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

Hepatitis C Clinical Trial

Official title:

Transplantation of Kidneys 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: NCT03809533
• Other study ID #: STUDY19100135
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 29, 2019
• Est. completion date: May 1, 2024

Study information

• Verified date: July 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 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: May 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria (recipients):

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

2. On chronic hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease (CKD) defined as a glomerular filtration rate < 15 ml/min

3. Age = 18

4. No available living kidney donor

5. Listed for an isolated kidney transplant at UPMC with <60m of accrued transplant waiting time and/or <60m of dialysis time

6. Have panel reactive antibody level of <98%

7. No obvious contraindication to kidney transplant

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

9. Able to provide informed consent

10. 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 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.

4. Hepatitis B surface antigen positive

5. History of liver cirrhosis

6. Persistently elevated liver transaminases, defined as ALT/AST at least 3 times the upper limit of normal for a minimum of 3 consecutive months

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

8. Patients with etiology of renal failure with increased risk of causing early graft failure as assessed by the investigator team

9. Receipt of prior organ transplant

10. Waitlisted for a multi-organ transplant

11. Pregnant women

12. Known allergy to sofosbuvir/velpatasvir

13. 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

3. Kidney donor profile index (KDPI) score <85

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
• Kidney Transplantation

Intervention

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

Locations

Country	Name	City	State
United States	UPMC	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Amit D Tevar, 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 patients 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		5 years
Secondary	Incidence of allograft rejection		5 years
Secondary	Incidence of graft loss		5 years
Secondary	All-cause mortality		5 years
Secondary	Waitlist time after enrollment		5 years