Clinical trial NCT01343888: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-04-28
Enrollment: 656
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Sustained Virological Response 12 Weeks Post-treatment (SVR12)
timeFrame: 12 weeks post treatment, up to 60 weeks
Secondary outcomes:
measure: Sustained Virological Response 24 Weeks Post-treatment (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) When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES
timeFrame: 12 weeks post treatment, up to 60 weeks
measure: Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO
timeFrame: 12 weeks post treatment, up to 60 weeks
Other outcomes:
Locations:
city: Linz
country: Austria
facility: 1220.30.4303 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1220.30.4301 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1220.30.4302 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1220.30.4304 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1220.30.3201 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1220.30.3207 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1220.30.3204 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1220.30.3205 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1220.30.3202 Boehringer Ingelheim Investigational Site
city: Liège
country: Belgium
facility: 1220.30.3203 Boehringer Ingelheim Investigational Site
city: Clermont-Ferrand
country: France
facility: 1220.30.3314 Boehringer Ingelheim Investigational Site
city: Clichy
country: France
facility: 1220.30.3301 Boehringer Ingelheim Investigational Site
city: Lille
country: France
facility: 1220.30.3311 Boehringer Ingelheim Investigational Site
city: Marseille
country: France
facility: 1220.30.3303 Boehringer Ingelheim Investigational Site
city: Montpellier
country: France
facility: 1220.30.3304 Boehringer Ingelheim Investigational Site
city: Nice Cedex 3
country: France
facility: 1220.30.3305 Boehringer Ingelheim Investigational Site
city: Paris Cedex 20
country: France
facility: 1220.30.3309 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1220.30.3302 Boehringer Ingelheim Investigational Site
city: Pessac Cedex
country: France
facility: 1220.30.3316 Boehringer Ingelheim Investigational Site
city: Rennes Cedex 09
country: France
facility: 1220.30.3315 Boehringer Ingelheim Investigational Site
city: Saint Laurent du Var
country: France
facility: 1220.30.3312 Boehringer Ingelheim Investigational Site
city: Toulouse
country: France
facility: 1220.30.3313 Boehringer Ingelheim Investigational Site
city: Aachen
country: Germany
facility: 1220.30.4917 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1220.30.4902 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1220.30.4904 Boehringer Ingelheim Investigational Site
city: Bonn
country: Germany
facility: 1220.30.4916 Boehringer Ingelheim Investigational Site
city: Dortmund
country: Germany
facility: 1220.30.4913 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1220.30.4906 Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: 1220.30.4909 Boehringer Ingelheim Investigational Site
city: Erlangen
country: Germany
facility: 1220.30.4912 Boehringer Ingelheim Investigational Site
city: Frankfurt am Main
country: Germany
facility: 1220.30.4901 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1220.30.4908 Boehringer Ingelheim Investigational Site
city: Herne
country: Germany
facility: 1220.30.4907 Boehringer Ingelheim Investigational Site
city: Kiel
country: Germany
facility: 1220.30.4914 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 1220.30.4903 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1220.30.4911 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1220.30.4905 Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: 1220.30.4915 Boehringer Ingelheim Investigational Site
city: Chiba, Chiba
country: Japan
facility: 1220.30.8106 Boehringer Ingelheim Investigational Site
city: Gifu, Gifu
country: Japan
facility: 1220.30.8111 Boehringer Ingelheim Investigational Site
city: Itabashi-ku, Tokyo
country: Japan
facility: 1220.30.8107 Boehringer Ingelheim Investigational Site
city: Izunokuni, Shizuoka
country: Japan
facility: 1220.30.8112 Boehringer Ingelheim Investigational Site
city: Kamakura, Kanagawa
country: Japan
facility: 1220.30.8108 Boehringer Ingelheim Investigational Site
city: Kita-gun, Kagawa
country: Japan
facility: 1220.30.8117 Boehringer Ingelheim Investigational Site
city: Kofu, Yamanashi
country: Japan
facility: 1220.30.8109 Boehringer Ingelheim Investigational Site
city: Kurashiki, Okayama
country: Japan
facility: 1220.30.8116 Boehringer Ingelheim Investigational Site
city: Kurume, Fukuoka
country: Japan
facility: 1220.30.8118 Boehringer Ingelheim Investigational Site
city: Matsumoto, Nagano
country: Japan
facility: 1220.30.8110 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1220.30.8113 Boehringer Ingelheim Investigational Site
city: Namegata, Ibaraki
country: Japan
facility: 1220.30.8105 Boehringer Ingelheim Investigational Site
city: Nishinomiya, Hyogo
country: Japan
facility: 1220.30.8114 Boehringer Ingelheim Investigational Site
city: Omura, Nagasaki
country: Japan
facility: 1220.30.8119 Boehringer Ingelheim Investigational Site
city: Omuta, Fukuoka
country: Japan
