Clinical trial NCT01330316: A Rollover Study of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-experienced Genotype 1 Hepatitis C Infected Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-04-06
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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24 or 48 weeks of Pegylated Interferon (PegIFN) and ribavirin (RBV) in treatment experienced patients who have been withdrawn from PegIFN and RBV treatment due to lack of efficacy in the 1220.7, 1220.30 and 1220.47 trials.


Eligibility criteria: 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.

Primary outcomes:
measure: Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL
timeFrame: 12 weeks post treatment, up to 60 weeks
Secondary outcomes:
measure: Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24)
timeFrame: 24 weeks post treatment, up to 72 weeks
measure: Early Treatment Success (ETS)
timeFrame: week 4 and week 8
measure: Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT)
timeFrame: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
measure: Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment.
timeFrame: 48 weeks for relapsers with ETS; 60 weeks for non-relapsers and relapsers without ETS
measure: Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT)
timeFrame: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers.
measure: Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment.
timeFrame: Week 48 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
measure: Occurrence of Adverse Events (Overall and by DAIDS Grade)
timeFrame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
measure: Occurrence of Adverse Events Leading to Treatment Discontinuation
timeFrame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
measure: Occurrence of Serious Adverse Events (SAEs)
timeFrame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
measure: Occurrence of Drug-related AEs as Assessed by the Investigator
timeFrame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
measure: Laboratory Test Abnormalities by DAIDS Grades
timeFrame: baseline (day 1, after first dose of randomised treatment) up to 7 days after the last intake of study
measure: Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin]
timeFrame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
measure: Changes From Baseline in Laboratory Test Values Over Time [ALT]
timeFrame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
measure: Changes From Baseline in Laboratory Test Values Over Time [AST]
timeFrame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
measure: Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total]
timeFrame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: 1220.48.0004 Boehringer Ingelheim Investigational Site
state: Alabama
city: North Little Rock
country: United States
facility: 1220.48.0091 Boehringer Ingelheim Investigational Site
state: Arkansas
city: Los Angeles
country: United States
facility: 1220.48.0011 Boehringer Ingelheim Investigational Site
state: California
city: Oceanside
country: United States
facility: 1220.48.0018 Boehringer Ingelheim Investigational Site
state: California
city: Fort Lauderdale
country: United States
facility: 1220.48.0078 Boehringer Ingelheim Investigational Site
state: Florida
city: Palm Harbor
country: United States
facility: 1220.48.0095 Boehringer Ingelheim Investigational Site
state: Florida
city: Columbus
country: United States
facility: 1220.48.0039 Boehringer Ingelheim Investigational Site
state: Georgia
city: Chicago
country: United States
facility: 1220.48.0013 Boehringer Ingelheim Investigational Site
state: Illinois
city: Baton Rouge
country: United States
facility: 1220.48.0087 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Framingham
country: United States
facility: 1220.48.0027 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: 1220.48.0065 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Tupelo
country: United States
facility: 1220.48.0023 Boehringer Ingelheim Investigational Site
state: Mississippi
city: Neptune
country: United States
facility: 1220.48.0066 Boehringer Ingelheim Investigational Site
state: New Jersey
city: New York
country: United States
facility: 1220.48.0012 Boehringer Ingelheim Investigational Site
state: New York
city: Portland
country: United States
facility: 1220.48.0058 Boehringer Ingelheim Investigational Site
state: Oregon
city: Arlington
country: United States
facility: 1220.48.0063 Boehringer Ingelheim Investigational Site
state: Texas
city: Austin
country: United States
facility: 1220.48.0029 Boehringer Ingelheim Investigational Site
state: Texas
city: Dallas
country: United States
facility: 1220.48.0017 Boehringer Ingelheim Investigational Site
state: Texas
city: Dallas
country: United States
facility: 1220.48.0071 Boehringer Ingelheim Investigational Site
state: Texas
city: Forth Worth
country: United States
facility: 1220.48.0081 Boehringer Ingelheim Investigational Site
state: Texas
city: Wien
country: Austria
facility: 1220.48.4301 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1220.48.4302 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1220.48.3201 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1220.48.3204 Boehringer Ingelheim Investigational Site
city: Liège
country: Belgium
