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Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors (HCV) (THINKER)

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ClinicalTrials.gov Identifier: NCT02743897
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : February 18, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE April 15, 2016
First Posted Date  ICMJE April 19, 2016
Last Update Posted Date February 18, 2019
Actual Study Start Date  ICMJE May 2016
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2017)
  • Post-treatment sustained virologic response (SVR) [ Time Frame: baseline to 24 weeks ]
    The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR-12; negative HCV RNA 12 weeks after completing Zepatier therapy) / (number of subjects treated with Zepatier post-kidney transplantation)
  • Major adverse events attributable to HCV therapy in post-kidney transplant patients post-kidney transplant patients. [ Time Frame: baseline to 52 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 15, 2016)
  • Post-treatment sustained virologic response (SVR) [ Time Frame: baseline to 16 weeks ]
    The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR-12; negative HCV RNA 12 weeks after completing Zepatier therapy) / (number of subjects treated with Zepatier post-kidney transplantation)
  • Determine if there are major adverse events attributable to HCV therapy in post-kidney transplant patients. [ Time Frame: baseline to 16 weeks ]
Change History Complete list of historical versions of study NCT02743897 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors (HCV)
Official Title  ICMJE Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors
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 Zepatier after the single kidney transplantation.
Detailed Description Open-labelled pilot clinical trial of Zepatier (MK-5172 and MK-8742/Grazoprevir + Elbasvir) in 40 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 with genotype 1 or 4 HCV, and then will receive 12 weeks of Zepatier after kidney transplantation when infection with HCV is confirmed in these kidney transplant recipients. Treatment will be complete after 12 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE End Stage Renal Disease
Intervention  ICMJE Drug: Zepatier
Study Arms  ICMJE Experimental: Zepatier (grazoprevir 100mg and elbasvir 50 mg) once daily
Zepatier 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: Drug: Zepatier
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2019)
75
Original Estimated Enrollment  ICMJE
 (submitted: April 15, 2016)
10
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Subject:

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 30-65 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
  • Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA
  • Able to provide informed consent

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:

Inclusion Criteria

  • Detectable HCV RNA
  • Genotype 1 or 4 HCV
  • 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

  • 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David Goldberg, MD, MSCE (307) 22-THINK thinker@med.upenn.edu
Contact: Peter Reese, MD, MSCE (307) 22-THINK thinker@med.upenn.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02743897
Other Study ID Numbers  ICMJE 823833
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: David Goldberg, MD, MSCE University of Hospital of Pennsylvania
Principal Investigator: Peter Reese, MD, MSCE University of Hospital of Pennsylvania
PRS Account University of Pennsylvania
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP