A Single-center Pilot Study Evaluating a Preemptive Short Course of Glecaprevir/Pibrentasvir in Hepatitis C Positive to Negative Kidney Transplantation

A Single-center Pilot Study Evaluating a Preemptive Short Course of Glecaprevir/Pibrentasvir in Hepatitis C Positive to Negative Kidney Transplantation

The purpose of this research study is to evaluate the feasibility of a 2 week course of glecaprevir/pibrentasvir (Mavyret) starting immediately prior to transplantation to treat hepatitis C virus (HCV) in kidney transplant recipients who receive a kidney from a donor with HCV.

This is a prospective, open-label, single-center, pilot study. The patient population will include 20 patients who are on the kidney transplant waitlist at NYU Langone Health, are hepatitis C virus (HCV) negative, are willing to accept an organ from an HCV positive donor, and consent to participate in this trial. Study subjects will receive a kidney transplant from a deceased donor who tested positive for HCV as confirmed by nucleic acid amplification testing (NAT) per standard of care. All study subjects will receive a two week course of preemptive therapy with glecaprevir/pibrentasvir (Mavyret®), starting on postoperative day (POD) 0 prior to the transplant. If HCV RNA is undetectable after 2 weeks of therapy, Mavyret will be discontinued and study subjects will be followed with an intensive HCV monitoring protocol. If HCV RNA is detectable after 2 weeks of therapy, Mavyret will be continued to complete a full course of 8 weeks per standard of care. All patients will undergo close monitoring and surveillance for HCV viremia post-transplant to ensure that sustained virologic response (SVR) is achieved.

Inclusion Criteria:

• At least 18 years of age
• Listed for kidney transplantation at NYU Langone Health and willing to accept HCV positive donor organs
• Able to complete routine post-transplant visits and study visits for a minimum of 1 year after transplantation
• Women of childbearing potential must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Stategy (REMS) after transplant due to increased risk of birth defects and/or miscarriage
• Both men and women must agree to use at least one barrier method of contraception after transplant to prevent any secretion exchange
• Able and willing to provide informed consent
• Receive an organ offer for a kidney from a deceased donor that:
• Is HCV NAT positive
• Meets all standard criteria for organ acceptability at NYU Langone Transplant Institute

Exclusion Criteria:

• HCV RNA positive or history of previously treated HCV
• Evidence of active hepatitis B infection or on active antiviral treatment of HBV
• HIV positivity
• Pregnant or nursing (lactacting) women
• Current use of atazanavir or rifampin
• Known hypersensitivity to glecaprevir and/or pibrentasvir
• Current or history of decompensated liver disease
• Recipients of dual organs (i.e. simultaneous liver and kidney transplant, simultaneous kidney and pancreas transplant, or simultaneous heart and kidney transplant)
• Receive an organ offer for a kidney from a deceased donor that is:
• Confirmed HIV positive
• Confirmed HBV positive (positive hepatitis B surface antigen, and/or detectable hepatitis B virus DNA)
• Known to have previously failed DAA therapy for treatment for HCV
• HCV antibody positive, but NAT negative