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

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ClinicalTrials.gov Identifier: NCT02743897
Recruitment Status : Recruiting
First Posted : April 19, 2016
Last Update Posted : September 28, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
End Stage Renal Disease Drug: Zepatier Phase 1 Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Kidney Transplants From Hepatitis C-Positive Donors
Study Start Date : May 2016
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : August 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Zepatier



Primary Outcome Measures :
  1. 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)

  2. Major adverse events attributable to HCV therapy in post-kidney transplant patients post-kidney transplant patients. [ Time Frame: baseline to 52 weeks ]


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Ages Eligible for Study:   40 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Recipient

Inclusion Criteria:

  • Must be waitlisted for a kidney transplant
  • Listed for an isolated kidney transplant with <=913 days of accrued transplant waiting time and/or <=913 days of dialysis time
  • No available living kidney donor
  • Blood group A, B, or O
  • Between 40-65 years of age
  • Have a panel reactive antibody level ≤97%
  • Obtained agreement for participation from the patient's treating transplant nephrologist
  • No evident contraindication to liver transplantation (Only subjects who would be eligible for a liver transplant if HCV caused them to experience liver failure will be enrolled in this study. To be deemed eligible for a liver transplant at Penn, all patients (not only study subjects) must have adequate cardiac function and must be examined by both a hepatologist and a liver transplant surgeon. These two requirements represent the major differences between evaluation processes for kidney and liver transplants.
  • Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 months after transplantation
  • 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
  • No active illicit substance abuse
  • Weigh at least 50kg
  • Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA level
  • 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 assessed by the transplant nephrologist and/or the investigator team
  • 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
  • Blood group AB(due to short expected waiting time on the kidney transplant waiting list)
  • 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.)
  • Cardiomyopathy (e.g., left-ventricular heart failure, pulmonary hypertension) that would preclude liver transplantation, as per the discretion of the transplant hepatologist (dg) and abdominal transplant surgeon who will evaluate the patient.

Donor Organ Criteria

Inclusion criteria:

  • Detectable HCV RNA
  • Genotype 1 or 4 HCV
  • Age ≤60 years
  • Kidney donor profile index (KDPI) score ≤0.856

Exclusion criteria:

  • Diabetes mellitus I or II
  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02743897


Contacts
Contact: David Goldberg, MD, MSCE (307) 22-THINK thinker@med.upenn.edu
Contact: Peter Reese, MD, MSCE (307) 22-THINK thinker@med.upenn.edu

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: David Goldberg, MD, MSCE University of Hospital of Pennsylvania
Principal Investigator: Peter Reese, MD, MSCE University of Hospital of Pennsylvania

Additional Information:
Publications:
Reddy KR FS, et al. Ledipasvir/Sofosbuvir with Ribavirin for the Treatment of HCV in Patients with Post Transplant Recurrence: Preliminary Results of a Prospective, Multicenter Study. Hepatology. 2014;60:200A
Van Deerlin, V. (December 2015). Hepatitis C Virus Genotyping (GenMark Assay) Validation Summary
Pawlak R RJ, Maranan G, Michel-Treil V, Schutzbank T. A Comparative Evaluation of the Siemens VERSANT HCV Genotype 2.0 (LiPA) and GenMark eSensor HCV Direct Genotyping Tests. CVS 2013 Covance; 2013
Dahl A HD, Ogorek T, Hansen G. Comparison of the GenMark Direct Genotype Assay with the LiPA Genotype Assay Using a Diverse Spectrum of HCV Clinical Samples Encountered in a High Risk Inner City HCV Population. CVS 2013 Hennepin; 2013.
Woodberry M SK, Castor J, Cook L, Jerome K. Genotyping of Hepatitis C Virus by the Genmark DX Esensor HCVG Direct Test. CVS 2013 UW-Seattle 2013
U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute. (June 2010). Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
Merck Sharp & Dohme Corporation (January 2016). ZEPATIER™ tablets. Highlights of Prescribing Information. 2016.
Merck Sharp & Dohme Corporation (July 2015). Elbasvir (MK-8742). Investigator's Brochure (8th Ed.). 2015.
Merck Sharp & Dohme Corporation (July 2015). Grazoprevir (MK-5172). Investigator's Brochure (10th Ed.). 2015.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02743897     History of Changes
Other Study ID Numbers: 823833
First Posted: April 19, 2016    Key Record Dates
Last Update Posted: September 28, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University of Pennsylvania:
end-stage renal disease

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Renal Insufficiency
Hepatitis
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Urologic Diseases
Elbasvir-grazoprevir drug combination
Antiviral Agents
Anti-Infective Agents