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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01330316
• Other study ID #: 1220.48
• Secondary ID: 2011-000141-20
• Status: Completed
• Phase: Phase 3
• First received: April 5, 2011
• Last updated: July 3, 2015
• Start date: July 2011
• Est. completion date: June 2014

Study information

• Verified date: July 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Medicines and Medical Devices AgencyBelgium: Federal Agency for Medicinal and Health ProductsCanada: Health CanadaFrance: Agence Nationale sécurité médicament et des produits santéGermany: Federal Institute for Drugs and Medical DevicesJapan: Ministry of Health, Labor and WelfarePortugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencyRussia: Pharmacological Committee, Ministry of HealthSouth Korea: Ministry of Food and Drug Safety (MFDS)Spain: Spanish Agency of MedicinesSwitzerland: SwissmedicTaiwan : Food and Drug AdministrationUnited Kingdom: Research Ethics CommitteeUnited States: Food and Drug Administration
• Study type: Interventional

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24 or 48 weeks of Pegylated Interferon (PegIFN) and ribavirin (RBV) in treatment experienced patients who have been withdrawn from PegIFN and RBV treatment due to lack of efficacy in the 1220.7, 1220.30 and 1220.47 trials.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• BI 201335
BI 201335 for 24 weeks
• PegIFN/RBV
PegIFN/RBV for 48 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Germany,  Japan,  Korea, Republic of,  Portugal,  Romania,  Russian Federation,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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.	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No

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