4 Week Combination of BI 207127 NA With Peg-IFN and Ribavirin in Chronic HCV Patients

Study Overview
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Brief Summary
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The main purpose of this clinical trial with BI 207127 is to see the effect of 4 week combination of BI 207127 with Peginterferon alfa (Peg-IFN) and Ribavirin (RBV) on hepatitis C virus (HCV) virus load and how safe BI 207127 is in this combination in HCV infected patients.

Official Title
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Safety, Antiviral Activity, and Pharmacokinetics of BI 207127 NA Administered in Combination With Peg-IFN and Ribavirin in Chronic HCV-infected Patients for 4 Weeks, a Randomised, Double-blind, Placebo Controlled Study

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: BI 207127 middle dose +SOC
* Drug: BI 207127 high dose+SOC
* Drug: Placebo + SOC
* Drug: BI 207127 low dose + SOC


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: HCV genotype 1 HCV viral load >100,000 IU/mL histology or fibroscan to rule out cirrhosis Absence of retinopathy treatment naive patients and treatment experienced patients Age 18 - 70 years Male OR female with documented hysterectomy OR postmenopausal Exclusion criteria: Fertile males not willing to use an adequate form of contraception Pretreatment with any HCV-polymerase inhibitor Any concurrent disease if clinically significant based on the investigator's medical assessment Current alcohol or drug abuse, or history of the same Positive test for HIV or HBs History of malignancy Planned or concurrent usage of any other pharmacological therapy including any antiviral therapy or vaccination Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer Any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening Patients treated with any interferon (approved or investigational) or Peg-IFN and/or Ribavirin within 3 months prior to screening Known hypersensitivity to drugs or excipients; Further exclusion criteria apply

