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

Hepatitis C Viral Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02478229
• Other study ID #: 15-8883-A
• Status: Terminated
• Phase: Phase 3
• First received: June 5, 2015
• Last updated: August 4, 2016
• Start date: June 2015
• Est. completion date: August 2016

Study information

• Verified date: August 2016
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: August 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C
• Hepatitis C Viral Infection
• Recurrence
• Virus Diseases

Intervention

Drug:
• Sofosbuvir (SOF) and Ledipasvir (LDV)

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

References & Publications (8)

Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11. — View Citation

Bzowej N, Nelson DR, Terrault NA, Everson GT, Teng LL, Prabhakar A, Charlton MR; PHOENIX Study Group. PHOENIX: A randomized controlled trial of peginterferon alfa-2a plus ribavirin as a prophylactic treatment after liver transplantation for hepatitis C virus. Liver Transpl. 2011 May;17(5):528-38. doi: 10.1002/lt.22271. — View Citation

Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Symonds WT, Hindes RG, Berrey MM. Nucleotide polymerase inhibitor sofosbuvir plus ribavirin for hepatitis C. N Engl J Med. 2013 Jan 3;368(1):34-44. doi: 10.1056/NEJMoa1208953. — View Citation

Osinusi A, Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, Sneller M, Kohli A, Barrett L, Proschan M, Herrmann E, Shivakumar B, Gu W, Kwan R, Teferi G, Talwani R, Silk R, Kotb C, Wroblewski S, Fishbein D, Dewar R, Highbarger H, Zhang X, Kleiner D, Wood BJ, Chavez J, Symonds WT, Subramanian M, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S. Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial. JAMA. 2013 Aug 28;310(8):804-11. doi: 10.1001/jama.2013.109309. Erratum in: JAMA. 2013 Nov 13;310(18):1987. Dosage error in article text. — View 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. — View 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. Erratum in: N Engl J Med. 2014 Apr 10;370(15):1469. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Virological Relapse	Defined as HCV RNA in serum below lower limit of quantification (LLOQ)	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)	No
Primary	Sustained Virological Response (SVR12)	Defined as HCV RNA in serum below lower limit of quantification (LLOQ)	12 weeks after cessation of treatment	No
Secondary	Sustained Virological Response (SVR24)	Defined as HCV RNA in serum below lower limit of quantification (LLOQ)	24 weeks after cessation of treatment	No