A Rollover Study of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-experienced Genotype 1 Hepatitis C Infected Patients

A Phase III, Open-label Study of Once Daily BI 201335 240 mg for 24 Weeks in Combination With Pegylated interferon-a (PegIFN) and Ribavirin (RBV) in Patients With Genotype 1 Chronic Hepatitis C Infection Who Failed a Prior PegIFN / RBV Treatment

The objective of this trial is to collect evidence for the safety and efficacy of 24 weeks of treatment with BI 201335 240 mg in combination with 24 or 48 weeks of Pegylated Interferon (PegIFN) and ribavirin (RBV) in treatment experienced patients who have been withdrawn from PegIFN and RBV treatment due to lack of efficacy in the 1220.7, 1220.30 and 1220.47 trials.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: PegIFN/RBV; Drug: BI 201335

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria
    • 1220.48.4301 Boehringer Ingelheim Investigational Site
  • Wien, Austria
    • 1220.48.4302 Boehringer Ingelheim Investigational Site
• Belgium
  • Bruxelles, Belgium
    • 1220.48.3201 Boehringer Ingelheim Investigational Site
  • Edegem, Belgium
    • 1220.48.3204 Boehringer Ingelheim Investigational Site
  • Liège, Belgium
    • 1220.48.3203 Boehringer Ingelheim Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • 1220.48.1012 Boehringer Ingelheim Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • 1220.48.1003 Boehringer Ingelheim Investigational Site
    • Vancouver, British Columbia, Canada
      • 1220.48.1016 Boehringer Ingelheim Investigational Site
    • Victoria, British Columbia, Canada
      • 1220.48.1007 Boehringer Ingelheim Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • 1220.48.1009 Boehringer Ingelheim Investigational Site
  • Ontario
    • Toronto, Ontario, Canada
      • 1220.48.1005 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1220.48.1006 Boehringer Ingelheim Investigational Site
• France
  • Clichy Cedex, France
    • 1220.48.3301 Boehringer Ingelheim Investigational Site
  • Lille Cedex, France
    • 1220.48.3311 Boehringer Ingelheim Investigational Site
  • Marseille Cedex 08, France
    • 1220.48.3303 Boehringer Ingelheim Investigational Site
  • Montpellier Cedex 5, France
    • 1220.48.3304 Boehringer Ingelheim Investigational Site
  • Nice Cedex 3, France
    • 1220.48.3305 Boehringer Ingelheim Investigational Site
  • Pessac Cedex, France
    • 1220.48.3316 Boehringer Ingelheim Investigational Site
  • Saint Laurent du Var, France
    • 1220.48.3312 Boehringer Ingelheim Investigational Site
• Germany
  • Berlin, Germany
    • 1220.48.4902 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1220.48.4904 Boehringer Ingelheim Investigational Site
  • Dortmund, Germany
    • 1220.48.4913 Boehringer Ingelheim Investigational Site
  • Düsseldorf, Germany
    • 1220.48.4906 Boehringer Ingelheim Investigational Site
  • Frankfurt am Main, Germany
    • 1220.48.4901 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1220.48.4908 Boehringer Ingelheim Investigational Site
  • Kiel, Germany
    • 1220.48.4914 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1220.48.4911 Boehringer Ingelheim Investigational Site
  • München, Germany
    • 1220.48.4905 Boehringer Ingelheim Investigational Site
• Japan
  • Chiba, Chiba, Japan
    • 1220.48.8106 Boehringer Ingelheim Investigational Site
  • Kita-gun, Kagawa, Japan
    • 1220.48.8117 Boehringer Ingelheim Investigational Site
  • Kurashiki, Okayama, Japan
    • 1220.48.8116 Boehringer Ingelheim Investigational Site
  • Kurume, Fukuoka, Japan
    • 1220.48.8118 Boehringer Ingelheim Investigational Site
  • Nagoya, Aichi, Japan
    • 1220.48.8113 Boehringer Ingelheim Investigational Site
  • Nishinomiya, Hyogo, Japan
    • 1220.48.8114 Boehringer Ingelheim Investigational Site
  • Omura, Nagasaki, Japan
    • 1220.48.8119 Boehringer Ingelheim Investigational Site
  • Osaka, Osaka, Japan
    • 1220.48.8121 Boehringer Ingelheim Investigational Site
• Korea, Republic of
  • Pusan, Korea, Republic of
    • 1220.48.8204 Boehringer Ingelheim Investigational Site
  • Pusan, Korea, Republic of
    • 1220.48.8205 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1220.48.8206 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1220.48.8207 Boehringer Ingelheim Investigational Site
  • Yangsan, Korea, Republic of
    • 1220.48.8201 Boehringer Ingelheim Investigational Site
• Portugal
