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)

• Status: Completed
• Trial end date: 2017-02-21
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study was to confirm that combination of narlaprevir (NVR) and ritonavir (RTV) used as a metabolic inhibitor with pegylated interferon (PEG-INF) and ribavirin (RBV) leads to a superior Sustained Virological Response (SVR) rate compared to treatment with pegylated interferon and ribavirin in treatment-naïve and treatment failure patient populations.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: R-Pharm
• Treatments: Interferon alpha-2; Interferon-alpha; Interferons; Peginterferon alfa-2a; Peginterferon alfa-2b; Ribavirin; Ritonavir

Criteria

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.