Clinical trial NCT00774397: Antiviral Effect, Safety, and Pharmacokinetics of BI201335 +PegIFN/RBV in HCV-GT1 (SILEN-C1&2)
Official title: Antiviral Effect, Safety and Pharmacokinetics of BI 201335 NA in Hepatitis C Virus Genotype 1 Infected Treatment-naïve and Treatment-experienced Patients for 24 Weeks as Combination Therapy With Pegylated Interferon-alpha 2a and Ribavirin (Double-blinded, Randomised, Placebo-controlled, Phase II)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-10-17
Enrollment: 719
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective was to investigate the antiviral effect, safety, and pharmacokinetics of BI 201335 (Faldaprevir), given as a soft gelatine capsule, in patients with hepatitis C virus (HCV) genotype 1 infection. Combination therapy of BI 201335 (Faldaprevir) with pegylated interferon α-2a (PegIFN) and ribavirin (RBV), with or without a 3-day lead-in, was assessed in treatment-naïve (TN) and treatment experienced (TE) patients.


Eligibility criteria: Inclusion criteria:

chronic HCV GT1; therapy-naive to IFN, PegIFN, or RBV; HCV VL \>=100,000 IU/mL Liver biopsy within 2 years prior to study enrolment showing necroinflammatory activity or presence of fibrosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 age 18-65 years Females and males with adequate contraception

Exclusion criteria:

Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection HIV-1 or HIV-2 positive HBV positive Decompensated liver disease, or history of decompensated liver disease Active or suspected malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse within the past 12 months. Usage of any investigational drug within 30 days prior to enrolment, or 5 half-lives, whichever is longer Known hypersensitivity to any ingredient of the study drugs Condition that is defined as one which in the opinion of the investigator may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study Alpha-fetoprotein value \> 100ng/mL at screening; if \>20ng/mL and \<=100ng/mL, patients can be included if there is no evidence of liver cancer in two congruent imaging studies Total bilirubin \> 1.5x ULN wiht ratio of direct/indirect \>1. ALT or AST levels \> 5x ULN INR prolonged to \>1.5x ULN Exclusion criteria related to PegIFN and/or RBV restrictions.