  • Aveiro, Portugal
    • 1220.48.3503 Boehringer Ingelheim Investigational Site
  • Barreiro, Portugal
    • 1220.48.3509 Boehringer Ingelheim Investigational Site
  • Lisboa, Portugal
    • 1220.48.3501 Boehringer Ingelheim Investigational Site
  • Porto, Portugal
    • 1220.48.3502 Boehringer Ingelheim Investigational Site
• Romania
  • Bucharest, Romania
    • 1220.48.4002 Boehringer Ingelheim Investigational Site
• Russian Federation
  • Moscow, Russian Federation
    • 1220.48.7001 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 1220.48.7004 Boehringer Ingelheim Investigational Site
• Spain
  • A Coruña, Spain
    • 1220.48.3406 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 1220.48.3402 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 1220.48.3404 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 1220.48.3411 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 1220.48.3412 Boehringer Ingelheim Investigational Site
  • Madrid, Spain
    • 1220.48.3405 Boehringer Ingelheim Investigational Site
  • Madrid, Spain
    • 1220.48.3409 Boehringer Ingelheim Investigational Site
  • Majadahonda-Madrid, Spain
    • 1220.48.3410 Boehringer Ingelheim Investigational Site
  • Sevilla, Spain
    • 1220.48.3403 Boehringer Ingelheim Investigational Site
  • Valencia, Spain
    • 1220.48.3401 Boehringer Ingelheim Investigational Site
• Switzerland
  • Bern, Switzerland
    • 1220.48.4106 Boehringer Ingelheim Investigational Site
• Taiwan
  • Taichung, Taiwan
    • 1220.48.8802 China Medical University Hospital
• United Kingdom
  • Bristol, United Kingdom
    • 1220.48.4405 Boehringer Ingelheim Investigational Site
  • London, United Kingdom
    • 1220.48.4409 Boehringer Ingelheim Investigational Site
  • Manchester, United Kingdom
    • 1220.48.4401 Boehringer Ingelheim Investigational Site
  • Nottingham, United Kingdom
    • 1220.48.4408 Boehringer Ingelheim Investigational Site
  • Oxford, United Kingdom
    • 1220.48.4407 Boehringer Ingelheim Investigational Site
  • Southampton, United Kingdom
    • 1220.48.4403 Boehringer Ingelheim Investigational Site
  • Tooting, London, United Kingdom
    • 1220.48.4404 Boehringer Ingelheim Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • 1220.48.0004 Boehringer Ingelheim Investigational Site
  • Arkansas
    • North Little Rock, Arkansas, United States
      • 1220.48.0091 Boehringer Ingelheim Investigational Site
  • California
    • Los Angeles, California, United States
      • 1220.48.0011 Boehringer Ingelheim Investigational Site
    • Oceanside, California, United States
      • 1220.48.0018 Boehringer Ingelheim Investigational Site
  • Florida
    • Fort Lauderdale, Florida, United States
      • 1220.48.0078 Boehringer Ingelheim Investigational Site
    • Palm Harbor, Florida, United States
      • 1220.48.0095 Boehringer Ingelheim Investigational Site
  • Georgia
    • Columbus, Georgia, United States
      • 1220.48.0039 Boehringer Ingelheim Investigational Site
  • Illinois
    • Chicago, Illinois, United States
      • 1220.48.0013 Boehringer Ingelheim Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States
      • 1220.48.0087 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • Framingham, Massachusetts, United States
      • 1220.48.0027 Boehringer Ingelheim Investigational Site
    • Springfield, Massachusetts, United States
      • 1220.48.0065 Boehringer Ingelheim Investigational Site
  • Mississippi
    • Tupelo, Mississippi, United States
      • 1220.48.0023 Boehringer Ingelheim Investigational Site
  • New Jersey
    • Neptune, New Jersey, United States
      • 1220.48.0066 Boehringer Ingelheim Investigational Site
  • New York
    • New York, New York, United States
      • 1220.48.0012 Boehringer Ingelheim Investigational Site
  • Oregon
    • Portland, Oregon, United States
      • 1220.48.0058 Boehringer Ingelheim Investigational Site
  • Texas
    • Arlington, Texas, United States
      • 1220.48.0063 Boehringer Ingelheim Investigational Site
    • Austin, Texas, United States
      • 1220.48.0029 Boehringer Ingelheim Investigational Site
    • Dallas, Texas, United States
      • 1220.48.0017 Boehringer Ingelheim Investigational Site
    • Dallas, Texas, United States
      • 1220.48.0071 Boehringer Ingelheim Investigational Site
    • Forth Worth, Texas, United States
      • 1220.48.0081 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:

