Japanese Pegylated Interferon (PegIFN) Alfa-2b/Ribavirin (RBV) Combination Trial

Safety, Efficacy and Pharmacokinetics of BI 201335 NA in Patient With Genotype 1 Chronic Hepatitis C Virus Infection in Combination With Pegylated Interferon Alfa-2b and Ribavirin - Cohort 1 for Treatment-naive Patients: Randomised, Double-blind Part of BI 201335 NA for 12 or 24 Weeks - Cohort 2 for Treatment-experienced Patients: Open-label Part of BI 201335 NA for 24 Weeks

The aim of this trial is to evaluate the safety and efficacy of BI 201335 given for 12 or 24 weeks in combination with PegIFN alfa-2b/RBV given for 24 or 48 weeks in chronic genotype 1 hepatitis C virus infected treatment-naïve and treatment-experienced Japanese patients

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: BI 201335 low dose; Drug: BI 201335 high dose

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku, Chiba, Japan
    • 1220.54.08104 Boehringer Ingelheim Investigational Site
  • Chuo-ku, Kobe, Hyogo, Japan
    • 1220.54.08118 Boehringer Ingelheim Investigational Site
  • Fukui, Fukui, Japan
    • 1220.54.08108 Boehringer Ingelheim Investigational Site
  • Gifu, Gifu, Japan
    • 1220.54.08110 Boehringer Ingelheim Investigational Site
  • Itabashi-ku, Tokyo, Japan
    • 1220.54.08105 Boehringer Ingelheim Investigational Site
  • Izunokuni, Shizuoka, Japan
    • 1220.54.08112 Boehringer Ingelheim Investigational Site
  • Kanazawa, Ishikawa, Japan
    • 1220.54.08107 Boehringer Ingelheim Investigational Site
  • Kita-gun, Kagawa, Japan
    • 1220.54.08120 Boehringer Ingelheim Investigational Site
  • Kofu, Yamanashi, Japan
    • 1220.54.08109 Boehringer Ingelheim Investigational Site
  • Kurume, Fukuoka, Japan
    • 1220.54.08123 Boehringer Ingelheim Investigational Site
  • Mtsuyama, Ehime, Japan
    • 1220.54.08121 Boehringer Ingelheim Investigational Site
  • Nagoya, Aichi, Japan
    • 1220.54.08113 Boehringer Ingelheim Investigational Site
  • Nishinomiya, Hyogo, Japan
    • 1220.54.08117 Boehringer Ingelheim Investigational Site
  • Ogaki, Gifu, Japan
    • 1220.54.08111 Boehringer Ingelheim Investigational Site
  • Oo mura, Nagasaki,, Japan
    • 1220.54.08124 Boehringer Ingelheim Investigational Site
  • Osaka, Osaka, Japan
    • 1220.54.08115 Boehringer Ingelheim Investigational Site
  • Osakasayama, Osaka, Japan
    • 1220.54.08116 Boehringer Ingelheim Investigational Site
  • Sapporo, Hokkaido, Japan
    • 1220.54.08101 Boehringer Ingelheim Investigational Site
  • Sendai, Miyagi, Japan
    • 1220.54.08102 Boehringer Ingelheim Investigational Site
  • Tanabe, Wakayama, Japan
    • 1220.54.08119 Boehringer Ingelheim Investigational Site
  • Toyama,Toyama, Japan
    • 1220.54.08106 Boehringer Ingelheim Investigational Site
  • Tsu, Mie, Japan
    • 1220.54.08114 Boehringer Ingelheim Investigational Site
  • Yahatanishi-ku, Kitakyusyu, Fukuoka, Japan
    • 1220.54.08122 Boehringer Ingelheim Investigational Site
  • Yamagata, Yamagata, Japan
    • 1220.54.08125 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

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

   • positive anti-HCV antibodies or detected HCV RNA at least 6 months before screening; or,
   • liver biopsy consistent with chronic HCV infection.
2. HCV genotype 1 infection confirmed by genotypic testing at screening
3. (For Cohort 1 only) Therapy-naïve to interferon, pegylated interferon, and ribavirin (For Cohort 2 only) Confirmed prior virological failure (null response, partial response, breakthrough or relapse) with an approved dose of PegIFN alfa/RBV or IFN beta/RBV for at least 12 weeks and with an 8-week washout period before screening
4. HCV RNA = 100,000 IU/mL at screening
5. Documentation of a liver biopsy within 3 years or fibroscan within 6 months before randomization (Visit 2)
6. Age 20 to 70 years

7. Female patients who are infertile or who are of childbearing potential with a negative pregnancy test and agreeing to use one accepted method of birth control in addition to the use of a condom by their male partners.

   or Male patients who are infertile, who are without pregnant female partners or who consistently and correctly use condoms.

