Efficacy and Safety of BI 201335 (Faldaprevir) in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-Experienced Genotype 1 Hepatitis C Infected Patients (STARTverso 3)

Study Overview
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Brief Summary
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The aim of this trial is to evaluate the efficacy and the safety of BI 201335 given for 12 or 24 weeks in combination with PegIFN/RBV given for 48 weeks as compared to PegIFN/RBV alone in chronic GT-1 hepatitis C virus infected patients who failed a prior PegIFN/RBV treatment.

Official Title
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A Phase III, Randomised, Double-blind and Placebo Controlled Study of Once Daily BI 201335, 240 mg for 12 or 24 Weeks in Combination With Pegylated interferon-a (PegIFNa) and Ribavirin (RBV) in Patients With Genotype 1 Chronic Hepatitis C Infection Who Failed a Prior PegIFN/RBV Treatment

Conditions
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Hepatitis C, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic hepatitis C genotype 1 infection, diagnosed at least 6 months prior to screening Confirmed prior virological failure with an approved dose of PegIFN/RBV Age 18 to 70 years, HCV RNA (RiboNucleic Acid) = 1,000 IU/mL at screening, Exclusion criteria: HCV infection of mixed genotype; Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV) co-infection Evidence of acute or chronic liver disease due to causes other than chronic HCV infection, Decompensated liver disease, or history of decompensated liver disease, Body weight < 40 or > 125 kg, Clinical evidence of significant or unstable cardiovascular disease, chronic pulmonary disease, history or evidence of retinopathy or clinically significant ophthalmological disorder Pre-existing psychiatric condition that could interfere with the subject's participation in and completion of the study Laboratory parameters disorders (thalassemia major, sickle cell anemia or G6PD deficit) Hemoglobin < 12 g/dL for women and < 13 g/dL for men Patients who have been previously treated with at least one dose of any antiviral or immunomodulatory drug other than interferon alfa or ribavirin for acute or chronic HCV infection including and not restricted to protease or polymerase inhibitors,

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: Placebo/PegIFN/RBV<br>patient to receive two capsules identical to those containing BI201335 once a day for 24 weeks and PegIFN/RBV for 48 weeks | Drug: Pegylated Interferon-alpha (IFN)<br>* Pegylated Interferon-alpha for 48 weeks<br>Drug: Ribavirin (RBV)<br>* Ribavirin (RBV) for 24 or 48 weeks<br>Drug: Placebo<br>* Placebo to BI201335 for 24 weeks<br>|
| Experimental: BI201335 12 weeks<br>patient to receive two capsules containing BI 201335 once a day for 12 weeks and PegIFN/RBV for 48 weeks | Drug: BI 201335<br>* BI 201335 once a day (QD) for 24 weeks<br>Drug: Pegylated Interferon-alpha (IFN)<br>* Pegylated Interferon-alpha for 48 weeks<br>Drug: Ribavirin (RBV)<br>* Ribavirin (RBV) for 24 or 48 weeks<br>|
| Experimental: BI201335 24 weeks<br>patient to receive two capsules containing BI 201335 once a day for 24 weeks and PegIFN/RBV for 48 weeks | Drug: BI 201335<br>* BI 201335 once a day (QD) for 24 weeks<br>Drug: Pegylated Interferon-alpha (IFN)<br>* Pegylated Interferon-alpha for 48 weeks<br>Drug: Ribavirin (RBV)<br>* Ribavirin (RBV) for 24 or 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response 12 Weeks Post Treatment (SVR12) | Percentage of participants with sustained virological response (SVR12) 12 weeks post treatment defined as plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL (undetected) 12 weeks after the originally planned treatment duration. | 12 weeks post treatment, up to 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological Response After 24 Weeks of Treatment Discontinuation (SVR24) | Percentage of participants with virological response after 24 weeks of treatment discontinuation (SVR24) defined as plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL (undetected) 24 weeks after the originally planned treatment duration. | 24 weeks post treatment, up to 72 weeks | 
| Early Treatment Success (ETS) | Percentage of participants with early Treatment Success (ETS) defined as a plasma HCV RNA level <25 IU/mL (undetected or detected) at Week 4 and <25 IU/mL (undetected) at Week 8. | Week 4 and Week 8 | 
| ALT Normalisation: ALT in Normal Range at End of Treatment, When SVR12=NO | The number of participants with alanine aminotransferase (ALT) in normal range at the end of treatment (EoT) when patients do not have sustained virological response 12 weeks post treatment. BL=baseline | End of treatment, up to 48 weeks | 
| ALT Normalisation: ALT in Normal Range at End of Treatment, When SVR12=YES | The number of participants with alanine aminotransferase (ALT) in normal range at the end of treatment when patients have sustained virological response 12 weeks post treatment. BL=baseline | End of treatment, up to 48 weeks | 
| AST Normalisation: AST in Normal Range at End of Treatment, When SVR12=NO | The number of participants with aspartate aminotransferase (AST) in normal range at the end of treatment when patients do not have sustained virological response 12 weeks post treatment. BL=baseline | End of treatment, up to 48 weeks | 
| AST Normalisation: AST in Normal Range at End of Treatment, When SVR12=YES | The number of participants with aspartate aminotransferase (AST) in normal range at the end of treatment (EoT) when patients have sustained virological response 12 weeks post treatment. BL=baseline | End of treatment, up to 48 weeks | 
| ALT Normalisation: ALT in Normal Range 12 Weeks Post Treatment, When SVR12=NO | The number of participants with alanine aminotransferase (ALT) in normal range post treatment when patients do not have sustained virological response 12 weeks post treatment. BL=baseline | 12 weeks post treatment, up to 60 weeks | 
| ALT Normalisation: ALT in Normal Range 12 Weeks Post Treatment, SVR12=YES | The number of participants with alanine aminotransferase (ALT) in normal range post treatment when patients have sustained virological response 12 weeks post treatment. BL=baseline | 12 weeks post treatment, up to 60 weeks | 
| AST Normalisation: AST in Normal Range 12 Weeks Post Treatment, When SVR12=NO | The number of participants with aspartate aminotransferase (AST) in normal range post treatment when patients do not have sustained virological response 12 weeks post treatment. BL=baseline | 12 weeks post treatment, up to 60 weeks | 
| AST Normalisation: AST in Normal Range 12 Weeks Post Treatment, SVR12=YES | The number of participants with aspartate aminotransferase (AST) in normal range post treatment when patients have sustained virological response 12 weeks post treatment. BL=baseline | 12 weeks post treatment, up to 60 weeks |