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

Boehringer Ingelheim75 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Hepatitis C, Chronic

Interventions

BI 207127 middle dose +SOCDRUG

BI 207127 middle dose tid + SOC

BI 207127 high dose+SOCDRUG

BI 207127 high dose tid +SOC

Placebo + SOCDRUG

Placebo tid +SOC

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion criteria: 1. HCV genotype 1 2. HCV viral load \>100,000 IU/mL 3. histology or fibroscan to rule out cirrhosis 4. Absence of retinopathy 5. treatment naive patients and treatment experienced patients 6. Age 18 - 70 years 7. Male OR female with documented hysterectomy OR postmenopausal Exclusion criteria: 1. Fertile males not willing to use an adequate form of contraception 2. Pretreatment with any HCV-polymerase inhibitor 3. Any concurrent disease if clinically significant based on the investigator's medical assessment 4. Current alcohol or drug abuse, or history of the same 5. Positive test for HIV or HBs 6. History of malignancy 7. Planned or concurrent usage of any other pharmacological therapy including any antiviral therapy or vaccination 8. Usage of any investigational drug within thirty (30) days prior to enrolment or 5 halflives, whichever is longer 9. Any clinically significant laboratory abnormalities based on the investigator's medical assessment at screening 10. Patients treated with any interferon (approved or investigational) or Peg-IFN and/or Ribavirin within 3 months prior to screening 11. Known hypersensitivity to drugs or excipients; Further exclusion criteria apply

Locations (18)

1241.7.3307A CHU de Grenoble

Grenoble Cédex 9, France

1241.7.3303A Hôpital Claude Huriez

Lille, France

Outcomes

Primary Outcomes

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.

Time frame: Baseline and 4 weeks

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 4 weeks

Data from ClinicalTrials.gov

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BI 207127 low dose tid + SOC

1241.7.3302A Hopital de l'Hotel Dieu

Lyon, France

1241.7.3301A Hôpital Saint Eloi

Montpellier, France

1241.7.3305A HOP Archet 2

Nice, France

1241.7.3306A Hôpital Haut-Lévêque

Pessac, France

1241.7.3304A HOP de Brabois

Vandœuvre-lès-Nancy, France

1241.7.49010 Boehringer Ingelheim Investigational Site

Aachen, Germany

1241.7.49012 Boehringer Ingelheim Investigational Site

Berlin, Germany

1241.7.49004 Boehringer Ingelheim Investigational Site

Essen, Germany

...and 8 more locations

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)

Time frame: 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.

Time frame: 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).

Time frame: Until end of treatment, up to 570 days

Plasma Concentration Time Profiles of BI 207127

Plasma concentration time profiles of BI 207127

Time frame: 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

Time frame: 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

Time frame: 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).

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

Time frame: 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.

Time frame: 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).

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 4 weeks