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

NCT01132313 | Completed Phase 2 Results

• 2 other identifiers: 1241.212009-018197-66
• Study Type: interventional
• Target: 488
• Locations: 9 countries
• Sites: 50

Brief Summary

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)

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (3)

• Part 1: Rapid Virological Response (RVR)

  Part 1: Rapid virological response (RVR), defined as Hepatitis C Virus Ribonucleic acid (HCV RNA) \<25IU/mL at Week 4 of treatment

  4 weeks

• Part 2: Sustained Virological Response (SVR)

  Part 2: Sustained virological response (SVR), defined as HCV RNA \<25 IU/mL and undetectable at 12 weeks after end of treatment

  From drug administration until 12 weeks after end of treatment, up to 52 weeks

• Part 3 and 4: Sustained Virological Response (SVR)

  Part 3 and 4: Sustained virological response (SVR) defined as HCV RNA \<25IU/mL and undetectable at 12 weeks after end of treatment

  From drug administration until 12 weeks after end of treatment, up to 36 weeks

Secondary Outcomes (6)

• Part 1: Time to Virological Response

  From drug administration until end of drug administration, up to 4 weeks

• Part 2: Time to Virological Response

  From drug administration until end of drug administration, up to 40 weeks

• Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4

  4 weeks

• Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment

  4 weeks and 24 weeks after the end of treatment, up to 64 weeks

• Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment

  Week 4 and 12

Study Arms (12)

2

EXPERIMENTAL

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

Drug: Ribavirin; Drug: BI 201335; Drug: BI 207127

1

EXPERIMENTAL

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

Drug: BI 207127; Drug: BI 201335; Drug: Ribavirin

3

EXPERIMENTAL

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

Drug: BI 207127; Drug: BI 201335; Drug: Ribavirin

4

EXPERIMENTAL

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

Drug: BI 207127; Drug: Ribavirin; Drug: BI 201335

5

EXPERIMENTAL

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

Drug: BI 201335; Drug: BI 207127; Drug: Ribavirin

6

EXPERIMENTAL

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

Drug: Ribavirin; Drug: BI 201335; Drug: BI 207217

7

EXPERIMENTAL

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

Drug: BI 207127; Drug: BI 201335

8

EXPERIMENTAL

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

Drug: BI 207127; Drug: Ribavirin; Drug: BI 201335

9

EXPERIMENTAL

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

Drug: BI 207127; Drug: BI 201335; Drug: Ribavirin

10

EXPERIMENTAL

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

Drug: BI 201335; Drug: BI 207127; Drug: Ribavirin

11

EXPERIMENTAL

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

Drug: Ribavirin; Drug: BI 207127; Drug: BI 201335

12

EXPERIMENTAL

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

Drug: Ribavirin; Drug: BI 201335; Drug: BI 207127

Interventions

BI 207127 DRUG

28 weeks, high dose, TID

4

BI 201335 DRUG

40 weeks, QD

5

Ribavirin DRUG

16 weeks, according to label

11

BI 207217 DRUG

28 weeks, high dose BID

6

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (53)

1241.21.0003 Boehringer Ingelheim Investigational Site

La Jolla, California, United States

Location

1241.21.0006 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Location

1241.21.0004 Boehringer Ingelheim Investigational Site

San Francisco, California, United States

Location

1241.21.0011 Boehringer Ingelheim Investigational Site

Palm Harbor, Florida, United States

Location

1241.21.0013 Boehringer Ingelheim Investigational Site

Valparaiso, Indiana, United States

Location

1241.21.0008 Boehringer Ingelheim Investigational Site

Springfield, Massachusetts, United States

Location

1241.21.0019 Boehringer Ingelheim Investigational Site

Fayetteville, North Carolina, United States

Location

1241.21.0012 Boehringer Ingelheim Investigational Site

Arlington, Texas, United States

Location

1241.21.0005 Boehringer Ingelheim Investigational Site

Austin, Texas, United States

Location

1241.21.0007 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

Location

1241.21.0010 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1241.21.0017 Boehringer Ingelheim Investigational Site

