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

Primary Purpose

Liver Transplant, Hepatitis C

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

sofosbuvir/velpatasvir

About this trial

This is an interventional treatment trial for Liver Transplant

Eligibility Criteria

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

Inclusion criteria (recipients):

Patients with end-stage liver disease listed for liver transplantation at UPMC.
Age ≥ 18
No available living liver donor
Listed for an isolated liver transplant at UPMC
Have panel reactive antibody level of <98%
Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation
Able to provide informed consent
Be willing to use a contraceptive method for a year after transplant

Exclusion criteria (recipients):

HIV positive
HCVAb or HCV RNA positive
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.
Hepatitis B surface antigen positive
History of atrial fibrillation requiring the use of amiodarone over the past 12m
Receipt of prior organ transplant
Waitlisted for a multi-organ transplant
Pregnant women
Known allergy to sofosbuvir/velpatasvir
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):

HCV antibody positive
HCV NAT negative or positive

Exclusion criteria (donors):

Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT)
Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT)
Known ongoing therapy for HCV

Sites / Locations

UPMC

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

HCV seropositive non-viremic (HCV Ab+/NAT-) donor

HCV seropositive viremic (HCV Ab+/NAT+) donor

Arm Description

Liver recipients will be monitored for HCV for one year following transplant. When HCV RNA is detected, the transmission-triggered treatment phase will be initiated. Recipients will be treated with 12-week oral course of sofosbuvir/velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).

Post-operative day 1, liver recipients will be treated with 12-week oral course of sofosbuvir/ velpatasvir (Epclusa®), a fixed-dose combination of a nucleotide analogue HCV NS5B polymerase inhibitor (sofosbuvir - 400mg) and a NS5A inhibitor (velpatasvir - 100mg).

Outcomes

Primary Outcome Measures

Adverse events

Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in study participants in each experimental group

HCV free at 1 year

Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation

Secondary Outcome Measures

Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients

Incidence of allograft rejection

Incidence of allograft rejection at 5 years

Incidence of graft loss

Incidence of graft loss at 5 years

All-cause mortality

All-cause mortality at 5 years

Waitlist time after enrollment

Full Information

NCT ID

NCT03819322

First Posted

January 24, 2019

Last Updated

October 6, 2022

Sponsor

Naudia Jonassaint. MD

Collaborators

University of Pittsburgh Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03819322

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 15, 2019 (Actual)

Primary Completion Date

May 1, 2024 (Anticipated)

Study Completion Date

May 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Naudia Jonassaint. MD

Collaborators

University of Pittsburgh Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief 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).

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Transplant, Hepatitis C

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

73 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HCV seropositive non-viremic (HCV Ab+/NAT-) donor

Arm Type

Experimental

Arm Description

Arm Title

HCV seropositive viremic (HCV Ab+/NAT+) donor

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

sofosbuvir/velpatasvir

Other Intervention Name(s)

Epclusa

Intervention Description

12 week, oral, fixed dose

Primary Outcome Measure Information:

Title

Adverse events

Description

Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in study participants in each experimental group

Time Frame

5 years

Title

HCV free at 1 year

Description

Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients

Description

Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients

Time Frame

5 years

Title

Incidence of allograft rejection

Description

Incidence of allograft rejection at 5 years

Time Frame

5 years

Title

Incidence of graft loss

Description

Incidence of graft loss at 5 years

Time Frame

5 years

Title

All-cause mortality

Description

All-cause mortality at 5 years

Time Frame

5 years

Title

Waitlist time after enrollment

Description

Waitlist time after enrollment

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria (recipients): Patients with end-stage liver disease listed for liver transplantation at UPMC. Age ≥ 18 No available living liver donor Listed for an isolated liver transplant at UPMC Have panel reactive antibody level of <98% Able to travel to UPMC for routine post-transplant visits and study visits for a minimum of 12 months after transplantation Able to provide informed consent Be willing to use a contraceptive method for a year after transplant Exclusion criteria (recipients): HIV positive HCVAb or HCV RNA positive 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. Hepatitis B surface antigen positive History of atrial fibrillation requiring the use of amiodarone over the past 12m Receipt of prior organ transplant Waitlisted for a multi-organ transplant Pregnant women Known allergy to sofosbuvir/velpatasvir 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): HCV antibody positive HCV NAT negative or positive Exclusion criteria (donors): Confirmed HIV positive (positive HIV-1 antibody, positive HIV-2 antibody, positive p24 antigen and/or positive HIV NAT) Confirmed HBV positive (positive hepatitis B surface antigen and/or HBV NAT) Known ongoing therapy for HCV

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fernanda Silviera, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Naudia Jonassaint, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

UPMC

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

We do not plan to share individual patient data outside of our investigative team. Aggregate data will be shared in publications as appropriate.

Learn more about this trial

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

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