PrOD for Non-Cirrhotic Patients With HCV-1b Receiving Hemodialysis
Condition: Hepatitis Viruses
MeSH terms: Hepatitis A; Hepatitis
Intervention: PTV/r/OBV/DSV
Intervention description: Viekirax/Exviera for 12 weeks
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 20 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Hepatitis C virus; Hemodialysis; Direct acting antiviral agents

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
      ombitasvir/paritaprevir/ritonavir plus dasabuvir (PrOD) treatment, a phase 2 study (RUBY-1)
      study has shown 90% of SVR in treatment-naive HCV-1 patients with chronic kidney disease
      (CKD) stage 4 or 5. Among the HCV-1b patients, who received PrOD for 12 weeks, all 7 patients
      achieved SVR. Although the data confirmed the excellent safety and efficacy in HCV-1b
      patients with severe renal impairment, the patient number was small and the data with regard
      to treatment-experienced patients was lacking. Therefore, we aimed to evaluated the safety
      and efficacy of ProD for 12 weeks in treatment-naive and treatment-experienced HCV-1b
      patients receiving hemodialysis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ages of 20 to 70 yeas

          -  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 enzyme-linked immunosorbent assay [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
                  Gesellschaft mit beschränkter Haftung [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 GT-1b infection (Abbott RealTime HCV genotyping 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

          -  Absence of cirrhosis with documented results of one of the following criteria:

               1. Liver biopsy within 24 months prior to or during screening demonstration the
                  absence of cirrhosis, e.g. METAVIR score ≤ 3 or Ishak score ≤ 4.

               2. A screening transient elastography (Fibroscan) result of < 12.5 kilopascal (kPa)

               3. A screening Fibrosis Index Based on 4 markers (FIB-4) of ≤ 1.45 and Aspartate
                  Aminotransferase to Platelet Ratio Index (APRI) of ≤ 2

               4. Subjects with non-qualifying FIB-4/APRI or Fibroscan result may only be enrolled
                  if they have a qualifying liver biopsy within 24 months prior to or during
                  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

          -  Hepatitis B virus (HBV) or HIV co-infection

          -  Presence of cirrhosis (Child-Puge class A, 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

          -  Screening laboratory analyses showing any of the following results

               1. Hemoglobin (Hb) level < 10 g/dL

               2. Absolute neutrophil count (ANC) < 1,500 cells/μL

               3. Platelet count < 60,000 cells/mm3

               4. International normalized ratio (INR) > 2.0

               5. Albumin (Alb) < 2.8 g/dL

               6. Bilirubin (Bil) > 3.0 mg/dL

               7. Alanine aminotransferase (ALT) > 5X upper limit of normal (ULN)

               8. Aspartate aminotransferase (AST) > 5X upper limit of normal (ULN)

               9. 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 [12] Unwilling to provide
             informed consent