Transplanting Hepatitis C Kidneys Into Negative Kidney Recipients

NCT ID: NCT02743897

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-01
• Study Completion Date: 2022-12-31

Brief Summary

This study is being conducted to determine safety and effectiveness of transplanting kidneys from Hepatitis C-positive donors into Hepatitis C-negative patients on the kidney transplant waitlist, who will then be treated with the appropriate direct-acting antiviral (DAA) after the single kidney transplantation.

Detailed Description

Open-labelled pilot clinical trial of Zepatier (Grazoprevir + Elbasvir), Mavyret (Glecaprevir + Pibrentasvir), Epclusa (Sofosbuvir + Velpatasvir), or another appropriate DAA in at least 75 HCV-negative subjects with end-stage renal disease receiving a kidney transplant from a HCV-positive donor. Eligible subjects will receive a kidney transplant from a deceased-donor, and then will receive DAA treatment after kidney transplantation when infection with HCV is confirmed in these kidney transplant recipients. Treatment will be complete after 12 weeks for most subjects.

Conditions

End Stage Renal Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Direct-acting antiviral treatment for HCV

Group Type: EXPERIMENTAL

Zepatier

Intervention Type: DRUG

Zepatier (grazoprevir 100mg and elbasvir 50 mg once daily) is taken by mouth for 12 weeks unless a genetic variation is detected. In this case treatment with Zepatier will be extended to 16 weeks. Study subjects with treatment failure will be provided open-label Zepatier + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

Mavyret

Intervention Type: DRUG

Mavyret (glecaprevir 100 mg and pibrentasvir 40 mg) is taken by mouth for 8 weeks. Study subjects with treatment failure will be provided an alternative DAA + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

Interventions

Zepatier

Zepatier (grazoprevir 100mg and elbasvir 50 mg once daily) is taken by mouth for 12 weeks unless a genetic variation is detected. In this case treatment with Zepatier will be extended to 16 weeks. Study subjects with treatment failure will be provided open-label Zepatier + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

Intervention Type: DRUG

Mavyret

Mavyret (glecaprevir 100 mg and pibrentasvir 40 mg) is taken by mouth for 8 weeks. Study subjects with treatment failure will be provided an alternative DAA + sofosbuvir (sovaldi) 400mg + Ribavirin (generic), renally dosed based on creatinine clearance per the manufacturer guidelines.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Must be waitlisted for a kidney transplant (dialysis is not a requirement if a patient is waitlisted)
• Listed for an isolated kidney transplant with ≤2555 days of accrued transplant waiting time and/or ≤2555 days of dialysis time for blood group A, B, or O, by enrollment
• Listed for an isolated kidney transplant with ≤1825 days of accrued transplant waiting time and/or ≤1825 days of dialysis time for blood group AB, by enrollment
• No available living kidney donor
• Between 30-70 years of age, by enrollment
• Have a panel reactive antibody level ≤97%
• eGFR <15ml/min/1.73m2 as calculated using the 4 variable MDRD equation
• Obtained agreement for participation from the patient's treating transplant nephrologist
• Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 months after transplantation
• No active illicit substance abuse
• Weigh at least 50kg
• Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage
• Both men and women must agree to use at least one barrier method to prevent any secretion exchange
• Able to provide informed consent

• Detectable HCV RNA
• Age ≤60 years
• Study modified Kidney donor profile index (KDPI) score ≤0.856 - calculated as if the kidney were HCV-negative (https://optn.transplant.hrsa.gov/resources/allocation-calculators/kdpi-calculator/)

Exclusion Criteria

• Hepatocellular carcinoma
• Patients with primary focal segmental glomerulosclerosis (FSGS), FSGS recurring after previous transplant, or disease process with increased risk of causing early graft failure as per the treating nephrologist
• HIV positive
• HCV RNA positive (can be isolated HCV antibody positive provided the subject has no history of previously treated HCV)
• Hepatitis B surface antigen positive
• Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes
• Persistently elevated liver transaminases
• Significant hepatic fibrosis on screening elastography (≥f2 fibrosis)
• Pregnant or nursing (lactating) women
• Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and Zepatier
• Waitlisted for a multi-organ transplant (e.g., pancreas-kidney, heart-kidney, etc.)
• Significant cardiomyopathy defined as either:

• Left ventricular ejection fraction <40% on most recent echocardiogram
• Left ventricular ejection fraction ≥40% but <50% on most recent echocardiogram with an <5 METS of exercise tolerance
• Reversible ischemia on stress testing without revascularization

Donor Organ Selection:

• Anatomical issues in the kidney allograft that raise the risk of post-transplant complications (e.g., number or length of renal arteries or veins)
• Confirmed HIV positive
• Confirmed HBV positive (positive Hepatitis B surface antigen and/or HBV DNA)
• Known previously failed treatment for HCV using a regimen with a direct-acting antiviral (can have received interferon monotherapy and/or interferon + ribavirin combination therapy)

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stacey Prenner, MD

Role: PRINCIPAL_INVESTIGATOR

University of Hospital of Pennsylvania

Peter Reese, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

University of Hospital of Pennsylvania

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_HCV_NS5A_Genotype&tabview=true

Quest Diagnostics, Inc. (December 2014). Test summary guide. Hepatitis C Viral RNA Genotype 1 NS5a Drug Resistance.

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dc637c8f-9669-4bc5-8787-1fd5abaa588e.

Sandoz, Inc. (May 2015) Ribavirin capsule. Highlights of Prescribing Information. 2015.

Other Identifiers

823833

Identifier Type: -

Identifier Source: org_study_id