EBR/GZR for HCV-1b Patients Receiving Hemodialysis
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: EBR/GZR
Intervention description: Elbasvir/grazoprevir (EBR/GZR 50mg/100mg fixed dose combination [FDC]): 1 table per os per day for 12 weeks
Intervention MeSH terms: Elbasvir-grazoprevir drug combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Hepatitis C virus; Hemodialysis; Direct acting antiviral agent

Summary:

      Hepatitis C virus (HCV) infection is common in patients receiving hemodialysis. The uptake of
      antiviral therapy for these patients is limited in the era of interferon (IFN) plus ribavirin
      (RBV), probably because the sustained virologic response (SVR) rates are low and the risk of
      treatment-related adverse events (AEs) are high. In the era of IFN-free direct acting
      antiviral agents (DAAs), several studies have indicated high rates of SVR and excellent
      safety profiles to treat patients with severe renal impairment. With regard to
      elbasvir/grazoprevir (EBR/GZR) treatment, a phase 3 study (C-SURFER) study has shown 99% of
      SVR in HCV-1 patients with chronic kidney disease (CKD) stage 4 or 5. Furthermore, most
      patients tolerated the treatment well. Although the data confirmed the excellent safety and
      efficacy in HCV-1 patients with severe renal impairment, data regarding the safety and
      efficacy for Asian HCV-1b patients receiving hemodialysis is lacking. Therefore, we aim to
      evaluated the safety and efficacy of EBR/GZR for 12 weeks in treatment-naive and
      treatment-experienced HCV-1b patients receiving hemodialysis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  20 yeas or more

          -  Male or female

          -  Body mass index (BMI) 18.5-35.0 kg/m2

          -  Chronic HCV infection, defined as patients who meet as least one of the two following
             criteria:

               1. Anti-HCV antibody (Abbott HCV EIA 2.0, Abbott Laboratories, Abbott Park,
                  Illinois, USA) or HCV RNA > 1,000 IU/mL for at least 6 months before screening

               2. Positive HCV RNA > 1,0000 IU/mL (Cobas TaqMan HCV Test v2.0, Roche Diagnostics
                  GmbH, Mannheim, Germany, low limit of quantification (LLOQ): 25 IU/mL) at the
                  time of screening with a liver biopsy consistent with chronic HCV infection

          -  HCV genotype 1 (HCV GT-1b) infection (Abbott RealTime HCV genotype II, Abbott
             Molecular Inc. Illinois, USA)

          -  Treatment-naïve or treatment-experienced (including patients who relapsed, who had
             virological breakthrough, or who were null-responsive to IFN-based therapies)

          -  HCV RNA > 10,000 IU/mL at screening

          -  Estimated glomerular filtration (eGFR) rate < 15 mL/min/1.73m2 as assessed by modified
             of diet in renal disease (MDRD) equation, and receiving regular hemodialysis

        Exclusion Criteria:

          -  HCV infection other than HCV GT-1b

          -  HBV or HIV coinfection

          -  Presence of decompensated cirrhosis (Child-Pugh class B or C)

          -  Any primary cause of liver disease other than chronic HCV infection, including but not
             limited to the following

               1. Hemochromatosis

               2. Alfa-1 antitrypsin deficiency

               3. Wilson's disease

               4. Autoimmune hepatitis

               5. Alcoholic liver disease

               6. Drug-induced hepatitis

               7. Screening laboratory analyses showing any of the following results

                    -  Hemoglobin (Hb) level < 10 g/dL

                    -  Absolute neutrophil count (ANC) < 1,500 cells/μL

                    -  Platelet count < 70,000 cells/mm3

                    -  International normalized ratio (INR) > 2.0

                    -  Albumin (Alb)< 3.0 g/dL

                    -  Bilirubin (Bil) > 2.0 mg/dL

                    -  Alanine aminotransferase (ALT) > 10X upper limit of normal (ULN)

                    -  Aspartate aminotransferase (AST) > 10X upper limit of normal (ULN)

                    -  Serum alfa-fetoprotein (AFP) > 100 ng/mL

          -  Presence of hepatocellular carcinoma (HCC) on imaging studies such as computed
             tomography (CT) scan or magnetic resonance imaging (MRI)

          -  History of malignancy (except cutaneous melanoma) within 5 years at the screening

          -  Organ transplantation other than cornea and hair (prior renal transplantation with
             graft failure not included)

          -  Prior exposure to investigational agents for HCV (direct acting antiviral agents,
             host-targeting agents, or therapeutic vaccines)

          -  Pregnancy

          -  Unwilling to have contraception during the study period

          -  Unwilling to provide informed consent