Short Term Treatment With BI 201335, Peginterferon-alpha 2a and Ribavirin in Hepatitis c Virus Genotype-1 Treatment-naïve Patients (SILEN-C3)

Study Overview
=================
Brief Summary
-----------------
To compare the antiviral efficacy and safety of a 12-week with a 24-week treatment of BI 201335 at a dose of 120 mg once daily, with a 24-week background of pegylated interferon-alpha 2a (PegIFN) plus ribavirin (RBV), in treatment-naïve patients infected with hepatitis C virus (HCV) genotype 1

Official Title
-----------------
Antiviral Effect and Safety of Once Daily BI 201335 NA in Hepatitis C Virus Genotype 1 Infected Treatment-naive Patients for 12 or 24 Weeks as Combination Therapy With Pegylated Interferon-alpha 2a and Ribavirin (Randomised, Open Label, Phase II)

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: BI 201335
* Drug: BI 201335
* Drug: Pegylated Interferon-alpha (IFN)
* Drug: Ribavirin (RBV)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Chronic hepatitis C infection of genotype 1 Therapy-naïve to interferon, pegylated interferon, and ribavirin HCV viral load > 100.000 IU/ml at screening Liver biopsy or fibroscan within two years prior to screening that provides evidence of any degree of fibrosis or cirrhosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 Age 18 to 70 years Exclusion criteria: HCV of mixed genotype (1/2, 1/3, and 1/4) . Patients who have been previously treated with at least one dose of any protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection Positive for HIV-1 or HIV-2 antibodies Hepatitis B virus (HBV) infection Decompensated liver disease, or history of decompensated liver disease Active malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse (except cannabis) within the past 12 months. Body Mass Index < 18 or > 35 kg/m2. Usage of any investigational drugs within 30 days prior to enrolment Alpha fetoprotein value >100ng/mL at screening; Total bilirubin > 1.5 x ULN with ratio of direct/indirect > 1. ALT or AST level > 10 x ULN

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: short arm<br>patients to receive BI201335 with PegIFN/RBV for 12 wks followed by 12 weeks PegIFN/RBV with a 3 days lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 NA 3 days after first administration of PegIFN/RBV) | Drug: BI 201335<br>* BI 201335<br>Drug: Pegylated Interferon-alpha (IFN)<br>* Pegylated Interferon-alpha<br>Drug: Ribavirin (RBV)<br>* Ribavirin (RBV)<br>|
| Experimental: long arm<br>patients to receive BI201335 with PegIFN/RBV for 24 wks with a 3 days lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 NA 3 days after first administration of PegIFN/RBV) | Drug: BI 201335<br>* BI 201335<br>Drug: Pegylated Interferon-alpha (IFN)<br>* Pegylated Interferon-alpha<br>Drug: Ribavirin (RBV)<br>* Ribavirin (RBV)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological Response at Week 28 (W28VR) | Virological response at Week 28: The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at Week 28. | 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rapid Virological Response at Week 4 (RVR) | Rapid virological response at week 4 (RVR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 4. | 4 weeks | 
| Virological Response at Week 24 (W24VR) | virological response at week 24 (W24VR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 24. | 24 weeks | 
| Virological Response at Week 36 (W36VR) | Virological response at week 36 (W36VR): the patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 36. | 36 weeks | 
| End of Treatment Response (ETR) | End of Treatment Response (ETR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at end of all therapy. | up to 48 weeks | 
| Sustained Virological Response (SVR24) at 24 Weeks After Completion of All Therapy | Sustained Virological Response (SVR24) at 24 weeks: The patients who reached plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at 24 weeks after completion of all Hepatitis C virus (HCV) therapy. | 72 weeks | 
| Viral Load (HCV RNA) at All Visits During Treatment and Follow-up | Viral load of Hepatitis C virus Ribonucleic acid (HCV RNA) at all visits during treatment (TRT) and follow-up, ie. change from baseline viral load at all visits. | From baseline to 72 weeks | 
| Time to Reach a Plasma HCV RNA Level BLD While on Treatment | Time to reach a plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) level below the lower limit of detection (BLD) while on treatment | 48 weeks | 
| Laboratory Test Abnormalities and Study Medication Tolerabilities | Participants with possible clinically significant laboratory test abnormalities observed in functional groups: Haematology, Coagulation, Electrolytes, Enzymes, Substrates and Differentials, automatic. | 48 weeks | 
| Number of Participants With Clinically Relevant Abnormalities Vital Signs, and Physical Examination | No number of participants with clinically relevant abnormalities in vital signs and physical examination. | 48 weeks | 
| Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (1) | Change from baseline (CFB) in Red blood cells. | baseline and 48 weeks | 
| Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (2) | Change from baseline (CFB) in haematocrit and Eosinophils. | baseline and 48 weeks | 
| Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (3) | Change from baseline (CFB) in Platelets and white blood cells. | baseline and 48 weeks | 
| Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (4) | Change from baseline (CFB) in Sodium, Bicarbonate, Cholesterol total, Triglyceride, and Glucose. | baseline and 48 weeks | 
| Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (5) | Change from baseline (CFB) in AST/GOT, ALT/GPT, Alka. phosphatase, GGT, Creatine kinase, Lipase, and Amylase. | baseline and 48 weeks | 
| Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (6) | Change from baseline (CFB) in PT-INR (ratio). | baseline and 48 weeks |