Safety, Antiviral Effect and PK of BI 207127 + BI 201335 +/- RBV for 4 up to 40 Weeks in Patients With Chronic HCV Genotype 1 Infection

Safety, Antiviral Effect and Pharmacokinetics of BI 207127 in Combination With BI 201335 and With or Without Ribavirin for 4, 16, 24, 28 or 40 Weeks in Patients With Chronic HCV Genotype 1 Infection (Randomized Phase Ib/II)

The substances BI 201335 and BI 207127 are being developed for the treatment of chronic hepatitis C virus infection. BI 201335 and BI 207127 work by preventing the virus from replicating.

The currently available medications pegylated interferon alfa and ribavirin for hepatitis C ca have considerable adverse events in patients and in many cases are not sufficiently effective. This is particularly the case in treatment of patients infected with genotype 1 of HCV.

A combination therapy of these new substances without pegylated interferon alfa may be associated with fewer adverse events that currently available (pegylated interferon-alfa-based) medication and may also provide a treatment option to the large number of patients with contraindications or intolerance to pegylated interferon alfa.

This clinical trial (1241.21) currently consists of 3 distinct studies: Part 1, Part 2 and Part 3.

Part 1 (SOUND-C1) is a 2 armed study as described in experimental arms 1 and 2 below (actual enrollment: 56 patients; randomized and treated: 32) Part 2 (SOUND-C2) is a 5 armed study as described in experimental arms 3 to 7 below (actual enrollment: 465; randomized and treated: 362) Part 3 (SOUND-C3) includes 3 arms as described in experimental arms 8 to 10 below (83 patients randomized and treated)

Inclusion criteria:

• Chronic hepatitis C virus (HCV) infection of genotype (GT) 1
• Parts 1-3:Treatment naive to Interferon -alfa (IFN), Pegylated interferon -alfa (PegIFN), ribavirin (RBV), and any direct acting antiviral agent for chronic hepatitis C
• Part 4: Treatment experienced with confirmed prior virological failure to an approved dose of PegIFN/RBV (null-response)
• HCV RNA >=10,000 IU/mL at screening
• Liver biopsy within two years or fibroscan within six months prior to baseline
• Liver biopsy within two years or fibroscan within 6 months prior to screening
• Age 18-75 years

Exclusion criteria:

• Hepatitis C virus (HCV) infection of mixed genotype
• Evidence of liver disease due to causes other than chronic HCV infection
• Positive ELISA for human immunodeficiency virus (HIV)
• Hepatitis B virus (HBV) infection
• Decompensated liver disease or history of decompensated liver disease
• Active or suspected malignancy within the last 5 years
• Ongoing or historical photosensitivity or recurrent rash
• History of alcohol or drug abuse (except cannabis) within the past 12 months
• Body mass index (BMI)I <18 or > 35 kg/m2
• Usage of any investigational drugs within 30 days prior to enrolment, or 5 half-lives, whichever is longer; o the planned usage of an investigational drug during the course of the current study
• Known hypersensitivity to any ingredient of the study drugs
• A condition that is defined as one which in the opinion of the investigator may interfere with the patient's capability for participation in the trial or may influence the results of the trial
• Alpha fetoprotein >100ng/mL at screening; if >20ng/mL and <=100ng/mL, patients can be included if there is no evidence of liver cancer in an appropriate imaging study within 6 months prior to randomisation
• Total bilirubin > 2 mg/dL with ratio of direct/indirect > 1
• AST or ALT >5xULN
• INR prolonged to >1.7xULN
• Requirement for chronic systemic corticosteroids
• Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to enrolment or 5 half-lives, whichever is longer
• Received silymarin or glycyrrhizin or Sho-saiko-to within 30 days prior to enrolment
• Contraindications pertaining to PegIFN or RBV