Primary outcomes:
measure: Virological Response 4 Weeks After the End of Treatment With BI 201335 or Placebo
timeFrame: Week 28
measure: Sustained Virological Response 24 Weeks (SVR24) After Completion of All Therapy
timeFrame: Day 155 after the end of all treatment
Secondary outcomes:
measure: Virological Response at Week 2
timeFrame: Week 2
measure: Virological Response at Week 4
timeFrame: Week 4
measure: Early Virological Response (EVR)
timeFrame: Baseline and Week 12
measure: Extended Rapid Virological Response (eRVR)
timeFrame: Week 4 and Week 12
measure: Complete Early Virological Response (cEVR)
timeFrame: Week 12
measure: End of Treatment Response at Week 24
timeFrame: Week 24
measure: End of Treatment Response at End of All Therapy
timeFrame: Week 24 or Week 48
measure: Sustained Virological Response 12 Weeks (SVR12) After Completion of All Therapy
timeFrame: Week 36 or Week 60
measure: Time to Reach a Plasma HCV RNA Level Below the Lower Limit of Detection
timeFrame: On or after day 155 post end of all treatment
measure: Time to Loss of Virological Response
timeFrame: Week 24
measure: Virological Rebound
timeFrame: Week 24 or Week 48
measure: Breakthrough on BI 201335/Placebo (Rebound While All 3 Treatments Were Still Ongoing)
timeFrame: Up to Week 24
measure: Breakthrough on PegIFN/RBV (Rebound While Only PegIFN/RBV Treatment Alone Was Still Ongoing)
timeFrame: Week 24 through Week 48
measure: Relapse
timeFrame: post-End of treatment (i.e. post 48 weeks)
measure: Change From Baseline to Week 24 in Diastolic Blood Pressure and Systolic Blood Pressure
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Pulse Rate
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Weight of the Patients
timeFrame: Baseline and Week 24
measure: Global Assessment of Tolerability
timeFrame: Week 24
measure: Change From Baseline to Week 24 in Haemoglobin of the Patients
timeFrame: Baseline and Week 24
measure: Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Haemoglobin
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Absolute Neutrophils of the Patients
timeFrame: Baseline and Week 24
measure: Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Absolute Neutrophils
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in ALT/GPT,SGPT of the Patients
timeFrame: Baseline and Week 24
measure: Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter ALT/GPT,SGPT
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Total Bilirubin of the Patients
timeFrame: Baseline and Week 24
measure: Number of Patients [N(%)] With Transitions Relative to Reference Range for Laboratory Parameter Total Bilirubin
timeFrame: Baseline and Week 24
measure: Trough Concentration (Cpre,ss) of Faldaprevir at Steady State
timeFrame: Week 8, week 10, week 12, week 24
measure: Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1000 mg/Day RBV)
timeFrame: Week 8, week 10, week 12, week 24
measure: Trough Concentration (Cpre,ss) of Ribavirin at Steady State (Receiving 1200 mg/Day RBV)
timeFrame: Week 8, week 10, week 12, week 24
measure: Trough Concentration (Cpre,ss) of PegIFN at Steady State
timeFrame: Week 8, week 10, week 12, week 24
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: 1220.5.0001 Boehringer Ingelheim Investigational Site
state: California
city: San Francisco
country: United States
facility: 1220.5.0008 Boehringer Ingelheim Investigational Site
state: California
city: Chicago
country: United States
facility: 1220.5.0005 Boehringer Ingelheim Investigational Site
state: Illinois
city: Lutherville
country: United States
facility: 1220.5.0006 Boehringer Ingelheim Investigational Site
state: Maryland
city: New York
country: United States
facility: 1220.5.0002 Boehringer Ingelheim Investigational Site
state: New York
city: New York
country: United States
facility: 1220.5.0003 Boehringer Ingelheim Investigational Site
state: New York
city: Philadelphia
country: United States
facility: 1220.5.0007 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Germantown
country: United States
facility: 1220.5.0010 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: 1220.5.0009 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Austin
country: United States
facility: 1220.5.0004 Boehringer Ingelheim Investigational Site
state: Texas
city: Capital Federal
country: Argentina
facility: 1220.5.5401 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 1220.5.5403 Boehringer Ingelheim Investigational Site
city: Derqui, Pilar
country: Argentina
facility: 1220.5.5405 Boehringer Ingelheim Investigational Site
city: Rosario
country: Argentina
facility: 1220.5.5402 Boehringer Ingelheim Investigational Site
city: Rosario
country: Argentina
facility: 1220.5.5406 Boehringer Ingelheim Investigational Site
city: Camperdown
country: Australia
facility: 1220.5.6110 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Kogarah
country: Australia
facility: 1220.5.6109 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Randwick
country: Australia
facility: 1220.5.6105 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Westmead
country: Australia
facility: 1220.5.6101 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: 1220.5.6103 Boehringer Ingelheim Investigational Site
state: Queensland
city: Woolloongabba
country: Australia
facility: 1220.5.6104 Boehringer Ingelheim Investigational Site
state: Queensland
city: Clayton
country: Australia
facility: 1220.5.6102 Boehringer Ingelheim Investigational Site
state: Victoria
city: Fitzroy
country: Australia
facility: 1220.5.6107 Boehringer Ingelheim Investigational Site
state: Victoria
city: Parkville
country: Australia
facility: 1220.5.6108 Boehringer Ingelheim Investigational Site
state: Victoria
city: Linz
country: Austria
facility: 1220.5.4303 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1220.5.4301 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1220.5.4302 Boehringer Ingelheim Investigational Site