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 |
| --- | --- |
| Experimental: BI 207127 low dose + SOC<br>BI 207127 low dose tid + SOC | Drug: BI 207127 low dose + SOC<br>* BI 207127 low dose tid + SOC<br>|
| Experimental: BI 207127 middle dose +SOC<br>BI 207127 middle dose tid + SOC | Drug: BI 207127 middle dose +SOC<br>* BI 207127 middle dose tid + SOC<br>|
| Experimental: BI 207127 high dose+SOC<br>BI 207127 high dose tid +SOC | Drug: BI 207127 high dose+SOC<br>* BI 207127 high dose tid +SOC<br>|
| Placebo Comparator: Placebo + SOC<br>Placebo tid +SOC | Drug: Placebo + SOC<br>* Placebo tid +SOC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Virologic Response Defined as >= 3 Log Drop in Viral Load From Baseline at Day 28 With no Evidence of Virologic Rebound During These 28 Days. Virologic Rebound is Defined as >= 1 Log Increase in Viral Load From Nadir. | The primary efficacy endpoint is the number of participants with virologic response defined as >= 3 log drop in viral load from baseline at day 28 with no evidence of virologic rebound during these 28 days. Virologic rebound is defined as >= 1 log increase in viral load from nadir. | Baseline and 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral Load (Log10) at Each Visit up to Day 28, Change From Baseline | Reductions of viral load (Log10) at each visit up to day 28, change from baseline. Change from baseline was calculated as the value at baseline minus the value at each later visit. A negative value represents an increase in viral load, a positive value represents a decrease in viral load. | Baseline and days 1, 2, 4, 8, 15, 22 and 28 | 
| Viral Load at Each Visit up to Day 28 | Viral load (VL) (original values) at each visit up to day 28. | Baseline and days 8, 15, 22 and 28 | 
| Number of Participants With Virologic Response at Day 28 | Number of participants with virologic response at day 28, defined as achieving viral load below the limit of quantification (BLQ), <10 IU/mL, at day 28 | day 28 | 
| Number of Participants With Rapid Virological Response | Number of participants with rapid virological response - defined as serum Hepatitis C virus (HCV) RNA level below the limit of detection (BLD) of the Roche COBAS Taqman HCV/High Pure System (HPS) for extraction assay (10 IU/mL) on Day 28. | 4 weeks | 
| Number of Participants With Early Virological Response | Number of participants with early virological response (EVR) defined as at least 2log10 reduction in HCV Ribonucleic acid (RNA) from baseline at Week 12. Number of responders* - Response = At least a 2 log10 reduction in viral load from baseline at Week 12 (Day 84) | Baseline and week 12 | 
| Number of Participants With End of Treatment Response | Number of participants with end of treatment response (ETR) - defined as serum HCV RNA level below the limit of detection (BLD) of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at end of treatment (including 5-day washout). Number of responders* - Response = Viral load below the limit of detection at end of all treatment. | Week 12 | 
| Number of Participants With Sustained Virological Response | Number of participants with sustained virological response. Sustained virological response was defined as serum HCV RNA below the limit of detection (<10 IU/mL) at least 85 days after stopping standard care (SOC). | Until end of treatment, up to 570 days | 
| Plasma Concentration Time Profiles of BI 207127 | Plasma concentration time profiles of BI 207127 | 0.5 hours (h), 3h, 8h, 15h, 23.917h, 503.917h, 649h, 652h, 656h and 672h after drug administration | 
| Plasma Concentration Time Profiles of CD 6168 | Plasma concentration time profiles of CD 6168 | 0.5 hours (h), 3h, 8h, 15h, 23.917h, 503.917h, 649h, 652h, 656h and 672h after drug administration | 
| Cmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State) | Maximum measured concentration of the analyte in plasma (Cmax) after first dose on day 1 (Cmax) and after last dose (steady state) on day 28 (Cmax,ss) of BI 207127 and CD 6168 | 5 min before drug admin and 30min, 1 hour (h), 2h, 3h, 4h, 5h 55min, 8h, 10h, 11h 55min and 15h after drug administration on day 1: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28 | 
| Tmax of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State) | tmax [h] Time from (last) dosing to the maximum measured concentration of the analyte in plasma after first dose on day 1 and after last dose on day 28 (steady state). | 5 min before drug admin and 30min, 1 hour (h), 2h, 3h, 4h, 5h 55min, 8h, 10h, 11h 55min and 15h after drug administration on day 1: 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28 | 
| AUC0-6 of BI 207127 and CD 6168 in Plasma After First Dose and After Last Dose (Steady State) | Area under the concentration-time curve of the analyte in plasma (AUC) after first dose on day 1 (AUC0-6) and after last dose on day 28 (AUC0-6,ss) of BI 207127 and CD 6168 | 30min, 1 hour (h), 2h, 3h, 4h and 5h 55min after drug administration on day 1: 30min, 1h, 2h, 3h, 4h and 6h after admin on day 28 | 
| Cpre Pharmacokinetic Parameter of BI 207127 and CD 6168 | Cpre,N [ng/mL] - Predose concentration of the analyte in plasma immediately before administration of the Nth dose after N-1 doses were administered for BI 207127 and CD 6168. Descriptive statistics were calculated only if at least 2/3 plasma concentrations were available. All values for Cpre,1 were not available, therefore no results are presented below. | 5 minutes before drug administration on days 1, 2, 4, 8, 15, 22 and 27 | 
| C6,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose | C6,ss Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose. C6,ss is the concentration 6 hours after dosing at steady-state (reported as 654 h). | 654 hours after drug administration on day 28 | 
| AUC0-infinity,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose | Area under the concentration time curve of the analyte in plasma over the time interval of 0 to infinity at steady state (AUC0-infinity,ss): Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State (SS) After the Last Dose | 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28 | 
| λz Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose | Terminal rate constant in plasma (λz): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose | 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28 | 
| t1/2,ss and MRTpo,ss Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose | Terminal half-life of the analyte in plasma at steady state (t1/2,ss) and mean residence time of the analyte in the body at steady state after oral administration (MRTpo,ss): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose | 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28 | 
| RA,Cmax Pharmacokinetic Parameters of BI 207127 and CD 6168 at Steady State After the Last Dose | Accumulation ratio of maximum measured concentration of the analyte in plasma (RA,Cmax): Pharmacokinetic parameters of BI 207127 and CD 6168 at steady state after the last dose. Ratio was calculated as Cmax,ss divided by Cmax. | 5 min before drug admin and 30min, 1h, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h and 48h after admin on day 28 | 
| Number of Participants With Clinical Relevant Abnormalities for Vital Signs, Body Temperature, Physical Examination, Blood Chemistry, Haematology, Coagulation, Urinalysis and ECG | Number of participants with clinically relevant abnormalities for vital signs, blood chemistry, body temperature, physical examination, haematology, coagulation, urinalysis and electrocardiography (ECG). New abnormal findings or worsening of baseline conditions were reported as adverse events. | From the start of the study to Day 30 (2 days after last dose) | 
| Number of Participants With Discontinuations Due to AEs | Number of participants with adverse events (AEs) leading to discontinuation of trial drug | 4 weeks |