facility: 1220.48.3203 Boehringer Ingelheim Investigational Site
city: Edmonton
country: Canada
facility: 1220.48.1012 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1220.48.1003 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: 1220.48.1016 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Victoria
country: Canada
facility: 1220.48.1007 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: 1220.48.1009 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Toronto
country: Canada
facility: 1220.48.1005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1220.48.1006 Boehringer Ingelheim Investigational Site
state: Ontario
city: Clichy Cedex
country: France
facility: 1220.48.3301 Boehringer Ingelheim Investigational Site
city: Lille Cedex
country: France
facility: 1220.48.3311 Boehringer Ingelheim Investigational Site
city: Marseille Cedex 08
country: France
facility: 1220.48.3303 Boehringer Ingelheim Investigational Site
city: Montpellier Cedex 5
country: France
facility: 1220.48.3304 Boehringer Ingelheim Investigational Site
city: Nice Cedex 3
country: France
facility: 1220.48.3305 Boehringer Ingelheim Investigational Site
city: Pessac Cedex
country: France
facility: 1220.48.3316 Boehringer Ingelheim Investigational Site
city: Saint Laurent du Var
country: France
facility: 1220.48.3312 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1220.48.4902 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1220.48.4904 Boehringer Ingelheim Investigational Site
city: Dortmund
country: Germany
facility: 1220.48.4913 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1220.48.4906 Boehringer Ingelheim Investigational Site
city: Frankfurt am Main
country: Germany
facility: 1220.48.4901 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1220.48.4908 Boehringer Ingelheim Investigational Site
city: Kiel
country: Germany
facility: 1220.48.4914 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1220.48.4911 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1220.48.4905 Boehringer Ingelheim Investigational Site
city: Chiba, Chiba
country: Japan
facility: 1220.48.8106 Boehringer Ingelheim Investigational Site
city: Kita-gun, Kagawa
country: Japan
facility: 1220.48.8117 Boehringer Ingelheim Investigational Site
city: Kurashiki, Okayama
country: Japan
facility: 1220.48.8116 Boehringer Ingelheim Investigational Site
city: Kurume, Fukuoka
country: Japan
facility: 1220.48.8118 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1220.48.8113 Boehringer Ingelheim Investigational Site
city: Nishinomiya, Hyogo
country: Japan
facility: 1220.48.8114 Boehringer Ingelheim Investigational Site
city: Omura, Nagasaki
country: Japan
facility: 1220.48.8119 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1220.48.8121 Boehringer Ingelheim Investigational Site
city: Pusan
country: Korea, Republic of
facility: 1220.48.8204 Boehringer Ingelheim Investigational Site
city: Pusan
country: Korea, Republic of
facility: 1220.48.8205 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.48.8206 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1220.48.8207 Boehringer Ingelheim Investigational Site
city: Yangsan
country: Korea, Republic of
facility: 1220.48.8201 Boehringer Ingelheim Investigational Site
city: Aveiro
country: Portugal
facility: 1220.48.3503 Boehringer Ingelheim Investigational Site
city: Barreiro
country: Portugal
facility: 1220.48.3509 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1220.48.3501 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1220.48.3502 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.48.4002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1220.48.7001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1220.48.7004 Boehringer Ingelheim Investigational Site
city: A Coruña
country: Spain
facility: 1220.48.3406 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.48.3402 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.48.3404 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.48.3411 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.48.3412 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1220.48.3405 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1220.48.3409 Boehringer Ingelheim Investigational Site
city: Majadahonda-Madrid
country: Spain
facility: 1220.48.3410 Boehringer Ingelheim Investigational Site
city: Sevilla
country: Spain
facility: 1220.48.3403 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 1220.48.3401 Boehringer Ingelheim Investigational Site
city: Bern
country: Switzerland
facility: 1220.48.4106 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1220.48.8802 China Medical University Hospital
city: Bristol
country: United Kingdom
facility: 1220.48.4405 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.48.4409 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 1220.48.4401 Boehringer Ingelheim Investigational Site
city: Nottingham
country: United Kingdom
facility: 1220.48.4408 Boehringer Ingelheim Investigational Site
city: Oxford
country: United Kingdom
facility: 1220.48.4407 Boehringer Ingelheim Investigational Site
city: Southampton
country: United Kingdom
facility: 1220.48.4403 Boehringer Ingelheim Investigational Site
city: Tooting, London
country: United Kingdom
facility: 1220.48.4404 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.