city: Edmonton
country: Canada
facility: 1220.5.1003 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1220.5.1007 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: 1220.5.1006 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: 1220.5.1001 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1220.5.1002 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1220.5.1004 Boehringer Ingelheim Investigational Site
state: Quebec
city: Melnik
country: Czech Republic
facility: 1220.5.4202 Boehringer Ingelheim Investigational Site
city: Opava
country: Czech Republic
facility: 1220.5.4203 Boehringer Ingelheim Investigational Site
city: Clichy
country: France
facility: 1220.5.3301A Boehringer Ingelheim Investigational Site
city: Creteil
country: France
facility: 1220.5.3307A Boehringer Ingelheim Investigational Site
city: Lyon
country: France
facility: 1220.5.3309A Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 1220.5.3304A Boehringer Ingelheim Investigational Site
city: Montpellier
country: France
facility: 1220.5.3306A Boehringer Ingelheim Investigational Site
city: Paris Cedex 20
country: France
facility: 1220.5.3308A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1220.5.3302A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1220.5.3303A Boehringer Ingelheim Investigational Site
city: Vandoeuvre Cedex
country: France
facility: 1220.5.3305A Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1220.5.4902 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1220.5.4903 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1220.5.4917 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 1220.5.4914 Boehringer Ingelheim Investigational Site
city: Bonn
country: Germany
facility: 1220.5.4913 Boehringer Ingelheim Investigational Site
city: Dortmund
country: Germany
facility: 1220.5.4915 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1220.5.4905 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1220.5.4912 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 1220.5.4906 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1220.5.4908 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1220.5.4904 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 1220.5.4910 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1220.5.4909 Boehringer Ingelheim Investigational Site
city: Tübingen
country: Germany
facility: 1220.5.4907 Boehringer Ingelheim Investigational Site
city: Busan
country: Korea, Republic of
facility: 1220.5.8210 Boehringer Ingelheim Investigational Site
city: Daegu
country: Korea, Republic of
facility: 1220.5.8205 Boehringer Ingelheim Investigational Site
city: Pusan
country: Korea, Republic of
facility: 1220.5.8201 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.5.8202 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.5.8206 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.5.8207 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.5.8208 Boehringer Ingelheim Investigational Site
city: Seoungnam
country: Korea, Republic of
facility: 1220.5.8204 Boehringer Ingelheim Investigational Site
city: Sungnam
country: Korea, Republic of
facility: 1220.5.8203 Boehringer Ingelheim Investigational Site
city: Suwon
country: Korea, Republic of
facility: 1220.5.8209 Boehringer Ingelheim Investigational Site
city: Yangsan
country: Korea, Republic of
facility: 1220.5.8211 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1220.5.3101 Boehringer Ingelheim Investigational Site
city: Leiden
country: Netherlands
facility: 1220.5.3102 Boehringer Ingelheim Investigational Site
city: Coimbra
country: Portugal
facility: 1220.5.3501 Boehringer Ingelheim Investigational Site
city: Coimbra
country: Portugal
facility: 1220.5.3504 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1220.5.3502 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1220.5.3503 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1220.5.3506 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1220.5.3507 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.5.4001 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.5.4002 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.5.4003 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.5.4004 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.5.3402 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.5.3405 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1220.5.3401 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1220.5.3403 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1220.5.3404 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1220.5.3406 Boehringer Ingelheim Investigational Site
city: Bern
country: Switzerland
facility: 1220.5.4104 Boehringer Ingelheim Investigational Site
city: La Chaux-de-Fonds
country: Switzerland
facility: 1220.5.4102 Boehringer Ingelheim Investigational Site
city: Lugano
country: Switzerland
facility: 1220.5.4103 Boehringer Ingelheim Investigational Site
city: Zürich
country: Switzerland
facility: 1220.5.4101 Boehringer Ingelheim Investigational Site
city: Zürich
country: Switzerland
facility: 1220.5.4106 Boehringer Ingelheim Investigational Site
city: Bristol
country: United Kingdom
facility: 1220.5.4405 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.5.4401 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.5.4402 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.5.4406 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.5.4409 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.5.4410 Boehringer Ingelheim Investigational Site
city: Nottingham
country: United Kingdom
facility: 1220.5.4408 Boehringer Ingelheim Investigational Site
city: Southampton
country: United Kingdom
facility: 1220.5.4403 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: