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)

NCT ID: NCT01343888

Last Updated: 2015-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 656 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2014-03-31

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.

Conditions

Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PegIFN/RBV

PegIFN/RBV for 48 weeks

Group Type: ACTIVE_COMPARATOR

PegIFN/RBV

Intervention Type: DRUG

PegIFN/RBV for 48 weeks

BI 201335 for 12 or 24 weeks

BI 201335 once daily low dose for 12 or 24 weeks in combination with PegIFN/RBV for 24 or 48 weeks

Group Type: EXPERIMENTAL

PegIFN/RBV

Intervention Type: DRUG

PegIFN/RBV for 48 weeks

BI 201335

Intervention Type: DRUG

BI 201335 once daily high dose

BI 201335

Intervention Type: DRUG

BI 201335 once daily low dose

Placebo and PegIFN/RBV

Placebo (oral) once daily plus PegIFN/RBV (subcutaneous injection/oral) for 24 weeks, followed by PegIFN/RBV alone up to Week 48.

Group Type: ACTIVE_COMPARATOR

PegIFN/RBV

Intervention Type: DRUG

PegIFN/RBV for 48 weeks

Placebo

Intervention Type: DRUG

Interventions

PegIFN/RBV

PegIFN/RBV for 48 weeks

Intervention Type: DRUG

BI 201335

BI 201335 once daily high dose

Intervention Type: DRUG

BI 201335

BI 201335 once daily low dose

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1220.30.4303 Boehringer Ingelheim Investigational Site

Linz, , Austria

1220.30.4301 Boehringer Ingelheim Investigational Site

Vienna, , Austria

1220.30.4302 Boehringer Ingelheim Investigational Site

Vienna, , Austria

1220.30.4304 Boehringer Ingelheim Investigational Site

Vienna, , Austria

1220.30.3201 Boehringer Ingelheim Investigational Site

Brussels, , Belgium

1220.30.3207 Boehringer Ingelheim Investigational Site

Brussels, , Belgium

1220.30.3204 Boehringer Ingelheim Investigational Site

Edegem, , Belgium

1220.30.3205 Boehringer Ingelheim Investigational Site

Ghent, , Belgium

1220.30.3202 Boehringer Ingelheim Investigational Site

Leuven, , Belgium

1220.30.3203 Boehringer Ingelheim Investigational Site

Liège, , Belgium

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, , France

1220.30.3302 Boehringer Ingelheim Investigational Site

Paris, , France

1220.30.3309 Boehringer Ingelheim Investigational Site

Paris, , France

1220.30.3316 Boehringer Ingelheim Investigational Site

Pessac, , France

1220.30.3315 Boehringer Ingelheim Investigational Site

Rennes, , France

1220.30.3312 Boehringer Ingelheim Investigational Site

Saint-Laurent-du-Var, , France

1220.30.3313 Boehringer Ingelheim Investigational Site

Toulouse, , France

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, , Germany

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, , Japan

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

Lisbon, , Portugal

1220.30.3505 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

1220.30.3507 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

1220.30.3502 Boehringer Ingelheim Investigational Site

Porto, , Portugal

1220.30.3504 Boehringer Ingelheim Investigational Site

Vila Real, , Portugal

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, , Romania

1220.30.7002 Boehringer Ingelheim Investigational Site

Chelyabinsk, , Russia

1220.30.7001 Boehringer Ingelheim Investigational Site

Moscow, , Russia

1220.30.7004 Boehringer Ingelheim Investigational Site

Moscow, , Russia

1220.30.7005 Boehringer Ingelheim Investigational Site

Moscow, , Russia

1220.30.7006 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

1220.30.7007 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

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

Seville, , Spain

1220.30.3401 Boehringer Ingelheim Investigational Site

Valencia, , Spain

1220.30.3407 Boehringer Ingelheim Investigational Site

Vigo (Pontevedra), , Spain

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

Sankt Gallen, , Switzerland

1220.30.4101 Boehringer Ingelheim Investigational Site

Zurich, , Switzerland

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, , United Kingdom

Countries

Austria; Belgium; France; Germany; Japan; Portugal; Romania; Russia; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 27049487 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25710287 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25559324 (View on PubMed)

Other Identifiers

2010-021716-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1220.30

Identifier Type: -

Identifier Source: org_study_id