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The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients

Primary Purpose

Kidney Transplantation, 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 Kidney Transplantation

Eligibility Criteria

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

Inclusion criteria (recipients):

Patients with end-stage renal disease listed for kidney transplantation at UPMC.
On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min
Age ≥ 18
No available living kidney donor
Listed for an isolated kidney transplant at UPMC with <60m of accrued transplant waiting time and/or <60m of dialysis time
Have panel reactive antibody level of <98%
No obvious contraindication to kidney transplant
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 other than being on hemodialysis. 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 liver cirrhosis
Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months
History of atrial fibrillation requiring the use of amiodarone over the past 12m
Patients with etiology of renal failure with increased risk of causing early graft failure as assessed by the investigator team
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
Kidney donor profile index (KDPI) score <85

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

Kidney 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).

Starting post-operative day 1, kidney 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 patients 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 graft loss

All-cause mortality

Waitlist time after enrollment

Full Information

NCT ID

NCT03809533

First Posted

January 15, 2019

Last Updated

July 18, 2023

Sponsor

Amit D Tevar, MD

Collaborators

University of Pittsburgh Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03809533

Brief Title

The Use of Hepatitis C Positive Kidneys in Hepatitis C Negative Kidney Transplant Recipients

Official Title

Transplantation of Kidneys 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

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

May 29, 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

Amit D Tevar, 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 kidneys from hepatitis C seropositive non-viremic (HCV Ab+/NAT-) and HCV seropositive viremic (HCV Ab+/NAT+) donors to HCV seronegative recipients on the kidney 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 kidneys of HCVAb+ donors to HCVAb- recipients with subsequent therapy with sofosbuvir/velpatasvir (Epclusa®). Recipients of a kidney from HCVAb+/NAT- donors will be in arm 1 (the transmission-triggered arm) of the study. In this arm, the study will monitor HCV by measuring HCV RNA in renal 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 kidney 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 renal 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

Kidney Transplantation, 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

30 (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 patients 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

Time Frame

5 years

Title

Incidence of allograft rejection

Time Frame

5 years

Title

Incidence of graft loss

Time Frame

5 years

Title

All-cause mortality

Time Frame

5 years

Title

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 renal disease listed for kidney transplantation at UPMC. On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min Age ≥ 18 No available living kidney donor Listed for an isolated kidney transplant at UPMC with <60m of accrued transplant waiting time and/or <60m of dialysis time Have panel reactive antibody level of <98% No obvious contraindication to kidney transplant 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 other than being on hemodialysis. 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 liver cirrhosis Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months History of atrial fibrillation requiring the use of amiodarone over the past 12m Patients with etiology of renal failure with increased risk of causing early graft failure as assessed by the investigator team 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 Kidney donor profile index (KDPI) score <85 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

Amit Tevar, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Fernanda Silviera, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Study Director

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 Kidneys in Hepatitis C Negative Kidney Transplant Recipients

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