EBR/GZR for HCV-1b Patients Receiving Hemodialysis

• Status: Completed
• Trial end date: 2020-02-03
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Taiwan University Hospital
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Elbasvir-grazoprevir drug combination

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