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

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ClinicalTrials.gov Identifier: NCT03809533
Recruitment Status : Not yet recruiting
First Posted : January 18, 2019
Last Update Posted : January 18, 2019
Sponsor:
Information provided by (Responsible Party):
Amit Tevar, University of Pittsburgh

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).

Condition or disease Intervention/treatment Phase
Kidney Transplantation Hepatitis C Drug: sofosbuvir/velpatasvir Phase 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Transplantation of Kidneys of Hepatitis C (HCV) Seropositive Donors to HCV Seronegative Recipients With Subsequent Therapy With Sofosbuvir/Velpatasvir (Epclusa)
Estimated Study Start Date : February 1, 2019
Estimated Primary Completion Date : February 1, 2024
Estimated Study Completion Date : February 1, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arm Intervention/treatment
Experimental: HCV seropositive non-viremic (HCV Ab+/NAT-) donor

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).

Drug: sofosbuvir/velpatasvir
12-week, oral, fixed-dose
Other Name: Epclusa

Experimental: HCV seropositive viremic (HCV Ab+/NAT+) donor
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).
Drug: sofosbuvir/velpatasvir
12-week, oral, fixed-dose
Other Name: Epclusa




Primary Outcome Measures :
  1. Adverse Events [ Time Frame: 5 years ]
    Rate of adverse events due to sofosbuvir/velpatasvir (Epclusa) in patients in each experimental group

  2. HCV free at 1 year [ Time Frame: 1 year ]
    Proportion of participants in each experimental group who are free of HCV at 1 year following transplantation


Secondary Outcome Measures :
  1. Transmission rate of HCV from HCVAb+/NAT- donors to HCVAb- recipients [ Time Frame: 5 years ]
  2. Incidence of allograft rejection [ Time Frame: 5 years ]
  3. Incidence of graft loss [ Time Frame: 5 years ]
  4. All-cause mortality [ Time Frame: 5 years ]
  5. Waitlist time after enrollment [ Time Frame: 5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 liver 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03809533


Contacts
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Contact: Study Coordinator 412-383-8616 johnsonr1@upmc.edu

Locations
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United States, Pennsylvania
UPMC
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Amit Tevar
Investigators
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Principal Investigator: Amit Tevar, MD University of Pittsburgh
Study Director: Fernanda Silviera, MD University of Pittsburgh

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Responsible Party: Amit Tevar, Associate Professor of Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03809533     History of Changes
Other Study ID Numbers: PRO18030039
First Posted: January 18, 2019    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Sofosbuvir
Velpatasvir
Sofosbuvir-velpatasvir drug combination
Antiviral Agents
Anti-Infective Agents