The Use of Hepatitis C Positive Livers in Hepatitis C Negative Liver Transplant Recipients

Hepatitis C Clinical Trial

Official title:

Transplantation of Livers of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa®)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03819322
• Other study ID #: STUDY19100082
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 15, 2019
• Est. completion date: March 17, 2025

Study information

• Verified date: November 2023
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, pilot trial to test the safety and efficacy of transplantation of livers from Hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the liver transplant waitlist. Treatment and prophylaxis will be administered, using a transmission-triggered approach for the first scenario (HCV Ab+/NAT- donors, arm 1) and a prophylaxis approach for the later scenario (HCV Ab+/NAT+ donors, arm 2).

Description:

This is a prospective, single center, pilot, open-label study of transplantation of livers of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a liver from HCVAb+/NAT- donors will be in arm 1 (the transmission-triggered arm) of the study. In this arm, the study will monitor transmission of HCV by measuring HCV RNA in liver transplant recipients. If HCV RNA is detected, indicating transmission of HCV, recipients will be treated with sofosbuvir/velpatasvir (Epclusa®) for 12 weeks. Virological response will be assessed at 4 weeks, end of treatment and 12 weeks after completion of therapy.

Recipients of a liver from HCVAb+/NAT+ donors will be in arm 2 (the prophylaxis arm) of the study. In this arm, patients will be started on a 12-week course of sofosbuvir/velpatasvir (Epclusa®) immediately post-operatively and will undergo close monitoring of HCV RNA for evidence of transmission.

To be eligible for the study, subjects need to be listed for liver transplantation, be not infected with HCV, HBV or HIV, and sign informed consent.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 73
• Est. completion date: March 17, 2025
• Est. primary completion date: March 17, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria (recipients):

1. Patients with end-stage liver disease listed for liver transplantation at UPMC.

2. Age = 18

3. No available living liver donor

4. Listed for an isolated liver transplant at UPMC

5. Have panel reactive antibody level of <98%

6. Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation

7. Able to provide informed consent

8. Be willing to use a contraceptive method for a year after transplant

Exclusion criteria (recipients):

1. HIV positive

2. HCVAb or HCV RNA positive

3. Presence of behavioral risk factors for contracting HCV. These behavioral risk factors are current injection drug use, current intranasal illicit drug use, current percutaneous/parenteral exposures in an unregulated setting.

4. Hepatitis B surface antigen positive

5. History of atrial fibrillation requiring the use of amiodarone over the past 12m

6. Receipt of prior organ transplant

7. Waitlisted for a multi-organ transplant

8. Pregnant women

9. Known allergy to sofosbuvir/velpatasvir

10. Any condition, psychiatric or physical, that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study

Inclusion criteria (donors):

1. HCV antibody positive

2. HCV NAT negative or positive

Exclusion criteria (donors):

1. Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT)

2. Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)

3. Known ongoing therapy for HCV

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Liver Transplant

Intervention

Drug:
• sofosbuvir/velpatasvir
12 week, oral, fixed dose

Locations

Country	Name	City	State
United States	UPMC	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Naudia Jonassaint. MD	University of Pittsburgh Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in study participants in each experimental group	5 years
Primary	HCV free at 1 year	Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation	1 year
Secondary	Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients	Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients	5 years
Secondary	Incidence of allograft rejection	Incidence of allograft rejection at 5 years	5 years
Secondary	Incidence of graft loss	Incidence of graft loss at 5 years	5 years
Secondary	All-cause mortality	All-cause mortality at 5 years	5 years
Secondary	Waitlist time after enrollment	Waitlist time after enrollment	5 years