Study of PPI-668, BI 207127 and Faldaprevir, With and Without Ribavirin, in the Treatment of Chronic Hepatitis C

Study Overview
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Brief Summary
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This study is designed to provide a preliminary assessment of the safety and effectiveness of the combination of PPI-668, BI 207127 and faldaprevir, with or without ribavirin, in the treatment of chronic hepatitis C virus infection.

Official Title
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A Phase 2a Study of PPI-668 in Combination With BI 207127 and Faldaprevir, With and Without Ribavirin, in Treatment-Naive Patients With Chronic Hepatitis C (HCV Genotype 1a)

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: PPI-668
* Drug: BI 207127 Dose 1
* Drug: BI 207127 Dose 2
* Drug: Faldaprevir
* Drug: Ribavirin
* Drug: BI 207127 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 to 65 years of age; if females are of childbearing potential, then they must be willing to use two non-hormonal methods of birth control Body weight greater than 40 kg and less than 125 kg Clinical diagnosis of chronic hepatitis C Treatment-naïve for hepatitis C: no previous treatment with interferon, pegylated interferon, ribavirin, telaprevir, boceprevir, or any investigational therapies for hepatitis C No symptoms or signs of intercurrent illness at Screen (other than those attributable to hepatitis C) No clinically significant abnormalities in the 12-lead electrocardiogram at Screen Signed informed consent prior to trial participation. Exclusion Criteria: Seropositive for HIV antibody or Hepatitis B Surface Antigen at Screen Liver disease due to causes other than chronic HCV infection Symptoms or signs of decompensated liver disease, or evidence of cirrhosis Any medical condition that may interfere with the absorption, distribution or elimination of study drugs Poorly controlled or unstable hypertension at Screen. Clinically significant, unstable cardiovascular or pulmonary disease, including cardiovascular or pulmonary disease requiring pharmacologic intervention other than anti-hypertensive medications, statins, and/or prophylactic aspirin (or similar anticoagulant). Red blood cell disorder, including (but not limited to): thalassemia major or minor, sickle cell anemia. Diabetes Mellitus treated with insulin or hypoglycemic agents History of asthma requiring hospital admission within the preceding 12 months History of alcohol abuse or illicit drug use which could interfere with a patient's compliance with the protocol requirements, or with the safety or efficacy assessments in this study Patients requiring treatment, during this study, with any of the medications on the restricted medications list (provided in the investigator site file), are not eligible for this study due to considerations of possible drug interactions with the study drug regimen.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PPI-668, BI 207127 Dose 1, Faldaprevir, and Ribavirin<br>PPI-668, BI 207127 Dose 1, Faldaprevir, and Ribavirin dosed in combination | Drug: PPI-668<br> <br> Drug: BI 207127 Dose 1<br> <br> Drug: Faldaprevir<br> <br> Drug: Ribavirin<br> <br> |
| Active Comparator: PPI-668, BI 207127 Dose 2, Faldaprevir, and Ribavirin<br>PPI-668, BI 207127 Dose 2, BI 207127 Placebo, Faldaprevir, and Ribavirin dosed in combination | Drug: PPI-668<br> <br> Drug: BI 207127 Dose 2<br> <br> Drug: Faldaprevir<br> <br> Drug: Ribavirin<br> <br> Drug: BI 207127 Placebo<br> <br> |
| Active Comparator: PPI-668, BI 207127 Dose 1, and Faldaprevir<br>PPI-668, BI 207127 Dose 1, and Faldaprevir dosed in combination | Drug: PPI-668<br> <br> Drug: BI 207127 Dose 1<br> <br> Drug: Faldaprevir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the proportion of patients achieving sustained viral response (SVR) |  | 12 weeks after the end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with virologic relapse post-treatment, defined as confirmed and quantifiable (>LLOQ) serum HCV RNA in a patient who achieved non-detectable serum HCV RNA by the end of treatment |  | up to 24 weeks post-treatment | 
| Proportion of patients with confirmed viral breakthrough during study treatment | Confirmed viral breakthrough is defined as a > 1 log increase in HCV RNA from post-Baseline nadir value or confirmed increase in HCV RNA ≥LLOQ if HCV RNA previously declined to <LLOQ (detected or not detected), during the 12-week study treatment period | up to 12 weeks of study treatment | 
| Proportions of study participants who receive at least one dose of study drug and who prematurely discontinue study treatment, and proportions prematurely discontinuing treatment for clinical adverse events or laboratory abnormalities |  | up to 12 weeks of study treatment | 
| Proportions of study participants experiencing treatment-emergent adverse events (serious and non-serious) considered to be possibly or probably attributable to study treatment, overall and by body system |  | up to 12 weeks of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver diseases, Virus diseases, Ribavirin, protease inhibitor, NS5B polymerase inhibitor, NS5A inhibitor