Antiviral Efficacy, Pharmacokinetics and Safety of BILN 2061 ZW in Patients With Cirrhosis and Chronic Hepatitis C

Inclusion criteria

• Female or male sex, age of 18 years or older
• Chronic Hepatitis C virus (HCV) infection
• Liver biopsy consistent with active HCV infection obtained within the last 36 months.
• No previous clinical evidence of decompensated cirrhosis. Present cirrhosis status consistent with grade A, according to Child-Turcotte-Pugh classification, confirmed at screening
• No evidence of significant gastroesophageal varices (> grade 1 or other risk factors) according to fiberoptic endoscopy performed within the last 12 months
• No evidence of Hepatocellular carcinoma (HCC) by ultrasound performed at screening
• Written informed consent consistent with International Committee on Harmonization (ICH) / Good Clinical Practice (GCP) and local legislation given prior to any study procedures
• HCV of genotype I
• HCV load greater than 50,000 copies messenger ribonucleic acid (mRNA) per ml serum at screening

Exclusion criteria

• Women of childbearing potential or breastfeeding women. Postmenopausal women less than 6 months after last menses, surgically sterilized or hysterectomised less than 3 months after operation or not having negative serum pregnancy test
• Males not using an adequate form of contraception (condom, sterilization at least 6 months post operation) in case their partner is of childbearing potential (criteria see above) and is not using an adequate form of contraception (hormonal contraceptives, oral or injectable/ implantable, intra-uterine device (IUD))
• Any other or additional plausible cause for chronic liver disease, including the presence of other viruses known or suspected to cause hepatitis
• Evidence of gastroesophageal varices
• Any histological evidence of hepatocytic dysplasia
• Following serological constellations: Hepatitis B surface (HBs)-Ag positive OR anti-Hepatitis B core (HBc) positive with anti- HBs negative OR anti-HAV IgM positive OR anti-Human immunodeficiency Virus (HIV) positive
• History of abuse of alcohol within the past twelve months
• Planned or concurrent usage of any other pharmacological therapy at screening, including any antiviral therapy
• Any concurrent infectious disease requiring antimicrobial treatment
• History of malignancy (except for previously cured squamous cell or basal cell carcinoma of the skin)
• Usage of any investigational drug within thirty (30) days prior to enrolment; or the planned usage of an investigational drug during the course of the current study
• Known hypersensitivity to drugs
• Inability to comply with the protocol
• Prior or present Child´s B or C liver diseases -

• Bilirubin - refer to following exclusion criterion
• Prothrombin time < 70%
• Albumin < 3.5 g/dl
• Clinical evidence of ascites
• Clinical evidence of encephalopathy
• Clinically apparent jaundice or a total bilirubin or alkaline phosphatase exceeding 2.0 x upper limit of normal (ULN) at screening
• ALT or AST >= 10 x ULN at screening
• A platelet count of less than 80.000 platelets per mm3 at screening
• White blood cell count of less than 2,000 cells per mm3 at screening
• AFP > 100 ng/ml
• Splenectomy
• Positive test for illicit or unprescribed drugs or medications at screening. Positive test for cannabis may be allowed if the investigator assesses this result not as clinically significant
• Patients with any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening