Japanese Pegylated Interferon (PegIFN) Alfa-2b/Ribavirin (RBV) Combination Trial

Study Overview
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Brief Summary
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The aim of this trial is to evaluate the safety and efficacy of BI 201335 given for 12 or 24 weeks in combination with PegIFN alfa-2b/RBV given for 24 or 48 weeks in chronic genotype 1 hepatitis C virus infected treatment-naïve and treatment-experienced Japanese patients

Official Title
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Safety, Efficacy and Pharmacokinetics of BI 201335 NA in Patient With Genotype 1 Chronic Hepatitis C Virus Infection in Combination With Pegylated Interferon Alfa-2b and Ribavirin - Cohort 1 for Treatment-naive Patients: Randomised, Double-blind Part of BI 201335 NA for 12 or 24 Weeks - Cohort 2 for Treatment-experienced Patients: Open-label Part of BI 201335 NA for 24 Weeks

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: BI 201335 high dose
* Drug: BI 201335 low dose
* Drug: BI 201335 high dose
* Drug: BI 201335 high dose


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detected HCV RNA at screening in addition to: positive anti-HCV antibodies or detected HCV RNA at least 6 months before screening; or, liver biopsy consistent with chronic HCV infection. HCV genotype 1 infection confirmed by genotypic testing at screening (For Cohort 1 only) Therapy-naïve to interferon, pegylated interferon, and ribavirin (For Cohort 2 only) Confirmed prior virological failure (null response, partial response, breakthrough or relapse) with an approved dose of PegIFN alfa/RBV or IFN beta/RBV for at least 12 weeks and with an 8-week washout period before screening HCV RNA = 100,000 IU/mL at screening Documentation of a liver biopsy within 3 years or fibroscan within 6 months before randomization (Visit 2) Age 20 to 70 years Female patients who are infertile or who are of childbearing potential with a negative pregnancy test and agreeing to use one accepted method of birth control in addition to the use of a condom by their male partners. or Male patients who are infertile, who are without pregnant female partners or who consistently and correctly use condoms. Signed informed consent form before trial participation Exclusion criteria: HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening, Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. Steatosis diagnosed incidentally (e.g. by biopsy) without clinical relevance is not an exclusion criterion. HIV co-infection, Hepatitis B virus (HBV) infection based on presence of hepatitis B surface antigen (HBsAg), Active malignancy, or history of malignancy within the last 5 years prior to screening (with an exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix), Active or, history of alcohol or illicit drug abuse within the past 12 months, A condition that is defined as one which in the opinion of investigator may put the patient at risk because of participation in this study, may influence the results of this study, or limit the patient's ability to participate in this study, Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study, Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to screening. Patients being treated with oral antivirals such as acyclovir, famciclovir or valacyclovir for recurrent herpes simplex infection; or with oseltamivir or zanamivir for influenza A infection, may be screened, Received silymarin (milk thistle), glycyrrhizin (Stronger Neo-Minophagen C; SNMC), or Sho-saiko-to (SST) within 28 days prior to randomization (Visit 2) and throughout the treatment phase of this trial, (For Cohort 2 only) Patients who have been previously treated with at least one dose of any antiviral or immunomodulatory drug other than (pegylated) interferon alfa, interferon beta or ribavirin for acute or chronic HCV infection including and not restricted to protease or polymerase inhibitors, Known hypersensitivity to any ingredient of the study drugs, Alpha fetoprotein value >100 ng/mL at screening; if >20 ng/mL and =100 ng/mL, patients may be included if there is no evidence of liver cancer in an appropriate imaging study (e.g., ultrasound, CT scan, or MRI) within last 6 months prior to randomization (Visit 2), Other exclusion criteria related to pegylated interferon and/or ribavirin restrictions are not listed here.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. BI 201335 low dose plus PegIFN/RBV<br>low dose BI 201335 NA once daily for 12 or 24 weeks combined with PegIFN/RBV for 24 or 48 weeks in treatment-naive patients | Drug: BI 201335 low dose<br>* BI 201335 low dose with PegIFN/RBV<br>|
| Experimental: 2. BI 201335 high dose plus PegIFN/RBV<br>high dose BI 201335 NA once daily for 12 weeks combined with PegIFN/RBV for 24 or 48 weeks in treatment-naive patients | Drug: BI 201335 high dose<br>* BI 201335 high dose with PegIFN/RBV<br>|
| Experimental: 3. BI 201335 high dose plus PegIFN/RBV<br>high dose BI 201335 NA once daily for 24 weeks combined with PegIFN/RBV for 24 or 48 weeks in treatment-experienced (relapser) patients | Drug: BI 201335 high dose<br>* BI 201335 high dose with PegIFN/RBV<br>|
| Experimental: 4. BI 201335 high dose plus PegIFN/RBV<br>high dose BI 201335 NA once daily for 24 weeks combined with PegIFN/RBV for 48 weeks in treatment-experienced (null responder, partial responder, breakthrough) patients | Drug: BI 201335 high dose<br>* BI 201335 high dose with PegIFN/RBV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Investigator Defined Drug-related Adverse Events | Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator. | Up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (SVR12), Defined as Plasma HCV RNA Undetectable at 12 Weeks After End of Treatment (EOT) | Plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level <25 IU/mL (undetected) 12 weeks after the originally planned treatment duration | EOT (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60) | 
| Sustained Virological Response (SVR24), Defined as Plasma HCV RNA Undetectable at 24 Weeks After End of Treatment (EOT) | Plasma HCV RNA level <25 IU/mL (undetected) 24 weeks after the originally planned treatment duration | EOT (up to Week 24 or 48) and 24 weeks after the EOT (up to Week 48 or 72) | 
| Early Treatment Success (ETS), Defined as Plasma HCV RNA <25 IU/mL at Week 4 and HCV RNA Undetectable at Week 8 | Plasma HCV RNA level <25 IU/mL (detected or undetected) at Week 4 and HCV RNA <25 IU/mL (undetected) at Week 8 | up to 8 weeks | 
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EOT) When SVR12=YES | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | EOT (up to Week 24 or 48) | 
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EOT) When SVR12= NO | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | EOT (up to Week 24 or 48) | 
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | 12 weeks after the EOT (up to Week 36 or 60) | 
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | 12 weeks after the EOT (up to Week 36 or 60) | 
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EOT) When SVR12=YES | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | EOT (up to Week 24 or 48) | 
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EOT) When SVR12=NO | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | EOT (up to Week 24 or 48) | 
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | 12 weeks after the EOT (up to Week 36 or 60) | 
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline | 12 weeks after the EOT (up to Week 36 or 60) |