LIVE-C-Free: Early and Late Treatment of Hepatitis C With Sofosbuvir/Ledipasvir in Liver Transplant Recipients

The predominant remaining questions for post-transplant treatment of Hepatitis C virus (HCV) in the DAA (direct acting anti-virals) era are whether a ribavirin-free regimen is possible and whether pre-emptive treatment is now a potential option to prevent long-term damage to the allograft.

Our aim is to provide answers to these primary questions with our multicenter, prospective, randomized, open-label intent-to-treat phase IV study

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Sofosbuvir/Ledipasvir x 12 weeks; Drug: Sofosbuvir/Ledipasvir + Ribavirin x 12 weeks

Detailed Description

This is a multicenter, prospective, randomized, open-label phase IV study.

Compare ledipasvir/sofosbuvir + ribavirin for 12 weeks vs ledipasvir/sofosbuvir alone for 12 weeks in patients over 90 days post-liver transplant

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • MedStar Georgetown University Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. At least 18 years of age and able to give informed consent
2. History of HCV genotype 1 or 4
3. Normal EKG
4. At least 91 days post orthotopic liver transplant
5. Screening laboratory values within defined thresholds
6. Detectable HCV RNA at screening
7. Creatinine Clearance of at least 40ml/min using the Cockcroft Gault equation
8. Negative pregnancy test for female subjects within 48 hours prior to receiving study medication
9. Use of two effective contraception methods if female of childbearing potential or sexually active male unless status post bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or vasectomy

Exclusion Criteria

1. Serious or active medical or psychiatric illness
2. History of significant or unstable cardiac disease
3. Stomach disorder that could interfere with the absorption of the study drug
4. Pregnant or nursing females or males with a pregnant female partner
5. Co-infected with Hepatits B (HBV) or HIV
6. Recipients of an allograft from a donor that was infected with HCV with an unknown genotype or non-genotype 1 or 4 unless the recipient is demonstrated to have only genotype 1 or 4 HCV replication post-transplant
7. Allergic to or intolerant of sofosbuvir, ledipasvir, or ribavirin
8. History of exposure to an Nonstructural protein (NS5A) inhibitor
9. Within 1 year of transplant AND history of Hepatocellular Carcinoma (HCC) with tumor burden outside of the Milan Criteria (See Appendix II) prior to transplant
10. Participated in a clinical study with an investigational drug or biologic within the last 30 days
11. Combined liver/kidney transplant
12. History of organ transplant other than liver
13. Childs Turcotte Pugh (CTP) B or C
14. Patients with fibrosing cholestatic hepatitis
15. Platelet count of ≤ 30 k/mm3
16. Hemoglobin < 10g/dL
17. Total bilirubin > 10mg/dL
18. Alanine aminotransferase (ALT),aspartate aminotransferase (AST), or alkaline phosphatase ≥ 10x upper limit normal
19. Serum sodium < 125mmol/L
20. Current use of any of the Prohibited Interventions (Section 5.3.2) and un-willing to discontinue use, or use of amiodarone within 6 months of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Late Cohort, Arm 1; Ledispasvir (LDV) and Sofosbuvir (SOF) monotherapy x 12 weeks	Drug: Sofosbuvir/Ledipasvir x 12 weeks; Other Names: Harvoni
Active Comparator: Late Cohort, Arm 2; Ledispasvir (LDV) and Sofosbuvir (SOF) +ribavirin x 12 weeks	Drug: Sofosbuvir/Ledipasvir + Ribavirin x 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Efficacy	Treatment efficacy, defined as the percentage of patients achieving sustained virologic response 12 (SVR12) weeks after completing the antiviral regimen	12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Virologic Failure	Number of participants who had a nonresponse to treatment or a relapse of disease under study.	12 weeks
Hemoglobin Levels	Change in hemoglobin levels over the course of the study	Week 4, Week 8, Week 12, Week 16

Collaborators and Investigators

• Sponsor: Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): May 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimate): December 16, 2015

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Sofosbuvir; Ribavirin; Ledipasvir
• Other Study ID Numbers: IN-US-337-1830