facility: 1220.30.8122 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1220.30.8121 Boehringer Ingelheim Investigational Site
city: Sapporo, Hokkaido
country: Japan
facility: 1220.30.8101 Boehringer Ingelheim Investigational Site
city: Sendai, Miyagi
country: Japan
facility: 1220.30.8102 Boehringer Ingelheim Investigational Site
city: Tanabe, Wakayama
country: Japan
facility: 1220.30.8115 Boehringer Ingelheim Investigational Site
city: Tsuchiura, Ibaraki
country: Japan
facility: 1220.30.8104 Boehringer Ingelheim Investigational Site
city: Aveiro
country: Portugal
facility: 1220.30.3503 Boehringer Ingelheim Investigational Site
city: Barreiro
country: Portugal
facility: 1220.30.3509 Boehringer Ingelheim Investigational Site
city: Coimbra
country: Portugal
facility: 1220.30.3506 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1220.30.3501 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1220.30.3505 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 1220.30.3507 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 1220.30.3502 Boehringer Ingelheim Investigational Site
city: Vila Real
country: Portugal
facility: 1220.30.3504 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.30.4001 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.30.4002 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.30.4003 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1220.30.4004 Boehringer Ingelheim Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: 1220.30.7002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1220.30.7001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1220.30.7004 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1220.30.7005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1220.30.7006 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1220.30.7007 Boehringer Ingelheim Investigational Site
city: A Coruña
country: Spain
facility: 1220.30.3406 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.30.3402 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1220.30.3404 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1220.30.3405 Boehringer Ingelheim Investigational Site
city: Santander
country: Spain
facility: 1220.30.3408 Boehringer Ingelheim Investigational Site
city: Sevilla
country: Spain
facility: 1220.30.3403 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 1220.30.3401 Boehringer Ingelheim Investigational Site
city: Vigo (Pontevedra)
country: Spain
facility: 1220.30.3407 Boehringer Ingelheim Investigational Site
city: Bern
country: Switzerland
facility: 1220.30.4106 Boehringer Ingelheim Investigational Site
city: La Chaux-de-Fonds
country: Switzerland
facility: 1220.30.4103 Boehringer Ingelheim Investigational Site
city: Lugano
country: Switzerland
facility: 1220.30.4107 Boehringer Ingelheim Investigational Site
city: St. Gallen
country: Switzerland
facility: 1220.30.4108 Boehringer Ingelheim Investigational Site
city: Zürich
country: Switzerland
facility: 1220.30.4101 Boehringer Ingelheim Investigational Site
city: Bristol
country: United Kingdom
facility: 1220.30.4405 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.30.4404 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.30.4409 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1220.30.4410 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 1220.30.4401 Boehringer Ingelheim Investigational Site
city: Nottingham
country: United Kingdom
facility: 1220.30.4408 Boehringer Ingelheim Investigational Site
city: Oxford
country: United Kingdom
facility: 1220.30.4407 Boehringer Ingelheim Investigational Site
city: Southampton
country: United Kingdom
facility: 1220.30.4403 Boehringer Ingelheim Investigational Site
city: Whitechapel, London
country: United Kingdom
facility: 1220.30.4406 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Jensen DM, Asselah T, Dieterich D, Foster GR, Sulkowski MS, Zeuzem S, Mantry P, Yoshida EM, Moreno C, Ouzan D, Wright M, Morano LE, Buynak R, Bourliere M, Hassanein T, Nishiguchi S, Kao JH, Omata M, Paik SW, Wong DK, Tam E, Kaita K, Feinman SV, Stern JO, Scherer J, Quinson AM, Voss F, Gallivan JP, Bocher WO, Ferenci P. Faldaprevir, pegylated interferon, and ribavirin for treatment-naive HCV genotype-1: pooled analysis of two phase 3 trials. Ann Hepatol. 2016 May-Jun;15(3):333-49. doi: 10.5604/16652681.1198803.
citation: Dieterich D, Nelson M, Soriano V, Arasteh K, Guardiola JM, Rockstroh JK, Bhagani S, Laguno M, Tural C, Ingiliz P, Jain MK, Stern JO, Manero M, Vinisko R, Kort J; STARTVerso4 study group. Faldaprevir and pegylated interferon alpha-2a/ribavirin in individuals co-infected with hepatitis C virus genotype-1 and HIV. AIDS. 2015 Mar 13;29(5):571-81. doi: 10.1097/QAD.0000000000000579.
citation: Ferenci P, Asselah T, Foster GR, Zeuzem S, Sarrazin C, Moreno C, Ouzan D, Maevskaya M, Calinas F, Morano LE, Crespo J, Dufour JF, Bourliere M, Agarwal K, Forton D, Schuchmann M, Zehnter E, Nishiguchi S, Omata M, Kukolj G, Datsenko Y, Garcia M, Scherer J, Quinson AM, Stern JO; STARTVerso1 Study Group. STARTVerso1: A randomized trial of faldaprevir plus pegylated interferon/ribavirin for chronic HCV genotype-1 infection. J Hepatol. 2015 Jun;62(6):1246-55. doi: 10.1016/j.jhep.2014.12.024. Epub 2015 Jan 2.