Safety, Antiviral Effect and PK of BI 207127 + BI 201335 +/- RBV for 4 up to 40 Weeks in Patients With Chronic HCV Genotype 1 Infection

NCT ID: NCT01132313

Last Updated: 2016-02-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

488 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2014-10-31

Brief Summary

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The substances BI 201335 and BI 207127 are being developed for the treatment of chronic hepatitis C virus infection. BI 201335 and BI 207127 work by preventing the virus from replicating.

The currently available medications pegylated interferon alfa and ribavirin for hepatitis C ca have considerable adverse events in patients and in many cases are not sufficiently effective. This is particularly the case in treatment of patients infected with genotype 1 of HCV.

A combination therapy of these new substances without pegylated interferon alfa may be associated with fewer adverse events that currently available (pegylated interferon-alfa-based) medication and may also provide a treatment option to the large number of patients with contraindications or intolerance to pegylated interferon alfa.

This clinical trial (1241.21) currently consists of 3 distinct studies: Part 1, Part 2 and Part 3.

Part 1 (SOUND-C1) is a 2 armed study as described in experimental arms 1 and 2 below (actual enrollment: 56 patients; randomized and treated: 32) Part 2 (SOUND-C2) is a 5 armed study as described in experimental arms 3 to 7 below (actual enrollment: 465; randomized and treated: 362) Part 3 (SOUND-C3) includes 3 arms as described in experimental arms 8 to 10 below (83 patients randomized and treated)

Detailed Description

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Conditions

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Hepatitis C, Chronic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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2

4 weeks of high dose TID BI 207127 and QD BI 201335 in combination with RBV, Part 1

Group Type EXPERIMENTAL

Ribavirin

Intervention Type DRUG

48 weeks, according to label

BI 201335

Intervention Type DRUG

24 weeks, QD

BI 207127

Intervention Type DRUG

4 weeks, high dose, TID

1

4 weeks of low dose three times per day (TID) BI 207127 and once daily (QD) BI 201335 in combination with RBV, Part 1

