Phase 3 Study of BI 207127 in Combination With Faldaprevir and Ribavirin for Treatment of Patients With Hepatitis C Infection, Including Patients Who Are Not Eligible to Receive Peginterferon: HCVerso2

Study Overview
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Brief Summary
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The aim of the study is to confirm efficacy and safety of treatment with 600 mg of BID BI 207127 in combination with 120 mg QD FDV and RBV for 16 or 24 weeks in target chronically infected HCV GT1b treatment naïve patients, including patients with compensated cirrhosis.

Official Title
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A Phase III Randomised, Partially Double-blind and Placebo-controlled Study of BI 207127 in Combination With Faldaprevir and Ribavirin for Chronic Genotype 1 Hepatitis C Infection in an Extended Population of Treatment naïve Patients That Includes Those Ineligible to Receive Peginterferon

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: BI 207127-placebo: 8-week treatment
* Drug: Ribavirin: 24-week treatment
* Drug: BI 207127: 24-week treatment
* Drug: Faldaprevir: 24-week treatment
* Drug: Faldaprevir: 24-week treatment
* Drug: Ribavirin-placebo: 8-week treatment
* Drug: BI 207127: 24-week treatment
* Drug: Faldaprevir-placebo: 8-week treatment
* Drug: Faldaprevir: 16-week treatment
* Drug: Ribavirin: 16-week treatment
* Drug: RBV: 24-week treatment
* Drug: BI 207127: 16-week treatment


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 HCV infection of sub-GT1b confirmed by genotypic testing at screening. HCV viral load =1,000 IU/mL at randomisation. Patients who have never been previously treated with any other HCV treatment regimen. Exclusion criteria: HCV infection of mixed GT (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening. HCV infection of sub-GT1a, mixed GT1a/1b, or undefined GT1. Liver disease due to causes other than chronic HCV infection. HIV infection. Hepatitis B virus infection based on presence of HBs-Ag. Confirmed or suspected active malignancy or history of malignancy within the last 5 years prior to screening. History of illicit drug abuse other than cannabis or chronic alcohol abuse within 12 months prior to randomisation. Subject is not willing to comply with the precautionary measures to prevent photosensitivity (avoid excessive sun exposure and use sun block on a daily basis). Decompensated liver disease, or history of decompensated liver disease. Clinical evidence of unstable cardiovascular disease which may further decompensate due to anemia. Red blood cell disorders. Body weight <40 kg or >125 kg.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomised 24-week arm<br>BI 207127 in combination with FDV and RBV for 24 weeks (randomised) | Drug: BI 207127: 24-week treatment<br>* 24 weeks of active treatment<br>Drug: Faldaprevir: 24-week treatment<br>* 24 weeks of active treatment<br>Drug: RBV: 24-week treatment<br>* 24 weeks of active treatment<br>|
| Experimental: Randomised 16-week arm<br>BI 207127-placebo, FDV-placebo and RBV-placebo for 8 weeks followed by BI 207127 in combination with FDV and RBV for 16 weeks (randomised) | Drug: BI 207127-placebo: 8-week treatment<br>* 8 weeks of placebo treatment<br>Drug: Ribavirin-placebo: 8-week treatment<br>* 8 weeks of placebo treatment<br>Drug: Faldaprevir-placebo: 8-week treatment<br>* 8 weeks of placebo treatment<br>Drug: Faldaprevir: 16-week treatment<br>* 16 weeks of active treatment<br>Drug: Ribavirin: 16-week treatment<br>* 16 weeks of active treatment<br>Drug: BI 207127: 16-week treatment<br>* 16 weeks of active treatment<br>|
| Experimental: Allocated 24-week arm<br>BI 207127 in combination with FDV and RBV for 24 weeks (allocated to patients with compensated cirrhosis) | Drug: Ribavirin: 24-week treatment<br>* 24 weeks of active treatment<br>Drug: Faldaprevir: 24-week treatment<br>* 24 weeks of active treatment<br>Drug: BI 207127: 24-week treatment<br>* 24 weeks of active treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR12 Rates With Historical Control | Sustained Virologic Response at Week 12 post-treatment (SVR12): Plasma Hepatitis C virus (HCV) RNA level <25 IU/mL at 12 weeks after end of Treatment (EOT). SVR12, was assessed based on the observed HCV RNA result taken at least 10 weeks after treatment discontinuation. This definition was also applied to patients who discontinued treatment early: if the patient had HCV RNA undetected at least 10 weeks after stopping all treatment, they were considered a responder in the primary analysis. This is the primary analyses of the primary endpoint. The number of participants analyzed are actually adjusted number of participant analyzed. | 12 Week (post-treatment) | 
| Comparisons of SVR12 Rates Across Treatment Arms | Sustained Virologic Response rates across treatment arms at Week 12 post-treatment (SVR12). This is the secondary analyses of the primary endpoint. | 12 Week (post-treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR4: Plasma HCV RNA Level <25 IU/mL at 4 Weeks After EOT. | Sustained Virologic Response rates across treatment arms at Week 4 post-treatment (SVR4): Plasma HCV RNA level <25 IU/mL at 4 weeks after EOT. | 4 weeks (after End Of Treatment) | 
| SVR24: Plasma HCV RNA Level <25 IU/mL at 24 Weeks After EOT. | Sustained Virologic Response rates across treatment arms at Week 24 post-treatment (SVR24): Plasma HCV RNA level <25 IU/mL at 24 weeks after EOT. | 4 weeks (after End Of Treatment) | 
| Prognostic Value of SVR12 Predicting SVR24 | The positive predictive value of SVR12 predicting SVR24 are the patients with an SVR12 (=YES) and the SVR24 was assessed. | 24 Week (post-treatment) |