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

NCT04682509 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 20-01386
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

ESRD

Outcome Measures

Primary Outcomes (1)

• 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.

  Visit 2 (Day 1) , Visit 3 (Day 3) , Visit 4 (Day 7), Visit 5 (Day 13), Visit 16 (Day 365)

Secondary Outcomes (8)

• Percentage of Overall patient and graft survival at 1 year post-transplant

  Visit 1 (Day 0), Visit 16 (Day 365)

• Change in the Allograft function

  Visit 1 (Day 0), Visit 16 (Day 365)

• Percentage of Incidence and grade of biopsy-proven rejection

  Visit 1 (Day 0), Visit 16 (Day 365)

• Time course to transplantation (median)

  Screening vist, Visit 1 (Day 0)

• Percentage of Incidence HCV viremia post-transplant and after 2 weeks of treatment

  Visit 1 (Day 0), Visit 5 (Day 13), Visit 16 (Day 365)

Study Arms (1)

Study group

EXPERIMENTAL

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.

Drug: Glecaprevir/pibrentasvir

Interventions

Glecaprevir/pibrentasvir DRUG

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).

Also known as: Mavyret

Study group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

glecaprevir and pibrentasvir

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bonnie Lonze, MD, PhD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: December 23, 2020
• Study Start: March 20, 2022
• Primary Completion: May 16, 2023
• Study Completion: February 28, 2024
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)