Efficacy and Safety of BI 201335 (Faldaprevir) in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-naïve Genotype 1 Hepatitis C Infected Patients (STARTverso 1)

Hepatitis C Clinical Trial

Official title:

A Phase III, Randomised, Double-blind and Placebo-controlled Study of Once Daily BI 201335 120 mg for 12 or 24 Weeks or BI 201335 240 mg for 12 Weeks in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-naïve Patients With Genotype 1 Chronic Hepatitis C Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01343888
• Other study ID #: 1220.30
• Secondary ID: 2010-021716-42
• Status: Completed
• Phase: Phase 3
• First received: April 20, 2011
• Last updated: August 18, 2015
• Start date: April 2011
• Est. completion date: March 2014

Study information

• Verified date: August 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 ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: 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 HealthSpain: Spanish Agency of MedicinesSwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this trial is to evaluate the efficacy and safety of two different treatment regimens with BI 201335, both in combination with PegIFN/RBV) as compared to standard of care (SOC) with PegIFN/RBV alone.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 656
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria:

1. Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detected HCV RNA at screening in addition to:

1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or,

2. liver biopsy consistent with chronic HCV infection.

2. HCV genotype 1 infection confirmed by genotypic testing at screening.

3. Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection.

4. HCV RNA = 1,000 IU/mL at screening

5. Documentation of a liver biopsy within 3 years or fibroscan within 6 months prior to randomization.

Note: If cirrhosis has been previously demonstrated on a biopsy, then biopsies obtained more than 3 years before randomization need not be repeated. Biopsies may be waived for patients who would be placed at risk from the procedure. Inability to do a liver biopsy in patients at risk for the procedure should not exclude such patients from a trial.

6. Age 18 to 70 years

7. Female patients:

1. with documented hysterectomy,

2. who have had both ovaries removed,

3. with documented tubal ligation,

4. who are post-menopausal with last menstrual period at least 12 months prior to screening, or

5. 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 ribavirin 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 ribavirin.

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

Male patients:

1. who are documented to be sterile, or

2. who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) 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 should 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).

8. Signed informed consent form prior to trial participation

Exclusion criteria:

1. HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening

2. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. Incidental steatosis diagnosed by biopsy is not an exclusion criterion.

3. HIV co-infection

4. Hepatitis B virus (HBV) infection based on presence of HBs-Ag

5. 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)

6. Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months

7. 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

8. Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study.

9. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to randomization. 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.

10. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to randomization and throughout the treatment phase of this trial.

11. Known hypersensitivity to any ingredient of the study drugs.

12. 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: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• PegIFN/RBV
PegIFN/RBV for 48 weeks
• BI 201335
BI 201335 once daily high dose
• BI 201335
BI 201335 once daily low dose
• Placebo

Locations

Country	Name	City	State
Austria	1220.30.4303 Boehringer Ingelheim Investigational Site	Linz
Austria	1220.30.4301 Boehringer Ingelheim Investigational Site	Wien
Austria	1220.30.4302 Boehringer Ingelheim Investigational Site	Wien
Austria	1220.30.4304 Boehringer Ingelheim Investigational Site	Wien
Belgium	1220.30.3201 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1220.30.3207 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1220.30.3204 Boehringer Ingelheim Investigational Site	Edegem
Belgium	1220.30.3205 Boehringer Ingelheim Investigational Site	Gent
Belgium	1220.30.3202 Boehringer Ingelheim Investigational Site	Leuven
Belgium	1220.30.3203 Boehringer Ingelheim Investigational Site	Liège
France	1220.30.3314 Boehringer Ingelheim Investigational Site	Clermont-Ferrand
France	1220.30.3301 Boehringer Ingelheim Investigational Site	Clichy
France	1220.30.3311 Boehringer Ingelheim Investigational Site	Lille
France	1220.30.3303 Boehringer Ingelheim Investigational Site	Marseille
France	1220.30.3304 Boehringer Ingelheim Investigational Site	Montpellier
France	1220.30.3305 Boehringer Ingelheim Investigational Site	Nice Cedex 3
France	1220.30.3302 Boehringer Ingelheim Investigational Site	Paris
France	1220.30.3309 Boehringer Ingelheim Investigational Site	Paris Cedex 20
France	1220.30.3316 Boehringer Ingelheim Investigational Site	Pessac Cedex
France	1220.30.3315 Boehringer Ingelheim Investigational Site	Rennes Cedex 09
France	1220.30.3312 Boehringer Ingelheim Investigational Site	Saint Laurent du Var
France	1220.30.3313 Boehringer Ingelheim Investigational Site	Toulouse
Germany	1220.30.4917 Boehringer Ingelheim Investigational Site	Aachen
Germany	1220.30.4902 Boehringer Ingelheim Investigational Site	Berlin
Germany	1220.30.4904 Boehringer Ingelheim Investigational Site	Berlin
Germany	1220.30.4916 Boehringer Ingelheim Investigational Site	Bonn
Germany	1220.30.4913 Boehringer Ingelheim Investigational Site	Dortmund
Germany	1220.30.4906 Boehringer Ingelheim Investigational Site	Düsseldorf
Germany	1220.30.4909 Boehringer Ingelheim Investigational Site	Düsseldorf
Germany	1220.30.4912 Boehringer Ingelheim Investigational Site	Erlangen
Germany	1220.30.4901 Boehringer Ingelheim Investigational Site	Frankfurt am Main
Germany	1220.30.4908 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1220.30.4907 Boehringer Ingelheim Investigational Site	Herne
Germany	1220.30.4914 Boehringer Ingelheim Investigational Site	Kiel
Germany	1220.30.4903 Boehringer Ingelheim Investigational Site	Leipzig
Germany	1220.30.4911 Boehringer Ingelheim Investigational Site	Mainz
Germany	1220.30.4905 Boehringer Ingelheim Investigational Site	München
Germany	1220.30.4915 Boehringer Ingelheim Investigational Site	Ulm
Japan	1220.30.8106 Boehringer Ingelheim Investigational Site	Chiba, Chiba
Japan	1220.30.8111 Boehringer Ingelheim Investigational Site	Gifu, Gifu
Japan	1220.30.8107 Boehringer Ingelheim Investigational Site	Itabashi-ku, Tokyo
Japan	1220.30.8112 Boehringer Ingelheim Investigational Site	Izunokuni, Shizuoka
Japan	1220.30.8108 Boehringer Ingelheim Investigational Site	Kamakura, Kanagawa
Japan	1220.30.8117 Boehringer Ingelheim Investigational Site	Kita-gun, Kagawa
Japan	1220.30.8109 Boehringer Ingelheim Investigational Site	Kofu, Yamanashi
Japan	1220.30.8116 Boehringer Ingelheim Investigational Site	Kurashiki, Okayama
Japan	1220.30.8118 Boehringer Ingelheim Investigational Site	Kurume, Fukuoka
Japan	1220.30.8110 Boehringer Ingelheim Investigational Site	Matsumoto, Nagano
Japan	1220.30.8113 Boehringer Ingelheim Investigational Site	Nagoya, Aichi
Japan	1220.30.8105 Boehringer Ingelheim Investigational Site	Namegata, Ibaraki
Japan	1220.30.8114 Boehringer Ingelheim Investigational Site	Nishinomiya, Hyogo
Japan	1220.30.8119 Boehringer Ingelheim Investigational Site	Omura, Nagasaki
Japan	1220.30.8122 Boehringer Ingelheim Investigational Site	Omuta, Fukuoka
Japan	1220.30.8121 Boehringer Ingelheim Investigational Site	Osaka, Osaka
Japan	1220.30.8101 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido
Japan	1220.30.8102 Boehringer Ingelheim Investigational Site	Sendai, Miyagi
Japan	1220.30.8115 Boehringer Ingelheim Investigational Site	Tanabe, Wakayama
Japan	1220.30.8104 Boehringer Ingelheim Investigational Site	Tsuchiura, Ibaraki
