PrOD for Non-Cirrhotic Patients With HCV-1b Receiving Hemodialysis

• Status: Completed
• Trial end date: 2018-12-25
• 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 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.

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

Details

• Lead Sponsor: National Taiwan University Hospital
• Collaborator: AbbVie

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