 weeks after cessation of treatment (becoming quantifiable again at 12 (relapse 12) or 24 (relapse 24) weeks after cessation of treatment, respectively) | Defined as HCV RNA in serum below lower limit of quantification (LLOQ) |
Countries
Canada
Outcome results
None listed