Portugal	1220.30.3503 Boehringer Ingelheim Investigational Site	Aveiro
Portugal	1220.30.3509 Boehringer Ingelheim Investigational Site	Barreiro
Portugal	1220.30.3506 Boehringer Ingelheim Investigational Site	Coimbra
Portugal	1220.30.3501 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	1220.30.3505 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	1220.30.3507 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	1220.30.3502 Boehringer Ingelheim Investigational Site	Porto
Portugal	1220.30.3504 Boehringer Ingelheim Investigational Site	Vila Real
Romania	1220.30.4001 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1220.30.4002 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1220.30.4003 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1220.30.4004 Boehringer Ingelheim Investigational Site	Bucharest
Russian Federation	1220.30.7002 Boehringer Ingelheim Investigational Site	Chelyabinsk
Russian Federation	1220.30.7001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1220.30.7004 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1220.30.7005 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1220.30.7006 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1220.30.7007 Boehringer Ingelheim Investigational Site	St. Petersburg
Spain	1220.30.3406 Boehringer Ingelheim Investigational Site	A Coruña
Spain	1220.30.3402 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1220.30.3404 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1220.30.3405 Boehringer Ingelheim Investigational Site	Madrid
Spain	1220.30.3408 Boehringer Ingelheim Investigational Site	Santander
Spain	1220.30.3403 Boehringer Ingelheim Investigational Site	Sevilla
Spain	1220.30.3401 Boehringer Ingelheim Investigational Site	Valencia
Spain	1220.30.3407 Boehringer Ingelheim Investigational Site	Vigo (Pontevedra)
Switzerland	1220.30.4106 Boehringer Ingelheim Investigational Site	Bern
Switzerland	1220.30.4103 Boehringer Ingelheim Investigational Site	La Chaux-de-Fonds
Switzerland	1220.30.4107 Boehringer Ingelheim Investigational Site	Lugano
Switzerland	1220.30.4108 Boehringer Ingelheim Investigational Site	St. Gallen
Switzerland	1220.30.4101 Boehringer Ingelheim Investigational Site	Zürich
United Kingdom	1220.30.4405 Boehringer Ingelheim Investigational Site	Bristol
United Kingdom	1220.30.4404 Boehringer Ingelheim Investigational Site	London
United Kingdom	1220.30.4409 Boehringer Ingelheim Investigational Site	London
United Kingdom	1220.30.4410 Boehringer Ingelheim Investigational Site	London
United Kingdom	1220.30.4401 Boehringer Ingelheim Investigational Site	Manchester
United Kingdom	1220.30.4408 Boehringer Ingelheim Investigational Site	Nottingham
United Kingdom	1220.30.4407 Boehringer Ingelheim Investigational Site	Oxford
United Kingdom	1220.30.4403 Boehringer Ingelheim Investigational Site	Southampton
United Kingdom	1220.30.4406 Boehringer Ingelheim Investigational Site	Whitechapel, London

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Japan,  Portugal,  Romania,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained Virological Response 12 Weeks Post-treatment (SVR12)	Sustained Virological Response 12 weeks post-treatment (SVR12), defined as 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 24 Weeks Post-treatment (SVR24)	Sustained Virological Response 24 weeks post-treatment (SVR24), defined as 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)	Early treatment success (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) When SVR12=YES	This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO	This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES	This will be presented as the number of patients. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO	This will be presented as the number of patients. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES	This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO	This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES	This will be presented as the number of patients. BL = Baseline	12 weeks post treatment, up to 60 weeks	No
Secondary	Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO	This will be presented as the number of patients. BL = Baseline	12 weeks post treatment, up to 60 weeks	No

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