HCV Treatment Immune Response With Grazoprevir/Elbasvir Before or After Renal Transplant
Condition: Hepatitis C; Renal Insufficiency, Chronic; Disorder of Transplanted Kidney
MeSH terms: Hepatitis C; Hepatitis; Renal Insufficiency; Renal Insufficiency, Chronic
Intervention: Post-transplant Grazoprevir and Elbasvir
Intervention description: Treatment will be started in the post-transplant patients on day 0 with the combination pill zepatier, containing grazoprevir 100mg/elbasvir 50mg by mouth once daily. The medications will be continued for a total of 12 weeks (16 weeks if resistance mutations, RAVs, are detected)
Intervention MeSH terms: Grazoprevir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether patients treated for chronic hepatitis C
      (HCV) with zepatier (grazoprevir/elbasvir) prior to kidney transplant will have a stronger
      immune response compared to patients treated after kidney transplant. 25 patients with
      chronic kidney disease (CKD) and HCV will be treated with zepatier and 25 kidney transplant
      recipients with chronic kidney disease will be treated with zepatier. Blood markers of immune
      function will be monitored in both groups to determine their response to therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  At least 18 years of age at the time of screening

          -  Have stable renal function for one month (30 days) prior to enrollment

          -  Have Chronic HCV infection prior to transplantation with documented HCV viremia ≥
             1,000 IU/ml at screening and either documented HCV Ab positivity or HCV viremia ≥
             1,000 IU/ml at least 6 months prior to enrollment.

          -  Documented genotype 1 HCV infection prior to enrollment and after their transplant in
             the post-transplantation cohort

          -  HCV disease staging within 12 months prior to enrollment by liver biopsy, transient
             elastography, or biochemical testing

          -  Be able to give informed consent and comply with study guidelines

          -  Women of childbearing age will be required to have a negative pregnancy test at
             enrollment and use birth control throughout the duration of treatment.

        Inclusion Criteria Specific to the Pre-transplant Arm

        Patients will either be:

          -  On the transplant waiting list followed by the University of Maryland's nephrology
             clinic or the Baltimore VA's nephrology clinic

          -  On chronic hemodialysis not yet on the transplant list and followed in the
             University's hemodialysis center or in the University's nephrology clinic

          -  Have chronic kidney disease with GFR <50

        Inclusion Criteria Specific to the Post-transplant Arm

        • Patients will have undergone renal transplantation no greater than five years prior to
        enrollment and will be followed in our University's nephrology and infectious disease
        clinic. They will all have stable renal function at the time of enrollment.

        Exclusion Criteria:

          -  Documented positive hepatitis B (HBV) surface antigen, and/or HBV DNA prior to
             enrollment

          -  Any prior exposure to HCV protease inhibitor therapy

          -  HIV co-infection if on a protease inhibitor based regimen

          -  Increase in creatinine of 15% or greater within one month (30 days) of the screening
             visit

          -  Evidence of hepatocellular carcinoma at the time of enrollment

          -  Liver disease caused by an etiology other than HCV

          -  F4 or decompensated cirrhotic patients

          -  Child Pugh class B or C

          -  AST or ALT >350 within 6 months prior to enrollment

          -  Albumin < 3g/dL at the time of enrollment

          -  Platelet count < 75 at the time of enrollment

          -  History of clinically significant allergy or adverse event with protease inhibitors

          -  Evidence of the acquisition of HCV at the time of or after transplantation

          -  Pregnant or breastfeeding women

          -  Cyclosporine; St. John's Wort; Efavirenz; Phenytoin; Carbamazepine; Bosentan; HIV
             protease inhibitors; modafinil; ketoconazole; or rifampin use within 7 days of
             enrollment

          -  Coadministration of more than 20 mg atorvastatin; 10 mg rosuvastatin; 20 mg of
             fluvastatin, lovastatin or simvastatin