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

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03623568
• Other study ID #: 2018P001077
• Status: Withdrawn
• Phase: Phase 4
• Start date: February 15, 2019
• Est. completion date: April 15, 2021

Study information

• Verified date: May 2019
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 15, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Kidney Diseases
• Kidney Failure
• Renal Insufficiency

Intervention

Drug:
• glecaprevir/pibrentasvir tablets
12 weeks of treatment with Mavyret

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Raymond T. Chung, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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