NCT02478229

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Jun 2015

Shorter than P25 for phase_3

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2015

Completed
4 days until next milestone

First Submitted

Initial submission to the registry

June 5, 2015

Completed
18 days until next milestone

First Posted

Study publicly available on registry

June 23, 2015

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2016

Completed
Last Updated

August 8, 2016

Status Verified

August 1, 2016

Enrollment Period

10 months

First QC Date

June 5, 2015

Last Update Submit

August 4, 2016

Conditions

Hepatitis C Viral Infection

Keywords

Liver transplantGenotype 1 HCV infectionSofosbuvir (SOF)/ Ledipasvir (LDV)Sustained virological response (SVR12 )

Outcome Measures

Primary Outcomes (1)

  • Sustained Virological Response (SVR12)

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

    12 weeks after cessation of treatment

Secondary Outcomes (1)

  • Sustained Virological Response (SVR24)

    24 weeks after cessation of treatment

Other Outcomes (1)

  • 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)

Study Arms (1)

SOF and LDV

EXPERIMENTAL

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.

Drug: Sofosbuvir (SOF) and Ledipasvir (LDV)

Interventions

Sofosbuvir (SOF) and Ledipasvir (LDV)DRUG
SOF and LDV

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2N2, Canada

Location

Related 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.

    PMID: 24725238BACKGROUND

  • 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.

    PMID: 21506241BACKGROUND

  • 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.

    PMID: 23281974BACKGROUND

  • 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.

    PMID: 23982366BACKGROUND

  • 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.

    PMID: 19935376BACKGROUND

  • 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.

    PMID: 24428467BACKGROUND

  • 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.

    PMID: 23516677BACKGROUND

  • 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.

    PMID: 23061767BACKGROUND

MeSH Terms

Interventions

Sofosbuvirledipasvir

Intervention Hierarchy (Ancestors)

Uridine MonophosphateUracil NucleotidesPyrimidine NucleotidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleotidesNucleic Acids, Nucleotides, and NucleosidesRibonucleotides

Study Officials

  • Eberhard Renner, M.D.

    University Health Network, Toronto

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 5, 2015

First Posted

June 23, 2015

Study Start

June 1, 2015

Primary Completion

April 1, 2016

Study Completion

August 1, 2016

Last Updated

August 8, 2016

Record last verified: 2016-08

Locations

CA(1)