Chronic hepatitis C infection of GT-1 in patients who failed prior treatment with PegIFN and RBV in the 1220.7, 1220.30 and 1220.47 trials of the BI 201335 Phase III program.

1. Patients from trials 1220.7, 1220.30 and 1220.47 of BI 201335 who have failed treatment with PegIFN/RBV in the placebo groups due to protocol-defined criteria of treatment failure (i.e. either non-response on treatment or relapse after end of treatment [EOT]).
2. Patients must have received at least 4 weeks of assigned trial medication and been compliant with all study procedures.

3. Female patients:

   • with documented hysterectomy,
   • who have had both ovaries removed,
   • with documented tubal ligation,
   • who are post-menopausal with last menstrual period at least 12 months prior to screening, or
   • of childbearing potential with a negative serum pregnancy test at screening and Day 1, that, if sexually active, agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of RBV in addition to the consistent and correct use of a condom. Patients must agree not to breast-feed at any time from the date of screening until 7 months after the last dose of RBV.

   Medically accepted methods of contraception for females in this trial are ethinyl estradiol-containing contraceptives, diaphragm with spermicide substance, intra-uterine device and cervical cap.

   or

   Male patients:

   • who are documented to be sterile, or
   • who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin. It is in the responsibility of the male patient to ensure that his partner(s) is not pregnant prior to screening into the study or becomes pregnant during the treatment and the observation phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor).
4. Signed informed consent form prior to trial participation.

Exclusion criteria:

1. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. Incidental steatosis diagnosed by biopsy is not an exclusion criteria.
2. HIV co-infection
3. Hepatitis B virus (HBV) infection based on presence of HBs-Ag
4. Active malignancy, or history of malignancy within the last 5 years prior to screening (with an exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix)
5. Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months
6. A condition that is defined as one which in the opinion of investigator may put the patient at risk because of participation in this study, may influence the results of this study, or limit the patients ability to participate in this study
7. Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study.
8. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to screening. Patients being treated with oral antivirals such as acyclovir, famciclovir or valacyclovir for recurrent herpes simplex infection; or with oseltamivir or zanamivir for influenza A infection, may be screened.
9. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to enrolment and throughout the treatment phase of this trial.
10. Known hypersensitivity to any ingredient of the study drugs.
11. Alpha fetoprotein value > 100 ng/mL at screening; if > 20 ng/mL and = 100 ng/mL, patients may be included if there is no evidence of liver cancer in an appropriate imaging study (e.g., ultrasound, CT scan, or MRI) within last 6 months prior to randomization (Visit 2).

