Phase III Trial of BI 201335 (Faldaprevir) in Treatment Naive (TN) and Relapser Hepatitis C Virus (HCV)-Human Immunodeficiency Virus (HIV) Coinfected Patients (STARTverso 4)

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 24-48 weeks, according to re-randomisation of Early Treatment Success (ETS) patients at 24 weeks to stop PegIFN/RBV or continue PegIFN/RBV until week 48. If no ETS, then PegIFN/RB for 48 weeks, in HCV treatment-naive or relapsers patients coinfected with HIV

Official Title
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Safety and Efficacy of 120mg and 240mg BI 201335 Once Daily in Combination With Pegylated Interferon Alpha and Ribavirin for Treatment of Chronic Hepatitis C (HCV) Genotype 1 Infection in HIV/HCV Co-infected Patients. A Multinational, Randomised, Parallel Group, Open-label Trial.

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: PegIFN/RBV
* Drug: PegIFN/RBV
* Drug: BI201335
* Drug: BI201335 24W
* Drug: PegIFN/RBV
* Drug: Bi 201335


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chronic hepatitis C (HCV) genotype 1 infection Chronic Human Immunodeficiency Virus (HIV) -1 infection HCV treatment naive or HCV treatment experienced but only relapsers Age 18 to 70 years Antiretroviral treatment naive or on stable Highly Active Antiretroviral Therapy (HAART) Karnofsky score >70 HCV viral load >1.000 IU/mL Exclusion criteria: HCV infection of mixed genotype (1/2, 1/3, 1/4) Evidence of acute or chronic liver due to chronic HCV infection Hepatitis B virus (HBV) infection with presence of HBs-Ag Active malignancy or history or malignancy within the last 5 years Received concomitant systemic antiviral (other than antiretroviral), hematopoietic growth factor or immunomodulatory treatment in 28 days prior enrolment. Decompensated liver disease,as evidenced by ascites, hepatic encephalopathy, esophageal variceal bleeding, and/or laboratory values that add up to >/= 7 points according tho the Child-Turcotte-Pugh classification Hemoglobin </=11g/dL for women and </= 12 g/dL for men Patients with stable cardiac disease and Hemoglobin <12g/dL Known hypersensitivity to any ingredient of the study drugs

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI201335 12W<br>patient to receive two capsules of BI 201335 once a day for 12 weeks and pegIFN/RBV for 24 or 48 weeks | Drug: PegIFN/RBV<br>* PegIFN/RBV for 24 or 48w<br>Drug: BI201335<br>* BI201335 for 12w<br>|
| Experimental: BI 201335 24W<br>patient to receive two capsules of BI 201335 once a day for 24 weeks and PegIFN/RBV for 24 or 48 weeks | Drug: BI201335 24W<br>* BI201335 for 24w<br>Drug: PegIFN/RBV<br>* PegIFN/RBV for 24 or 48w<br>|
| Experimental: BI 201335 24 W<br>patient to receive one capsule of BI 201335 once a day for 24 weeks and pegIFN/RBV for 24 or 48 weeks | Drug: PegIFN/RBV<br>* PegIFN/RBV for 24 or 48w<br>Drug: Bi 201335<br>* BI 201335 for 24 w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response (SVR12) | Percentage of participants with sustained Virological Response SVR12: Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) level <25 IU/mL, undetected 12 weeks after the planned end of treatment. | 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological Response 24 Weeks Post Treatment (SVR24) | Percentage of participants with virological response 24 weeks post treatment (SVR24): Plasma HCV RNA level<25IU/mL (undetected) 24 weeks after the planned end of treatment. | 72 weeks | 
| Early Treatment Success (ETS) | Early Treatment Success (ETS): Plasma HCV RNA level<25 IU/mL (detected or undetected) at Week 4 and HCV RNA< 25 IU/mL, undetected at Week 8 | Week 4, week 8 and week 60 | 
| The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment (EoT) When SVR12=Yes | The number of participants with Alanine Aminotransferase (ALT) normalisation at End of Treatment (EoT) when SVR12=yes. BL stands for baseline. | 48 weeks | 
| The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment When SVR12=no | The number of participants with Alanine Aminotransferase (ALT) normalisation: ALT in normal range at End of Treatment when SVR12=no. BL stands for baseline. | 48 weeks | 
| The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=Yes | The number of participants with ALT in normal range at post treatment (SVR12 Visit) when SVR12=yes. BL = baseline. | 60 weeks | 
| The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=no | The number of participants with ALT in normal range at post treatment (SVR12 Visit) when SVR12=no. BL = baseline. | 60 weeks | 
| The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=Yes | The number of participants with Aspartate Aminotransferase (AST) normalisation at End of Treatment when SVR12=yes. BL = baseline. | 48 weeks | 
| The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=no | The number of participants with Aspartate Aminotransferase (AST) normalisation at End of Treatment when SVR12=no. BL = baseline. | 48 weeks | 
| The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=Yes | The number of participants with AST in normal range at Post Treatment (SVR12 Visit) when SVR12=yes. BL = baseline. | 60 weeks | 
| The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=no | The number of participants with AST in normal range at Post Treatment (SVR12 Visit) when SVR12=no. BL = baseline. | 60 weeks |