Clinical trial NCT02478229: Early Treatment With Sofosbuvir (SOF) and Ledipasvir (LDV) to Prevent HCV Recurrence After Liver Transplantation (OLT)
Official title: Early Treatment With Sofosbuvir (SOF) and Ledipasvir (LDV) to Prevent HCV Recurrence After Liver Transplantation (OLT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatitis C Viral Infection
Keywords: Liver transplant
Genotype 1 HCV infection
Sofosbuvir (SOF)/ Ledipasvir (LDV)
Sustained virological response (SVR12 )
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2015-06-23
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sustained Virological Response (SVR12)
timeFrame: 12 weeks after cessation of treatment
Secondary outcomes:
measure: Sustained Virological Response (SVR24)
timeFrame: 24 weeks after cessation of treatment
Other outcomes:
measure: Virological Relapse
timeFrame: 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)
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Eberhard Renner, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Selzner N, Renner EL, Selzner M, Adeyi O, Kashfi A, Therapondos G, Girgrah N, Herath C, Levy GA, Lilly L. Antiviral treatment of recurrent hepatitis C after liver transplantation: predictors of response and long-term outcome. Transplantation. 2009 Nov 27;88(10):1214-21. doi: 10.1097/TP.0b013e3181bd783c.
citation: Sulkowski MS, Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, Jacobson I, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, Everson GT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D, Hindes R, Symonds W, Pasquinelli C, Grasela DM; AI444040 Study Group. Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection. N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218.
citation: Tanaka T, Therapondos G, Selzner N, Renner EL, Lilly LB. Serum aspartate aminotransferase levels and previous histopathological findings enable reduction of protocol liver biopsies after liver transplantation for hepatitis C. Can J Gastroenterol. 2013 Mar;27(3):131-6. doi: 10.1155/2013/904636.
citation: Tanaka T, Benmousa A, Marquez M, Therapondos G, Renner EL, Lilly LB. The long-term efficacy of nucleos(t)ide analog plus a year of low-dose HBIG to prevent HBV recurrence post-liver transplantation. Clin Transplant. 2012 Sep-Oct;26(5):E561-9. doi: 10.1111/ctr.12022.