Group Type EXPERIMENTAL

BI 207127

Intervention Type DRUG

4 weeks, low dose TID

BI 201335

Intervention Type DRUG

24 weeks, QD

Ribavirin

Intervention Type DRUG

48 weeks, according to label

3

16 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Group Type EXPERIMENTAL

BI 207127

Intervention Type DRUG

16 weeks, high dose, TID

BI 201335

Intervention Type DRUG

16 weeks, QD

Ribavirin

Intervention Type DRUG

16 weeks, according to label

4

28 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Group Type EXPERIMENTAL

BI 207127

Intervention Type DRUG

28 weeks, high dose, TID

Ribavirin

Intervention Type DRUG

28 weeks, according to label

BI 201335

Intervention Type DRUG

28 weeks, QD

5

40 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Group Type EXPERIMENTAL

BI 201335

Intervention Type DRUG

40 weeks, QD

BI 207127

Intervention Type DRUG

40 weeks, high dose, TID

Ribavirin

Intervention Type DRUG

40 weeks, according to label

6

28 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 2

Group Type EXPERIMENTAL

Ribavirin

Intervention Type DRUG

28 weeks, according to label

BI 201335

Intervention Type DRUG

28 weeks, QD

BI 207217

Intervention Type DRUG

28 weeks, high dose BID

7

28 weeks of TID BI 207127 and QD BI 201335 without RBV, Part 2

Group Type EXPERIMENTAL

BI 207127

Intervention Type DRUG

28 weeks, high dose, TID

BI 201335

Intervention Type DRUG

28 weeks, QD

8

16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3

Group Type EXPERIMENTAL

BI 207127

Intervention Type DRUG

16 weeks, high dose, BID

Ribavirin

Intervention Type DRUG

16 weeks, according to label

BI 201335

Intervention Type DRUG

16 weeks, QD

9

24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 3

Group Type EXPERIMENTAL

BI 207127

Intervention Type DRUG

24 weeks, very high dose, BID

BI 201335

Intervention Type DRUG

24 weeks, QD

Ribavirin

Intervention Type DRUG

24 weeks, according to label

10

24 weeks of TID BI 207127 and QD BI 201335 in combination with RBV, Part 3

Group Type EXPERIMENTAL

BI 201335

Intervention Type DRUG

24 weeks, QD

BI 207127

Intervention Type DRUG

24 weeks, high dose, TID

Ribavirin

Intervention Type DRUG

24 weeks, according to label

11

16 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4

Group Type EXPERIMENTAL

Ribavirin

Intervention Type DRUG

16 weeks, according to label

BI 207127

Intervention Type DRUG

16 weeks, standard dose, BID

BI 201335

Intervention Type DRUG

16 weeks, QD

12

24 weeks of BID BI 207127 and QD BI 201335 in combination with RBV, Part 4

Group Type EXPERIMENTAL

Ribavirin

Intervention Type DRUG

24 weeks, according to label

BI 201335

Intervention Type DRUG

24 weeks, QD

BI 207127

Intervention Type DRUG

24 weeks, standard dose, BID

Interventions

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BI 207127

28 weeks, high dose, TID

Intervention Type DRUG

BI 201335

40 weeks, QD

Intervention Type DRUG

BI 207127

4 weeks, low dose TID

Intervention Type DRUG

BI 201335

24 weeks, QD

Intervention Type DRUG

Ribavirin

16 weeks, according to label

Intervention Type DRUG

Ribavirin

28 weeks, according to label

Intervention Type DRUG

Ribavirin

28 weeks, according to label

Intervention Type DRUG

BI 207127

40 weeks, high dose, TID

Intervention Type DRUG

BI 207127

24 weeks, very high dose, BID

Intervention Type DRUG

BI 207127

16 weeks, standard dose, BID

Intervention Type DRUG

BI 201335

24 weeks, QD

Intervention Type DRUG

Ribavirin

48 weeks, according to label

Intervention Type DRUG

Ribavirin

40 weeks, according to label

Intervention Type DRUG

BI 207127

16 weeks, high dose, TID

Intervention Type DRUG

BI 207127

28 weeks, high dose, TID

Intervention Type DRUG

BI 201335

28 weeks, QD

Intervention Type DRUG

BI 201335

16 weeks, QD

Intervention Type DRUG

Ribavirin

24 weeks, according to label

Intervention Type DRUG

BI 201335

24 weeks, QD

Intervention Type DRUG

BI 201335

28 weeks, QD

Intervention Type DRUG

BI 207127

24 weeks, standard dose, BID

Intervention Type DRUG

BI 201335

24 weeks, QD

Intervention Type DRUG

BI 201335

16 weeks, QD

Intervention Type DRUG

BI 207127

16 weeks, high dose, BID

Intervention Type DRUG

BI 201335

24 weeks, QD

Intervention Type DRUG

Ribavirin

16 weeks, according to label

Intervention Type DRUG

Ribavirin

16 weeks, according to label

Intervention Type DRUG

BI 207217

28 weeks, high dose BID

Intervention Type DRUG

BI 201335

16 weeks, QD

Intervention Type DRUG

BI 207127

24 weeks, high dose, TID

Intervention Type DRUG

Ribavirin

48 weeks, according to label

Intervention Type DRUG

BI 207127

4 weeks, high dose, TID

Intervention Type DRUG

BI 201335

28 weeks, QD

Intervention Type DRUG

Ribavirin

24 weeks, according to label

Intervention Type DRUG

Ribavirin

24 weeks, according to label

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Chronic hepatitis C virus (HCV) infection of genotype (GT) 1
* Parts 1-3:Treatment naive to Interferon -alfa (IFN), Pegylated interferon -alfa (PegIFN), ribavirin (RBV), and any direct acting antiviral agent for chronic hepatitis C
* Part 4: Treatment experienced with confirmed prior virological failure to an approved dose of PegIFN/RBV (null-response)
* HCV RNA \>=10,000 IU/mL at screening
* Liver biopsy within two years or fibroscan within six months prior to baseline
* Liver biopsy within two years or fibroscan within 6 months prior to screening
* Age 18-75 years

Exclusion Criteria

* Hepatitis C virus (HCV) infection of mixed genotype
* Evidence of liver disease due to causes other than chronic HCV infection
* Positive ELISA for human immunodeficiency virus (HIV)
* Hepatitis B virus (HBV) infection
* Decompensated liver disease or history of decompensated liver disease
* Active or suspected malignancy within the last 5 years
* Ongoing or historical photosensitivity or recurrent rash
* History of alcohol or drug abuse (except cannabis) within the past 12 months
* Body mass index (BMI)I \<18 or \> 35 kg/m2
* Usage of any investigational drugs within 30 days prior to enrolment, or 5 half-lives, whichever is longer; o the planned usage of an investigational drug during the course of the current study
* Known hypersensitivity to any ingredient of the study drugs
* A condition that is defined as one which in the opinion of the investigator may interfere with the patient's capability for participation in the trial or may influence the results of the trial
* Alpha fetoprotein \>100ng/mL at screening; if \>20ng/mL and \<=100ng/mL, patients can be included if there is no evidence of liver cancer in an appropriate imaging study within 6 months prior to randomisation
* Total bilirubin \> 2 mg/dL with ratio of direct/indirect \> 1
* AST or ALT \>5xULN
* INR prolonged to \>1.7xULN
* Requirement for chronic systemic corticosteroids
* Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to enrolment or 5 half-lives, whichever is longer
* Received silymarin or glycyrrhizin or Sho-saiko-to within 30 days prior to enrolment
* Contraindications pertaining to PegIFN or RBV
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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1241.21.0003 Boehringer Ingelheim Investigational Site

