Clinical trial NCT04682509: A Single-center Pilot Study Evaluating a Preemptive Short Course of Glecaprevir/Pibrentasvir in Hepatitis C Positive to Negative Kidney Transplantation
Official title: A Single-center Pilot Study Evaluating a Preemptive Short Course of Glecaprevir/Pibrentasvir in Hepatitis C Positive to Negative Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: ESRD
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2020-12-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in the Percentage of Incidence of sustained clearance of HCV (cure) 12 weeks after treatment of viremia
timeFrame: Visit 2 (Day 1) , Visit 3 (Day 3) , Visit 4 (Day 7), Visit 5 (Day 13), Visit 16 (Day 365)
Secondary outcomes:
measure: Percentage of Overall patient and graft survival at 1 year post-transplant
timeFrame: Visit 1 (Day 0), Visit 16 (Day 365)
measure: Change in the Allograft function
timeFrame: Visit 1 (Day 0), Visit 16 (Day 365)
measure: Percentage of Incidence and grade of biopsy-proven rejection
timeFrame: Visit 1 (Day 0), Visit 16 (Day 365)
measure: Time course to transplantation (median)
timeFrame: Screening vist, Visit 1 (Day 0)
measure: Percentage of Incidence HCV viremia post-transplant and after 2 weeks of treatment
timeFrame: Visit 1 (Day 0), Visit 5 (Day 13), Visit 16 (Day 365)
measure: Time course of exposure to development of clinically detectable viremia in those who develop viremia
timeFrame: Visit 1 (Day 0) to Visit 16 (Days 364)
measure: Time course of clearance of viremia after treatment initiation
timeFrame: Visit 1 (Day 0) to Visit 16 (Days 364)
measure: Percentage of Incidence of treatment failure/treatment resistant strains of HCV
timeFrame: Visit 1 (Day 0), Visit 5 (Day 13), Visit 9 (Day 56)
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Bonnie Lonze, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: