Safety, Antiviral Activity and PK of MRD of BI 201335 in Chronic Hepatitis C Patients Both Treatment Naive and -Experienced

Boehringer Ingelheim96 enrolled

Overview

This study will investigate safety, antiviral activity, and pharmacokinetics of BI 201335 NA in HCV genotype 1 infected patients treated for 14 days monotherapy followed by BI 201335 NA combination therapy with PegIFN/RBV for an additional 14 days for treatment-naïve patients; or for 28 days as BI 201335 NA combination therapy with PegIFN/RBV for treatment-experienced patients. A secondary objective is to investigate antiviral activity, potential drug-drug interactions and safety of combination therapy of BI 201335 NA and PegIFN/RBV up to 28 days for treatment-naïve patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Hepatitis C, Chronic

Interventions

BI201335

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: 1a. For treatment-naïve patients: no prior therapy with interferon, peginterferon, or ribavirin for acute or chronic hepatitis C infection 1b. For treatment-experienced patients: confirmed virological failure during or after combination treatment with an approved dose of alfa-2a or alfa-2b peginterferon combined with ribavirin; such patients must have received at least 12 weeks of therapy with a 90 day washout period prior to screening and must have documentation of medical history prior to enrolment in 1220.2 2. Age 18 years or older 3. Signed informed consent form prior to trial participation 4. Male or female with documented hysterectomy or menopausal female with last menstrual period at least 6 months prior to screening 5. Chronic hepatitis C infection of genotype 1, diagnosed by positive HCV serology test (HCV Ab positive) or detectable HCV RNA at least 6 months prior to screening 6. HCV viral load \>= 100,000 IU/mL at screening 7. TSH and T4 within normal limits or adequately controlled thyroid function 8. Histological evidence within 36 months prior to study enrolment of any degree of chronic necroinflammatory activity or the presence of fibrosis (Ishak Grade 1-4 or Metavir Grade 1-3) Exclusion criteria: 1. Patients who have been previously treated with at least one dose of any protease inhibitor for acute or chronic hepatitis C infection 2. Evidence of liver disease due to causes other than chronic HCV infection 3. Positive ELISA for HIV-1 or HIV-2 4. Hepatitis B virus (HBV) infection based on presence of Hbs Ag or HBV DNA 5. Any previous liver biopsy consistent with cirrhosis 6. Decompensated liver diseases as evidenced by ascites, portal hypertension, jaundice or hepatic encephalopathy 7. Haemophilia 8. Hemoglobinopathy (e.g., thalassemia major or sickle cell anemia) 9. Severe pre-existing psychiatric disease 10. Poorly controlled diabetes mellitus 11. Ischaemic heart disease 12. Chronic obstructive airway disease 13. Autoimmune disease; including autoimmune hepatitis 14. History of alcohol abuse within the past 12 months 15. Hyperbilirubinemia (conjugated bilirubin) \>1.5x ULN 16. Alkaline phosphatase \>1.5x ULN 17. ALT and AST levels \>= 5 x ULN 18. Hemoglobin \< 12.0 g/dL for women and \< 13.0 g/dL for men 19. White blood cell count \< 2000 cells/mm3 20. Absolute Neutrophil Count \< 1500 cells/mm3 21. Platelet count \< 100,000 cells/mm3 22. Prothrombin time INR (Institutional Normalized Ratio) prolonged to \> 1.5 x ULN 23. Usage of any investigational drug within 30 days prior to enrolment; or the planned usage of an investigational drug during the course of the current study 24. Known hypersensitivity to study drugs

Locations (16)

1220.2.10 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

1220.2.15 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

1220.2.17 Boehringer Ingelheim Investigational Site

Baltimore, Maryland, United States

1220.2.11 Boehringer Ingelheim Investigational Site

New York, New York, United States

1220.2.12 Boehringer Ingelheim Investigational Site

New York, New York, United States

1220.2.14 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

1220.2.3304A Boehringer Ingelheim Investigational Site

Lyon, France

1220.2.3303A Boehringer Ingelheim Investigational Site

Marseille, France

1220.2.3301A Boehringer Ingelheim Investigational Site

Paris, France

1220.2.3302A Boehringer Ingelheim Investigational Site

Paris, France

...and 6 more locations

Outcomes

Primary Outcomes

Efficacy: VR (Virologic Response) of >=2 log10 Reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Any Time up to Day 14 (naïve Patients) or Day 28 (Experienced Patients)

Efficacy endpoint: VR (virologic response) of \>=2 log10 reduction in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) from baseline at any time up to Day 14 (naïve patients) or Day 28 (experienced patients).

Time frame: Baseline and up to 4 weeks

Occurrence of Adverse Events (AEs) During BI201335 + Washout Period

Occurrence of Adverse Events (AEs) during BI201335 + washout period. For placebo patients include all AEs through 30 days after trial discontinuation.