La Jolla, California, United States

Site Status

1241.21.0006 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Site Status

1241.21.0004 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

Site Status

1241.21.0011 Boehringer Ingelheim Investigational Site

Palm Harbor, Florida, United States

Site Status

1241.21.0013 Boehringer Ingelheim Investigational Site

Valparaiso, Indiana, United States

Site Status

1241.21.0008 Boehringer Ingelheim Investigational Site

Springfield, Massachusetts, United States

Site Status

1241.21.0019 Boehringer Ingelheim Investigational Site

Fayetteville, North Carolina, United States

Site Status

1241.21.0012 Boehringer Ingelheim Investigational Site

Arlington, Texas, United States

Site Status

1241.21.0005 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

Site Status

1241.21.0007 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

Site Status

1241.21.0010 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Site Status

1241.21.0017 Boehringer Ingelheim Investigational Site

Seattle, Washington, United States

Site Status

1241.21.61002 Boehringer Ingelheim Investigational Site

Heidelberg, Victoria, Australia

Site Status

1241.21.61001 Boehringer Ingelheim Investigational Site

Melbourne, Victoria, Australia

Site Status

1241.21.43003 Boehringer Ingelheim Investigational Site

Linz, , Austria

Site Status

1241.21.43001 Boehringer Ingelheim Investigational Site

Vienna, , Austria

Site Status

1241.21.43002 Boehringer Ingelheim Investigational Site

Vienna, , Austria

Site Status

1241.21.33005 Boehringer Ingelheim Investigational Site

Clichy, , France

Site Status

1241.21.33007 Boehringer Ingelheim Investigational Site

Grenoble Cédex 9, , France

Site Status

1241.21.33003 Boehringer Ingelheim Investigational Site

Lyon, , France

Site Status

1241.21.33001 Boehringer Ingelheim Investigational Site

Marseille, , France

Site Status

1241.21.33002 Boehringer Ingelheim Investigational Site

Montpellier, , France

Site Status

1241.21.33004 Boehringer Ingelheim Investigational Site

Paris, , France

Site Status

1241.21.33008 Boehringer Ingelheim Investigational Site

Paris, , France

Site Status

1241.21.33006 Boehringer Ingelheim Investigational Site

Vandœuvre-lès-Nancy, , France

Site Status

1241.21.49002 Boehringer Ingelheim Investigational Site

Berlin, , Germany

Site Status

1241.21.49003 Boehringer Ingelheim Investigational Site

Berlin, , Germany

Site Status

1241.21.49007 Boehringer Ingelheim Investigational Site

Düsseldorf, , Germany

Site Status

1241.21.49005 Boehringer Ingelheim Investigational Site

Esslingen am Neckar, , Germany

Site Status

1241.21.49001 Boehringer Ingelheim Investigational Site

Frankfurt am Main, , Germany

Site Status

1241.21.49006 Boehringer Ingelheim Investigational Site

Hamburg, , Germany

Site Status

1241.21.49009 Boehringer Ingelheim Investigational Site

Hanover, , Germany

Site Status

1241.21.49004 Boehringer Ingelheim Investigational Site

Leipzig, , Germany

Site Status

1241.21.49008 Boehringer Ingelheim Investigational Site

Mainz, , Germany

Site Status

1241.21.64001 Boehringer Ingelheim Investigational Site

Auckland NZ, , New Zealand

Site Status

1241.21.35103 Boehringer Ingelheim Investigational Site

Aveiro, , Portugal

Site Status

1241.21.35104 Boehringer Ingelheim Investigational Site

Coimbra, , Portugal

Site Status

1241.21.35101 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

Site Status

1241.21.35105 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

Site Status

1241.21.35102 Boehringer Ingelheim Investigational Site

Porto, , Portugal

Site Status

1241.21.40001 Boehringer Ingelheim Investigational Site

Bucharest, , Romania

Site Status

1241.21.40002 Boehringer Ingelheim Investigational Site

Bucharest, , Romania

Site Status

1241.21.40003 Boehringer Ingelheim Investigational Site

Bucharest, , Romania

Site Status

1241.21.34002 Boehringer Ingelheim Investigational Site

Barcelona, , Spain

Site Status

1241.21.34005 Boehringer Ingelheim Investigational Site

Barcelona, , Spain

Site Status

1241.21.34003 Boehringer Ingelheim Investigational Site

Madrid, , Spain

Site Status

1241.21.34004 Boehringer Ingelheim Investigational Site

Madrid, , Spain

Site Status

1241.21.34001 Boehringer Ingelheim Investigational Site

Majadahonda-Madrid, , Spain

Site Status

1241.21.34006 Boehringer Ingelheim Investigational Site

Valencia, , Spain

Site Status

1241.21.41003 Boehringer Ingelheim Investigational Site

Basel, , Switzerland

Site Status

1241.21.41006 Boehringer Ingelheim Investigational Site

Bern, , Switzerland

Site Status

1241.21.41001 Boehringer Ingelheim Investigational Site

Sankt Gallen, , Switzerland

Site Status

1241.21.41002 Boehringer Ingelheim Investigational Site

Zurich, , Switzerland

Site Status

Countries

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United States Australia Austria France Germany New Zealand Portugal Romania Spain Switzerland

References

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Zeuzem S, Mantry P, Soriano V, Buynak RJ, Dufour JF, Pockros PJ, Wright D, Angus P, Buti M, Stern JO, Kadus W, Vinisko R, Bocher W, Mensa FJ. Short article: Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study. Eur J Gastroenterol Hepatol. 2016 Aug;28(8):923-6. doi: 10.1097/MEG.0000000000000649.

Reference Type DERIVED
PMID: 27140229 (View on PubMed)

Asselah T, Zeuzem S, Soriano V, Bronowicki JP, Lohse AW, Mullhaupt B, Schuchmann M, Bourliere M, Buti M, Roberts SK, Gane EJ, Stern JO, Voss F, Baum P, Gallivan JP, Bocher WO, Mensa FJ. ITPA Genotypes Predict Anemia but Do Not Affect Virological Response with Interferon-Free Faldaprevir, Deleobuvir, and Ribavirin for HCV Infection. PLoS One. 2015 Dec 9;10(12):e0144004. doi: 10.1371/journal.pone.0144004. eCollection 2015.

Reference Type DERIVED
PMID: 26650626 (View on PubMed)

Zeuzem S, Soriano V, Asselah T, Gane EJ, Bronowicki JP, Angus P, Lohse AW, Stickel F, Mullhaupt B, Roberts S, Schuchmann M, Manns M, Bourliere M, Buti M, Stern JO, Gallivan JP, Voss F, Sabo JP, Bocher W, Mensa FJ; SOUND-C2 Study Group. Efficacy and safety of faldaprevir, deleobuvir, and ribavirin in treatment-naive patients with chronic hepatitis C virus infection and advanced liver fibrosis or cirrhosis. Antimicrob Agents Chemother. 2015 Feb;59(2):1282-91. doi: 10.1128/AAC.04383-14. Epub 2014 Dec 15.

Reference Type DERIVED
PMID: 25512403 (View on PubMed)

Zeuzem S, Soriano V, Asselah T, Bronowicki JP, Lohse AW, Mullhaupt B, Schuchmann M, Bourliere M, Buti M, Roberts SK, Gane EJ, Stern JO, Vinisko R, Kukolj G, Gallivan JP, Bocher WO, Mensa FJ. Faldaprevir and deleobuvir for HCV genotype 1 infection. N Engl J Med. 2013 Aug 15;369(7):630-9. doi: 10.1056/NEJMoa1213557.

Reference Type DERIVED
PMID: 23944300 (View on PubMed)

Zeuzem S, Asselah T, Angus P, Zarski JP, Larrey D, Mullhaupt B, Gane E, Schuchmann M, Lohse AW, Pol S, Bronowicki JP, Roberts S, Arasteh K, Zoulim F, Heim M, Stern JO, Nehmiz G, Kukolj G, Bocher WO, Mensa FJ. Faldaprevir (BI 201335), deleobuvir (BI 207127) and ribavirin oral therapy for treatment-naive HCV genotype 1: SOUND-C1 final results. Antivir Ther. 2013;18(8):1015-9. doi: 10.3851/IMP2567. Epub 2013 Apr 4.

Reference Type DERIVED
PMID: 23558093 (View on PubMed)

Other Identifiers

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2009-018197-66

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1241.21

Identifier Type: -

Identifier Source: org_study_id

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