Seattle, Washington, United States

Location

1241.21.61002 Boehringer Ingelheim Investigational Site

Heidelberg, Victoria, Australia

Location

1241.21.61001 Boehringer Ingelheim Investigational Site

Melbourne, Victoria, Australia

Location

1241.21.43003 Boehringer Ingelheim Investigational Site

Linz, Austria

Location

1241.21.43001 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1241.21.43002 Boehringer Ingelheim Investigational Site

Vienna, Austria

Location

1241.21.33005 Boehringer Ingelheim Investigational Site

Clichy, France

Location

1241.21.33007 Boehringer Ingelheim Investigational Site

Grenoble Cédex 9, France

Location

1241.21.33003 Boehringer Ingelheim Investigational Site

Lyon, France

Location

1241.21.33001 Boehringer Ingelheim Investigational Site

Marseille, France

Location

1241.21.33002 Boehringer Ingelheim Investigational Site

Montpellier, France

Location

1241.21.33004 Boehringer Ingelheim Investigational Site

Paris, France

Location

1241.21.33008 Boehringer Ingelheim Investigational Site

Paris, France

Location

1241.21.33006 Boehringer Ingelheim Investigational Site

Vandœuvre-lès-Nancy, France

Location

1241.21.49002 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1241.21.49003 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1241.21.49007 Boehringer Ingelheim Investigational Site

Düsseldorf, Germany

Location

1241.21.49005 Boehringer Ingelheim Investigational Site

Esslingen am Neckar, Germany

Location

1241.21.49001 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1241.21.49006 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

1241.21.49009 Boehringer Ingelheim Investigational Site

Hanover, Germany

Location

1241.21.49004 Boehringer Ingelheim Investigational Site

Leipzig, Germany

Location

1241.21.49008 Boehringer Ingelheim Investigational Site

Mainz, Germany

Location

1241.21.64001 Boehringer Ingelheim Investigational Site

Auckland NZ, New Zealand

Location

1241.21.35103 Boehringer Ingelheim Investigational Site

Aveiro, Portugal

Location

1241.21.35104 Boehringer Ingelheim Investigational Site

Coimbra, Portugal

Location

1241.21.35101 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1241.21.35105 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

1241.21.35102 Boehringer Ingelheim Investigational Site

Porto, Portugal

Location

1241.21.40001 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1241.21.40002 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1241.21.40003 Boehringer Ingelheim Investigational Site

Bucharest, Romania

Location

1241.21.34002 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1241.21.34005 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

1241.21.34003 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1241.21.34004 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

1241.21.34001 Boehringer Ingelheim Investigational Site

Majadahonda-Madrid, Spain

Location

1241.21.34006 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

1241.21.41003 Boehringer Ingelheim Investigational Site

Basel, Switzerland

Location

1241.21.41006 Boehringer Ingelheim Investigational Site

Bern, Switzerland

Location

1241.21.41001 Boehringer Ingelheim Investigational Site

Sankt Gallen, Switzerland

Location

1241.21.41002 Boehringer Ingelheim Investigational Site

Zurich, Switzerland

Location

Related Publications (5)

• 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.

  PMID: 27140229 DERIVED

• 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.

  PMID: 26650626 DERIVED

• 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.

  PMID: 25512403 DERIVED

• 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.

  PMID: 23944300 DERIVED

• 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.

  PMID: 23558093 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

deleobuvir; faldaprevir; Ribavirin

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

There were only 3 patients entered in part 4 of the trial, therefore no formal analyses of efficacy data were performed.

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2010
• First Posted: May 28, 2010
• Study Start: May 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: February 1, 2016
• Results First Posted: February 1, 2016

Record last verified: 2015-12

Locations

US (12); AU (2); RO (3); DE (9); FR (8); NZ (1); PT (5); ES (6); CH (4)