Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant

Pan-genotypic Direct Acting Antiviral Therapy in Donor HCV-positive to Recipient HCV-negative Kidney Transplant

This is a proof of concept, single center study for the donation of HCV-positive kidney to HCV negative recipient patients, with preemptive, interventional treatment with 12 weeks of commercially available DAA therapy to prevent HCV transmission upon transplantation.

Study Overview

• Status: Withdrawn
• Conditions: Kidney Diseases; Hepatitis C; Kidney Failure
• Intervention / Treatment: Drug: glecaprevir/pibrentasvir tablets

Detailed Description

The goal of this study is to determine if preoperative dosing and sustained administration of pan-genotypic DAA therapy after kidney transplantation prevents the transmission of hepatitis C virus (HCV) infection from an HCV positive donor kidney to an HCV naïve recipient.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Met MGH transplant center criteria and already listed for kidney transplant
• No available living kidney donor
• Has ≤ 730 days (two years) of accrued transplant waiting time if blood type A and ≤ 1095 days of accrued transplant waiting time if blood type B or O.
• On chronic hemodialysis or peritoneal dialysis or has a glomerular filtration rate <15mL/min/1.73m2 at the time of screening
• Must agree to birth control. Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy and at least one barrier method
• Weigh at least 50kg
• Serum ALT within normal limits with no history of liver disease
• Able to sign informed consent

Exclusion Criteria:

• AB blood type
• BMI > 35
• Any liver disease in recipient
• Pregnant or nursing (lactating) women
• Known allergy or intolerance to tacrolimus that would require administration of cyclosporine rather than tacrolimus given the known drug-drug interaction between cyclosporine and Mavyret
• Cardiomyopathy (LV ejection fraction < 50%)
• Albumin < 3g/dl or platelet count < 75 x 103/mL
• Positive donor specific antibodies or positive cross match deemed to be clinically relevant and increasing risk of rejection per the transplant surgeon or nephrologist
• Positive donor specific antibodies or positive cross match deemed to be clinically relevant and increasing risk of rejection per the transplant surgeon or nephrologist
• HCV RNA positive
• Hepatitis B surface antigen positive
• Any known liver disease or elevated liver transaminases
• Patients with primary focal segmental glomerulosclerosis (FSGS), FSGS recurring after previous transplant, or disease process with increased risk of causing early graft failure as assessed by the transplant nephrologist and/or the investigator team
• Any contra-indication to kidney transplantation per MGH center protocol
• Patients on the following medications who cannot stop therapy: carbamazepine, rifampin, St. John's wort, and ethinyl estradiol-containing oral contraceptives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment with Mavyret (glecaprevir/pibrentasvir) for HCV; 12 weeks of treatment with Mavyret	Drug: glecaprevir/pibrentasvir tablets; 12 weeks of treatment with Mavyret; Other Names: Mavyret

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Undetectable HCV RNA in blood	Negative HCV viral RNA at 12 weeks after the last dose of treatment as determined by blood test	12 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation)	Safety of Mavyret therapy in the kidney transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient.	12 weeks post treatment
Tolerability (based on number of adverse events and out of range lab values) of DAA therapy in patients undergoing kidney transplantation	Tolerability of Mavyret therapy in the kidney transplant patient will be monitored by quantifying the number of treatment related adverse events per patient and evaluating out of range laboratory results as compared to baseline/pretreatment values per patient.	12 Weeks post treatment

Collaborators and Investigators

• Sponsor: Raymond T. Chung, MD

Study record dates

Study Major Dates

• Study Start (Anticipated): February 15, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): April 15, 2021

Study Registration Dates

• First Submitted: August 2, 2018
• First Submitted That Met QC Criteria: August 6, 2018
• First Posted (Actual): August 9, 2018

Study Record Updates

• Last Update Posted (Actual): June 3, 2019
• Last Update Submitted That Met QC Criteria: May 30, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: HCV; CKD; Hepatitis C; Transplant
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Urologic Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Kidney Diseases; Hepatitis; Hepatitis C; Renal Insufficiency
• Other Study ID Numbers: 2018P001077

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anticipate to share coded data with collaborators
• IPD Sharing Time Frame: Anticipate data would be available to share within 6 months after the final patient completes the study.
• IPD Sharing Access Criteria: Coded data would be shared with collaborators who have received IRB approval to use the data and have been approved by the PI for their collaboration.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• 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