Clinical trial NCT03809533: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Kidney Transplantation
Hepatitis C
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of Pittsburgh Medical Center
First posted: 2019-01-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse Events
timeFrame: 5 years
measure: HCV free at 1 year
timeFrame: 1 year
Secondary outcomes:
measure: Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients
timeFrame: 5 years
measure: Incidence of allograft rejection
timeFrame: 5 years
measure: Incidence of graft loss
timeFrame: 5 years
measure: All-cause mortality
timeFrame: 5 years
measure: Waitlist time after enrollment
timeFrame: 5 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Amit Tevar, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Fernanda Silviera, MD
role: STUDY_DIRECTOR
References: