Back to resultsA Single-center Pilot Study Evaluating a Preemptive Short Course of Glecaprevir/Pibrentasvir in Hepatitis C Positive to Negative Kidney Transplantation
Primary Purpose
ESRD
Status
Enrolling by invitation
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Glecaprevir/pibrentasvir
Sponsored by
About this trial
This is an interventional prevention trial for ESRD
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
Sites / Locations
- NYU Langone Health
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study group
Arm Description
All study subjects will receive glecaprevir/pibrentasvir (Mavyret®) 300/120 mg orally x 14 days, starting on POD 0 prior to transplantation of the HCV positive kidney. 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. Safety monitoring and frequent surveillance for HCV viremia will occur for all subjects throughout the duration of the study. The kidney transplantation procedure and routine post-transplant management will be performed per standard of care.
Outcomes
Primary Outcome Measures
Change in the Percentage of Incidence of sustained clearance of HCV (cure) 12 weeks after treatment of viremia
Measured in percentage of patients with SVR after treatment for HCV after kidney transplant. SVR will be defined as the absence of detectable HCV RNA Quantitative (PCR) testing 12 weeks after the completion of the treatment course.
Secondary Outcome Measures
Percentage of Overall patient and graft survival at 1 year post-transplant
Patients will have regular follow-up as standard-of-care for all kidney transplant recipients. Patients' survival will be readily apparent. Furthermore, all deaths of transplant recipients and allograft losses within the first year of transplant are required to be reported to UNOS. Survival rates will be reported as a percentage.
Change in the Allograft function
This parameter is being used to measure overall graft function and will be described using the median value at 1 year post transplant for the cohort. All transplant recipients will have regular follow-up as standard-of-care and eGFR will be calculated using the MDRD equation.
Percentage of Incidence and grade of biopsy-proven rejection
All transplant recipients will have regular follow-up as routine clinical care and as such, will receive for cause biopsies per standard of care if there is a clinical suspicion of rejection. Biopsies will be read by a renal pathologist per standard of care and reported in the EPIC system. The incidence of rejection will be calculated as a percentage of the patients with diagnosed rejection on biopsy within 1 year of transplant.
Time course to transplantation (median)
Time to transplantation will be measured from the time of listing (recorded in EPIC) to time of transplant and also time from written acknowledgment of willingness to participate in the trial to time of transplant.
Percentage of Incidence HCV viremia post-transplant and after 2 weeks of treatment
Measuring serial HCV RNA Quantitative (PCR) starting immediately after transplant and continued throughout the duration of the study. A patient will be considered to be viremic when a post-transplant HCV RNA Quantitative (PCR) test is positive. The incidence of viremia after transplant will be calculated as the percent of the patients transplanted with an HCV-positive donor who subsequently developed HCV viremia (detected by RNA Quantitative (PCR) testing). The incidence of viremia after two weeks of treatment will be calculated as the percentage of the patients with detectable HCV viremia (detected by RNA Quantitative (PCR) testing) after completing 2 weeks of treatment with glecaprevir/pibrentasvir and therefore require continuation of therapy to complete an 8 week course
Time course of exposure to development of clinically detectable viremia in those who develop viremia
Measuring serial HCV RNA Quantitative (PCR) starting immediately after transplant and continued throughout the duration of the study to find the median time to viremia with standard deviations. If the HCV RNA Quantitative (PCR) test is positive at any time point, we will calculate the time from transplant to detectable HCV RNA Quantitative (PCR).
Time course of clearance of viremia after treatment initiation
Measuring serial HCV RNA Quantitative (PCR) starting immediately after transplant and continued throughout the duration of the study to find the median time to clearance with standard deviations. If the HCV RNA Quantitative (PCR) test is positive at any time point, we will calculate the time to documented clearance as indicated by an undetectable HCV RNA Quantitative (PCR),
Percentage of Incidence of treatment failure/treatment resistant strains of HCV
If SVR12 is not achieved with either a 2 week or 8 week course of glecaprevir/pibrentasvir, it will be considered a treatment failure and resistance testing will be performed. The incidence will be reported as a percentage.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04682509
Brief Title
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
March 20, 2022 (Actual)
Primary Completion Date
March 1, 2024 (Anticipated)
Study Completion Date
March 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ESRD
7. Study Design
Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Study group
Arm Type
Experimental
Arm Description
All study subjects will receive glecaprevir/pibrentasvir (Mavyret®) 300/120 mg orally x 14 days, starting on POD 0 prior to transplantation of the HCV positive kidney. 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. Safety monitoring and frequent surveillance for HCV viremia will occur for all subjects throughout the duration of the study. The kidney transplantation procedure and routine post-transplant management will be performed per standard of care.
