Efficacy and Safety of Narlaprevir Used in Combination With Ritonavir in Treatment-Naïve and Failed Prior Treatment With Pegylated Interferon/Ribavirin Patients With Chronic Hepatitis C Genotype 1 (PIONEER - Study) (PIONEER)

This is an interventional treatment trial for Hepatitis C Read More

Inclusion Criteria:

• Body weight ≥ 40 and ≤ 125 kg;

• Documented infection with HCV genotype 1 (Mixed infections with other genotypes are not eligible):

  1. treatment naïve (to interferon and ribavirin); or
  2. treatment failure patients (patients must have received interferon/ribavirin at standard doses for a minimum of 12 weeks);
• Minimum HCV-RNA level of ≥10,000 IU at baseline;

• No evidence of cirrhosis; availability at Baseline of at least one of the following tests negative results:

  1. Liver biopsy showing no cirrhosis (not later than within 3 years prior to Baseline) or
  2. FibroScan elasticity score < 12.5 kPa 12 months prior to baseline or
  3. FibroTest < 0.75 12 months prior to baseline and aspartate aminotransferase (AST)/platelet ratio (APRI) of ≤ 1 during screening
• Using acceptable contraception methods for both partners from enrollment into the study until 6 months following the end of treatment;
• Willingness to give written informed consent.

Exclusion Criteria:

• Previous treatment with any HCV NS3-specific protease inhibitor and/ or other direct antiviral agents (e.g. HCV polymerase inhibitors);
• Treatment for HCV infection 30 days before the enrolment;
• Use of prohibited medications within 2 weeks prior to start of study medications (inducers or substrates of CYP3A4);
• Findings suspicious for hepatocellular carcinoma (HCC);
• Hepatic failure at present or in history;
• Auto-immune hepatitis in history;
• Anti-nuclear antibodies (ANA) titers > 1:320;
• Evidence of gallstones, choledocholithiasis and calcified gallbladder;
• HBsAg positive;
• HIV positive;
• Serum hemoglobin of <13g/dL for males and <12g/dL for females;
• Neutrophils <1500/mm3 (<1,5х109/L) at Screening;
• Platelets <150000/mm3 (<150х109/L) at Screening (patients with a platelet count >100,000/mm3 (>100х109/L) but less than 150,000/mm3 (150х109/L) can be included in the study in case a Fibroscan or FibroTest or liver biopsy during the study screening period shows no cirrhosis)
• Total bilirubin >1.6 mg/dL (>27.36 µmol/L) unless history of Gilbert's disease. If Gilbert's disease is the proposed etiology, this must be documented in the subject's chart;
• Direct bilirubin >1.5 x upper limit of normal (ULN) of the laboratory reference range at Screening;
• Serum albumin < lower limit of normal (LLN) of laboratory reference range at Screening;
• Serum creatinine >ULN of the laboratory reference at Screening;
• Serum aspartate aminotransferase (AST) / alanine aminotransferase (ALT) >5 x ULN of the laboratory reference range at Screening;
• Thyroid stimulating hormone (TSH) >1.2 ULN or <0.8 LLN;
• Contraindications to pegylated interferon, ribavirin and/or ritonavir treatment;
• Hypersensitivity to any of the study drugs;
• Active or suspected cancer;
• Psychiatric disease (moderate or severe depression, schizophrenia, bipolar disorder et al);
• Previous suicide attempt or suicidal ideation;
• Drug addiction;
• Opiate agonist substitution therapy;
• History of active gout within the past year;
• Organ transplant (except of cornea and hair transplant);
• Pregnant or nursing women;
• Men whose female partners are pregnant or planning pregnancy;
• Any medical condition that could interfere with the patient's participation and completion of the study;
• Use of other investigational drugs/ participation in other clinical trial within 30 days before the enrolment.