Time frame: from day 1 and up to 4 weeks + 4 days washout

Occurrence of Serious Adverse Events (SAEs) During BI201335 + Washout Period

Occurrence of Serious Adverse Events (SAEs)during BI201335 or BI201335+ washout period. For placebo patients include all SAEs through 30 days after trial discontinuation.

Time frame: from day 1 and up to 4 weeks + 4 days washout

Occurrence of Laboratory Test Abnormalities and With Respect to Division of AIDS (DAIDS) Classification and Laboratory Test Values Change Over Time

Occurrence of laboratory test abnormalities and with respect to Division of AIDS (DAIDS) classification and laboratory test values change over time. ALT=Alanine transaminase (SGPT), AST=Aspartate transaminase (SGOT).

Time frame: Baseline and up to 4 weeks

Secondary Outcomes

Maximum Viral Load Reduction From Baseline up to Day 14 for Treatment-naïve Patients and Day 28 Treatment for Treatment-experienced Patients

Maximum viral load reduction from baseline up to Day 14 for treatment-naïve patients and Day 28 treatment for treatment-experienced patients.

Time frame: Baseline and up to 4 weeks

Change From Baseline in Viral Load on Day 14 for Treatment-naïve Patients and on Day 28 Treatment for Treatment-experienced Patients

Change from baseline in viral load on Day 14 for treatment-naïve patients and on Day 28 treatment for treatment-experienced patients.

Time frame: Baseline and up to 4 weeks

Rapid Virologic Response (RVR)

Rapid virologic response (RVR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) on Day 28 for all patients.

Time frame: week 4

Early Virologic Response (EVR)

Early Virologic Response (EVR): \>=2 log10 reduction in plasma HCV RNA level from baseline at week 12 (day 84)

Time frame: week 12

Complete EVR1 (cEVR1)

VL (Viral load) below the limit of quantification of the Roche COBAS Taqman HCV/HPS assay (25 IU/mL) at 4 weeks and below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at 12 weeks

Time frame: week 4 and week 12

Complete EVR2 (cEVR2)

VL below the limit of detection at both 4 weeks and 12 weeks

Time frame: week 4 and week 12

End of Treatment Response (ETR)

End of Treatment Response (ETR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at week 48 (Day 336).

Time frame: week 48

Sustained Virologic Response (SVR)

Sustained Virologic Response (SVR): Plasma HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) at week 72 (Day 504).

Time frame: week 72

Achievement of an HCV RNA Level Below the Limit of Detection Over Time

Achievement of an HCV RNA level below the limit of detection of the Roche COBAS Taqman HCV/HPS assay (10 IU/mL) over time

Time frame: from day 1 and up to 4 weeks

Achievement of an HCV RNA Level Below the Limit of Quantification Over Time

Achievement of an HCV RNA Level Below the Limit of quantification of the Roche COBAS Taqman HCV/HPS assay (25 IU/mL) Over Time

Time frame: from day 1 and up to 4 weeks

Achievement of a >= 2 log10 Reduction in Plasma HCV RNA Level From Baseline Over Time

Achievement of a \>= 2 log10 reduction in plasma HCV RNA level from baseline over time.

Time frame: from day 1 and up to 4 weeks

Occurrence of AEs, by Action Taken With Regard to Study Medication

Occurrence of AEs, by action taken with regard to study medication.

Time frame: from day 1 and up to 4 weeks

Occurrence of Discontinuations Due to AEs During BI201335 or BI201335+PegIFN/RBV Combination Treatment Period

Occurrence of discontinuations due to AEs during BI201335 or BI201335+PegIFN/RBV combination treatment period.

Time frame: from day 1 and up to 4 weeks

PK (Pharmacokinetic) Parameter After the First Dose: Cmax ( Maximum Measured Concentration of the Analyte in Plasma)

PK (pharmacokinetic) parameter after the first dose: Cmax ( Maximum measured concentration of the analyte in plasma ). .

Time frame: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)

PK Parameter After the First Dose: Tmax (Time From (Last) Dosing to the Maximum Measured Concentration of the Analyte in Plasma)

PK parameter after the first dose: tmax (Time from (last) dosing to the maximum measured concentration of the analyte in plasma).

Time frame: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)

PK Parameter After the First Dose: AUCτ,1 (Area Under the Concentration-time Curve of the Analyte in Plasma Over a Uniform Dosing Interval τ on Day 1)

PK parameter after the first dose: AUCτ,1 (Area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ on day 1).

Time frame: Times of -0:15, 0:30, 1:00, 2:00, 3:00, 4:00, 6:00. 8:00. 12:00, and 16:00 h relative to first administration of trial medication (on day 1)

PK Parameter at Steady State After the Last Dose: Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State Over a Uniform Dosing Interval τ)

PK parameter at steady state after the last dose: Cmax,ss (Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ).