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

Primary Purpose

Hepatitis C Viral Infection

Status
Terminated
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Sofosbuvir (SOF) and Ledipasvir (LDV)
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C Viral Infection focused on measuring Liver transplant, Genotype 1 HCV infection, Sofosbuvir (SOF)/ Ledipasvir (LDV), Sustained virological response (SVR12 )

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SOF and LDV

Arm Description

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.

Outcomes

Primary Outcome Measures

Sustained Virological Response (SVR12)
Defined as HCV RNA in serum below lower limit of quantification (LLOQ)

Secondary Outcome Measures

Sustained Virological Response (SVR24)
Defined as HCV RNA in serum below lower limit of quantification (LLOQ)

Full Information

First Posted
June 5, 2015
Last Updated
August 4, 2016
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT02478229
Brief Title
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

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Terminated
Why Stopped
difficulty recruiting patients
Study Start Date
June 2015 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Viral Infection
Keywords
Liver transplant, Genotype 1 HCV infection, Sofosbuvir (SOF)/ Ledipasvir (LDV), Sustained virological response (SVR12 )

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SOF and LDV
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir (SOF) and Ledipasvir (LDV)
Primary Outcome Measure Information:
Title
Sustained Virological Response (SVR12)
Description
Defined as HCV RNA in serum below lower limit of quantification (LLOQ)
Time Frame
12 weeks after cessation of treatment
Secondary Outcome Measure Information:
Title
Sustained Virological Response (SVR24)
Description
Defined as HCV RNA in serum below lower limit of quantification (LLOQ)
Time Frame
24 weeks after cessation of treatment
Other Pre-specified Outcome Measures:
Title
Virological Relapse
Description
Defined as HCV RNA in serum below lower limit of quantification (LLOQ)
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eberhard Renner, M.D.
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
24725238
Citation
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.
Results Reference
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PubMed Identifier
21506241
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.
Results Reference
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PubMed Identifier
23281974
Citation
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Results Reference
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PubMed Identifier
23982366
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.
Results Reference
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PubMed Identifier
19935376
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.
Results Reference
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24428467
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.
Results Reference
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PubMed Identifier
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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.
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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.
Results Reference
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Early Treatment With Sofosbuvir (SOF) and Ledipasvir (LDV) to Prevent HCV Recurrence After Liver Transplantation (OLT)

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