8. Signed informed consent form before 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. Steatosis diagnosed incidentally (e.g. by biopsy) without clinical relevance is not an exclusion criterion.
3. HIV co-infection,
4. Hepatitis B virus (HBV) infection based on presence of hepatitis B surface antigen (HBsAg),
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 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 patient's 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 screening. 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 (Stronger Neo-Minophagen C; SNMC), or Sho-saiko-to (SST) within 28 days prior to randomization (Visit 2) and throughout the treatment phase of this trial,
11. (For Cohort 2 only) Patients who have been previously treated with at least one dose of any antiviral or immunomodulatory drug other than (pegylated) interferon alfa, interferon beta or ribavirin for acute or chronic HCV infection including and not restricted to protease or polymerase inhibitors,
12. Known hypersensitivity to any ingredient of the study drugs,
13. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1. BI 201335 low dose plus PegIFN/RBV; low dose BI 201335 NA once daily for 12 or 24 weeks combined with PegIFN/RBV for 24 or 48 weeks in treatment-naive patients	Drug: BI 201335 low dose; BI 201335 low dose with PegIFN/RBV
Experimental: 2. BI 201335 high dose plus PegIFN/RBV; high dose BI 201335 NA once daily for 12 weeks combined with PegIFN/RBV for 24 or 48 weeks in treatment-naive patients	Drug: BI 201335 high dose; BI 201335 high dose with PegIFN/RBV
Experimental: 3. BI 201335 high dose plus PegIFN/RBV; high dose BI 201335 NA once daily for 24 weeks combined with PegIFN/RBV for 24 or 48 weeks in treatment-experienced (relapser) patients	Drug: BI 201335 high dose; BI 201335 high dose with PegIFN/RBV
Experimental: 4. BI 201335 high dose plus PegIFN/RBV; high dose BI 201335 NA once daily for 24 weeks combined with PegIFN/RBV for 48 weeks in treatment-experienced (null responder, partial responder, breakthrough) patients	Drug: BI 201335 high dose; BI 201335 high dose with PegIFN/RBV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Investigator Defined Drug-related Adverse Events	Drug-related AEs were defined as those whose causal relationship with any one of the investigational products was considered by the investigator.	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained Virological Response (SVR12), Defined as Plasma HCV RNA Undetectable at 12 Weeks After End of Treatment (EOT)	Plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level <25 IU/mL (undetected) 12 weeks after the originally planned treatment duration	EOT (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60)
Sustained Virological Response (SVR24), Defined as Plasma HCV RNA Undetectable at 24 Weeks After End of Treatment (EOT)	Plasma HCV RNA level <25 IU/mL (undetected) 24 weeks after the originally planned treatment duration	EOT (up to Week 24 or 48) and 24 weeks after the EOT (up to Week 48 or 72)
Early Treatment Success (ETS), Defined as Plasma HCV RNA <25 IU/mL at Week 4 and HCV RNA Undetectable at Week 8	Plasma HCV RNA level <25 IU/mL (detected or undetected) at Week 4 and HCV RNA <25 IU/mL (undetected) at Week 8	up to 8 weeks
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	EOT (up to Week 24 or 48)
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	EOT (up to Week 24 or 48)
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. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks after the EOT (up to Week 36 or 60)
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. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks after the EOT (up to Week 36 or 60)
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	EOT (up to Week 24 or 48)
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	EOT (up to Week 24 or 48)
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. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks after the EOT (up to Week 36 or 60)
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. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline	12 weeks after the EOT (up to Week 36 or 60)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Nishiguchi S, Urano Y, Suzaki K, Taniguchi A, Scherer J, Berger KL, Quinson AM, Stern JO, Omata M. Safety and efficacy of faldaprevir in combination with pegylated interferon alpha-2b and ribavirin in Japanese patients with genotype-1 chronic hepatitis C virus infection. Hepatol Res. 2017 Mar;47(3):E142-E151. doi: 10.1111/hepr.12741. Epub 2016 Aug 10.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: April 12, 2012
• First Submitted That Met QC Criteria: April 17, 2012
• First Posted (Estimate): April 18, 2012

Study Record Updates

• Last Update Posted (Estimate): August 3, 2015
• Last Update Submitted That Met QC Criteria: July 3, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C
• Other Study ID Numbers: 1220.54