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

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

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 Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: BI 207127 low dose + SOC; Drug: BI 207127 middle dose +SOC; Drug: BI 207127 high dose+SOC; Drug: Placebo + SOC

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Grenoble cédex 9, France
    • 1241.7.3307A CHU de Grenoble
  • Lille, France
    • 1241.7.3303A Hôpital Claude Huriez
  • Lyon cedex 02, France
    • 1241.7.3302A Hopital de l'Hotel Dieu
  • Montpellier, France
    • 1241.7.3301A Hôpital Saint Eloi
  • Nice Cedex 3, France
    • 1241.7.3305A HOP Archet 2
  • Pessac Cedex, France
    • 1241.7.3306A Hôpital Haut-Lévêque
  • Vandoeuvre, France
    • 1241.7.3304A HOP de Brabois
• Germany
  • Aachen, Germany
    • 1241.7.49010 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1241.7.49012 Boehringer Ingelheim Investigational Site
  • Essen, Germany
    • 1241.7.49004 Boehringer Ingelheim Investigational Site
  • Freiburg, Germany
    • 1241.7.49011 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1241.7.49001 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1241.7.49013 Boehringer Ingelheim Investigational Site
  • Regensburg, Germany
    • 1241.7.49009 Boehringer Ingelheim Investigational Site
  • Ulm, Germany
    • 1241.7.49002 Boehringer Ingelheim Investigational Site
• Switzerland
  • Basel, Switzerland
    • 1241.7.41003 Boehringer Ingelheim Investigational Site
  • Lugano, Switzerland
    • 1241.7.41004 Boehringer Ingelheim Investigational Site
  • St. Gallen, Switzerland
    • 1241.7.41001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 207127 low dose + SOC; BI 207127 low dose tid + SOC	Drug: BI 207127 low dose + SOC; BI 207127 low dose tid + SOC
Experimental: BI 207127 middle dose +SOC; BI 207127 middle dose tid + SOC	Drug: BI 207127 middle dose +SOC; BI 207127 middle dose tid + SOC
Experimental: BI 207127 high dose+SOC; BI 207127 high dose tid +SOC	Drug: BI 207127 high dose+SOC; BI 207127 high dose tid +SOC
Placebo Comparator: Placebo + SOC; Placebo tid +SOC	Drug: Placebo + SOC; Placebo tid +SOC

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Larrey D, Lohse AW, de Ledinghen V, Trepo C, Gerlach T, Zarski JP, Tran A, Mathurin P, Thimme R, Arasteh K, Trautwein C, Cerny A, Dikopoulos N, Schuchmann M, Heim MH, Gerken G, Stern JO, Wu K, Abdallah N, Girlich B, Scherer J, Berger F, Marquis M, Kukolj G, Bocher W, Steffgen J. Rapid and strong antiviral activity of the non-nucleosidic NS5B polymerase inhibitor BI 207127 in combination with peginterferon alfa 2a and ribavirin. J Hepatol. 2012 Jul;57(1):39-46. doi: 10.1016/j.jhep.2012.02.015. Epub 2012 Mar 10.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: May 19, 2009
• First Submitted That Met QC Criteria: May 19, 2009
• First Posted (Estimate): May 20, 2009

Study Record Updates

• Last Update Posted (Estimate): April 19, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: 1241.7; 2008-008292-34 (EudraCT Number: EudraCT)