Other exclusion criteria related to pegylated interferon and/or ribavirin restrictions are not listed here.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI 201335 for 24 weeks; BI 201335 once daily dose for 24 weeks in combination with PegIFN/RBV for 24 or 48 weeks	Drug: PegIFN/RBV; PegIFN/RBV for 48 weeks; Drug: BI 201335; BI 201335 for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL	The primary endpoint was SVR12, defined as a plasma Hepatitis C virus (HCV) Ribonucleic acid (RNA) level <25 IU/mL (undetected) 12 weeks after the originally planned treatment duration.	12 weeks post treatment, up to 60 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24)	Sustained virologic response 24 weeks, defined as a plasma HCV RNA level < 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration.	24 weeks post treatment, up to 72 weeks
Early Treatment Success (ETS)	ETS, defined as a plasma HCV RNA level <25 IU/mL (detected or undetected) at week 4 and HCV RNA <25 IU/mL (undetected) at week 8.	week 4 and week 8
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT)	This will be presented as the number of patients in/not in normal range from baseline EoT. SVR12 is sustained virological response 12 weeks post-treatment.	Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment.	This will be presented as the number of patients in/not in normal range from baseline to 12 weeks post treatment. SVR12 is sustained virological response 12 weeks post-treatment.	48 weeks for relapsers with ETS; 60 weeks for non-relapsers and relapsers without ETS
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT)	This will be presented as the number of patients in/not in normal range from baseline to EoT. SVR12 is sustained virological response 12 weeks post-treatment.	Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers.
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment.	This will be presented as the number of patients in/not in normal range from baseline to 12 weeks post treatment. SVR12 is sustained virological response 12 weeks post-treatment.	Week 48 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
Occurrence of Adverse Events (Overall and by DAIDS Grade)	This outcome measure will be presented as the percentage of subjects with any adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator. The intensity of all AEs was evaluated according to the DAIDS (Division of Acquired Immunodeficiency Syndrome) grading scale with AEs of mild, moderate, or severe intensity receiving Grades 1, 2, or 3, respectively. Adverse events judged potentially life threatening received a Grade 4 assessment.	from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Occurrence of Adverse Events Leading to Treatment Discontinuation	This outcome measure will be presented as the percentage of subjects with adverse events leading to discontinuation of Faldaprevir and all study medication. Percentages are calculated using total number of subjects per treatment cohort as the denominator.	from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Occurrence of Serious Adverse Events (SAEs)	This outcome measure will be presented as the percentage of subjects with any serious adverse event (SAE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.	from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Occurrence of Drug-related AEs as Assessed by the Investigator	This outcome measure will be presented as the percentage of subjects with any drug-related AEs as assessed by the investigator. Percentages are calculated using total number of subjects per treatment cohort as the denominator.	from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Laboratory Test Abnormalities by DAIDS Grades	This Outcome measure will be presented as summary of the percentage of patients with worst on-treatment Division of Acquired Immunodeficiency Syndrome (DAIDS) grade laboratory abnormalities for selected analytes (Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total) with particular relevance to patients with HCV.	baseline (day 1, after first dose of randomised treatment) up to 7 days after the last intake of study
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin]	This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total. In this outcome measure Haemoglobin is presented.	baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Changes From Baseline in Laboratory Test Values Over Time [ALT]	This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total. In this outcome measure ALT is presented.	baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Changes From Baseline in Laboratory Test Values Over Time [AST]	This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total. In this outcome measure AST is presented.	baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total]	This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total. In this outcome measure Bilirubin total is presented.	baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Foster GR, Ferenci P, Asselah T, Mantry P, Dufour JF, Bourliere M, Forton D, Maevskaya M, Wright D, Yoshida EM, Garcia-Samaniego J, Oliveira C, Wright M, Warner N, Sha N, Quinson AM, Stern JO. Open-label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1-infected patients who failed placebo plus peginterferon and ribavirin. J Viral Hepat. 2016 Mar;23(3):227-31. doi: 10.1111/jvh.12485. Epub 2015 Nov 17.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: April 5, 2011
• First Submitted That Met QC Criteria: April 5, 2011
• First Posted (Estimate): April 6, 2011

Study Record Updates

• Last Update Posted (Estimate): June 30, 2016
• Last Update Submitted That Met QC Criteria: May 31, 2016
• Last Verified: May 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; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: 1220.48; 2011-000141-20 (EudraCT Number: EudraCT)