Intervention Type
Drug
Intervention Name(s)
Glecaprevir/pibrentasvir
Other Intervention Name(s)
Mavyret
Intervention Description
Manufacturer is AbbVie, Inc., North Chicago, IL Mavyret® is commercially available and FDA approved for the treatment of HCV genotype 1, 2, 3, 4, 5, or 6 infection in patients without cirrhosis or with compensated cirrhosis and also for the treatment of adult patients with HCV genotype 1 infection who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor. An immediate release bilayer oral tablet containing a fixed-dose combination of 100 mg of glecaprevir and 40 mg of pibrentasvir. The daily dose of glecaprevir/pibrentasvir used will be the standard FDA approved dose: 3 tablets taken once daily (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg).
Primary Outcome Measure Information:
Title
Change in the Percentage of Incidence of sustained clearance of HCV (cure) 12 weeks after treatment of viremia
Description
Measured in percentage of patients with SVR after treatment for HCV after kidney transplant. SVR will be defined as the absence of detectable HCV RNA Quantitative (PCR) testing 12 weeks after the completion of the treatment course.
Time Frame
Visit 2 (Day 1) , Visit 3 (Day 3) , Visit 4 (Day 7), Visit 5 (Day 13), Visit 16 (Day 365)
Secondary Outcome Measure Information:
Title
Percentage of Overall patient and graft survival at 1 year post-transplant
Description
Patients will have regular follow-up as standard-of-care for all kidney transplant recipients. Patients' survival will be readily apparent. Furthermore, all deaths of transplant recipients and allograft losses within the first year of transplant are required to be reported to UNOS. Survival rates will be reported as a percentage.
Time Frame
Visit 1 (Day 0), Visit 16 (Day 365)
Title
Change in the Allograft function
Description
This parameter is being used to measure overall graft function and will be described using the median value at 1 year post transplant for the cohort. All transplant recipients will have regular follow-up as standard-of-care and eGFR will be calculated using the MDRD equation.
Time Frame
Visit 1 (Day 0), Visit 16 (Day 365)
Title
Percentage of Incidence and grade of biopsy-proven rejection
Description
All transplant recipients will have regular follow-up as routine clinical care and as such, will receive for cause biopsies per standard of care if there is a clinical suspicion of rejection. Biopsies will be read by a renal pathologist per standard of care and reported in the EPIC system. The incidence of rejection will be calculated as a percentage of the patients with diagnosed rejection on biopsy within 1 year of transplant.
Time Frame
Visit 1 (Day 0), Visit 16 (Day 365)
Title
Time course to transplantation (median)
Description
Time to transplantation will be measured from the time of listing (recorded in EPIC) to time of transplant and also time from written acknowledgment of willingness to participate in the trial to time of transplant.
Time Frame
Screening vist, Visit 1 (Day 0)
Title
Percentage of Incidence HCV viremia post-transplant and after 2 weeks of treatment
Description
Measuring serial HCV RNA Quantitative (PCR) starting immediately after transplant and continued throughout the duration of the study. A patient will be considered to be viremic when a post-transplant HCV RNA Quantitative (PCR) test is positive. The incidence of viremia after transplant will be calculated as the percent of the patients transplanted with an HCV-positive donor who subsequently developed HCV viremia (detected by RNA Quantitative (PCR) testing). The incidence of viremia after two weeks of treatment will be calculated as the percentage of the patients with detectable HCV viremia (detected by RNA Quantitative (PCR) testing) after completing 2 weeks of treatment with glecaprevir/pibrentasvir and therefore require continuation of therapy to complete an 8 week course
Time Frame
Visit 1 (Day 0), Visit 5 (Day 13), Visit 16 (Day 365)
Title
Time course of exposure to development of clinically detectable viremia in those who develop viremia
Description
Measuring serial HCV RNA Quantitative (PCR) starting immediately after transplant and continued throughout the duration of the study to find the median time to viremia with standard deviations. If the HCV RNA Quantitative (PCR) test is positive at any time point, we will calculate the time from transplant to detectable HCV RNA Quantitative (PCR).
Time Frame
Visit 1 (Day 0) to Visit 16 (Days 364)
Title
Time course of clearance of viremia after treatment initiation
Description
Measuring serial HCV RNA Quantitative (PCR) starting immediately after transplant and continued throughout the duration of the study to find the median time to clearance with standard deviations. If the HCV RNA Quantitative (PCR) test is positive at any time point, we will calculate the time to documented clearance as indicated by an undetectable HCV RNA Quantitative (PCR),
Time Frame
Visit 1 (Day 0) to Visit 16 (Days 364)
Title
Percentage of Incidence of treatment failure/treatment resistant strains of HCV
Description
If SVR12 is not achieved with either a 2 week or 8 week course of glecaprevir/pibrentasvir, it will be considered a treatment failure and resistance testing will be performed. The incidence will be reported as a percentage.
Time Frame
Visit 1 (Day 0), Visit 5 (Day 13), Visit 9 (Day 56)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bonnie Lonze, MD, PhD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
This is a single center pilot study. Data will be available once published.
Learn more about this trial
A Single-center Pilot Study Evaluating a Preemptive Short Course of Glecaprevir/Pibrentasvir in Hepatitis C Positive to Negative Kidney Transplantation
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