Short Term Treatment With BI 201335, Peginterferon-alpha 2a and Ribavirin in Hepatitis c Virus Genotype-1 Treatment-naïve Patients (SILEN-C3)

Antiviral Effect and Safety of Once Daily BI 201335 NA in Hepatitis C Virus Genotype 1 Infected Treatment-naive Patients for 12 or 24 Weeks as Combination Therapy With Pegylated Interferon-alpha 2a and Ribavirin (Randomised, Open Label, Phase II)

To compare the antiviral efficacy and safety of a 12-week with a 24-week treatment of BI 201335 at a dose of 120 mg once daily, with a 24-week background of pegylated interferon-alpha 2a (PegIFN) plus ribavirin (RBV), in treatment-naïve patients infected with hepatitis C virus (HCV) genotype 1

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: BI 201335; Drug: Pegylated Interferon-alpha (IFN); Drug: Ribavirin (RBV)

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • 1220.40.4303 Boehringer Ingelheim Investigational Site
  • Wien, Austria
    • 1220.40.4301 Boehringer Ingelheim Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • 1220.40.1004 Boehringer Ingelheim Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • 1220.40.1001 Boehringer Ingelheim Investigational Site
  • Ontario
    • Ottawa, Ontario, Canada
      • 1220.40.1002 Boehringer Ingelheim Investigational Site
  • Quebec
    • Montreal, Quebec, Canada
      • 1220.40.1003 Boehringer Ingelheim Investigational Site
    • Montreal, Quebec, Canada
      • 1220.40.1005 Boehringer Ingelheim Investigational Site
• France
  • Clichy, France
    • 1220.40.3303A Boehringer Ingelheim Investigational Site
  • Lille, France
    • 1220.40.3305A Boehringer Ingelheim Investigational Site
  • Marseille, France
    • 1220.40.3301A Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • 1220.40.3306A Boehringer Ingelheim Investigational Site
  • Paris, France
    • 1220.40.3302A Boehringer Ingelheim Investigational Site
  • Rennes Cedex 09, France
    • 1220.40.3304A Boehringer Ingelheim Investigational Site
• Germany
  • Berlin, Germany
    • 1220.40.4902 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1220.40.4909 Boehringer Ingelheim Investigational Site
  • Düsseldorf, Germany
    • 1220.40.4906 Boehringer Ingelheim Investigational Site
  • Düsseldorf, Germany
    • 1220.40.4908 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1220.40.4904 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1220.40.4905 Boehringer Ingelheim Investigational Site
• Romania
  • Bucharest, Romania
    • 1220.40.4001 Boehringer Ingelheim Investigational Site
  • Bucharest, Romania
    • 1220.40.4002 Boehringer Ingelheim Investigational Site
  • Bucharest, Romania
    • 1220.40.4003 Boehringer Ingelheim Investigational Site
• United States
  • Mississippi
    • Tulepo, Mississippi, United States
      • 1220.40.002 Boehringer Ingelheim Investigational Site
  • New York
    • New York, New York, United States
      • 1220.40.007 Boehringer Ingelheim Investigational Site
  • Tennessee
    • Germantown, Tennessee, United States
      • 1220.40.006 Boehringer Ingelheim Investigational Site
    • Jackson, Tennessee, United States
      • 1220.40.004 Boehringer Ingelheim Investigational Site
    • Nashville, Tennessee, United States
      • 1220.40.003 Boehringer Ingelheim Investigational Site
  • Texas
    • Austin, Texas, United States
      • 1220.40.005 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Chronic hepatitis C infection of genotype 1
2. Therapy-naïve to interferon, pegylated interferon, and ribavirin
3. HCV viral load > 100.000 IU/ml at screening
4. Liver biopsy or fibroscan within two years prior to screening that provides evidence of any degree of fibrosis or cirrhosis
5. Normal retinal finding on fundoscopy within 6 months prior to Day 1
6. Age 18 to 70 years

Exclusion criteria:

1. HCV of mixed genotype (1/2, 1/3, and 1/4) .
2. Patients who have been previously treated with at least one dose of any protease inhibitor
3. Evidence of liver disease due to causes other than chronic HCV infection
4. Positive for HIV-1 or HIV-2 antibodies
5. Hepatitis B virus (HBV) infection
6. Decompensated liver disease, or history of decompensated liver disease
7. Active malignancy or history of malignancy within the last 5 years
8. History of alcohol or drug abuse (except cannabis) within the past 12 months.
9. Body Mass Index < 18 or > 35 kg/m2.
10. Usage of any investigational drugs within 30 days prior to enrolment
11. Alpha fetoprotein value >100ng/mL at screening;
12. Total bilirubin > 1.5 x ULN with ratio of direct/indirect > 1.
13. ALT or AST level > 10 x ULN

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: short arm; patients to receive BI201335 with PegIFN/RBV for 12 wks followed by 12 weeks PegIFN/RBV with a 3 days lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 NA 3 days after first administration of PegIFN/RBV)	Drug: BI 201335; BI 201335; Drug: Pegylated Interferon-alpha (IFN); Pegylated Interferon-alpha; Drug: Ribavirin (RBV); Ribavirin (RBV)
Experimental: long arm; patients to receive BI201335 with PegIFN/RBV for 24 wks with a 3 days lead-in phase of PegIFN/RBV (i.e. initiation of BI 201335 NA 3 days after first administration of PegIFN/RBV)	Drug: BI 201335; BI 201335; Drug: Pegylated Interferon-alpha (IFN); Pegylated Interferon-alpha; Drug: Ribavirin (RBV); Ribavirin (RBV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological Response at Week 28 (W28VR)	Virological response at Week 28: The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at Week 28.	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rapid Virological Response at Week 4 (RVR)	Rapid virological response at week 4 (RVR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 4.	4 weeks
Virological Response at Week 24 (W24VR)	virological response at week 24 (W24VR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 24.	24 weeks
Virological Response at Week 36 (W36VR)	Virological response at week 36 (W36VR): the patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at week 36.	36 weeks
End of Treatment Response (ETR)	End of Treatment Response (ETR): The patients who reached plasma hepatitis C virus ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at end of all therapy.	up to 48 weeks
Sustained Virological Response (SVR24) at 24 Weeks After Completion of All Therapy	Sustained Virological Response (SVR24) at 24 weeks: The patients who reached plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level below the lower limit of detection (BLD) at 24 weeks after completion of all Hepatitis C virus (HCV) therapy.	72 weeks
Viral Load (HCV RNA) at All Visits During Treatment and Follow-up	Viral load of Hepatitis C virus Ribonucleic acid (HCV RNA) at all visits during treatment (TRT) and follow-up, ie. change from baseline viral load at all visits.	From baseline to 72 weeks
Time to Reach a Plasma HCV RNA Level BLD While on Treatment	Time to reach a plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) level below the lower limit of detection (BLD) while on treatment	48 weeks
Laboratory Test Abnormalities and Study Medication Tolerabilities	Participants with possible clinically significant laboratory test abnormalities observed in functional groups: Haematology, Coagulation, Electrolytes, Enzymes, Substrates and Differentials, automatic.	48 weeks
Number of Participants With Clinically Relevant Abnormalities Vital Signs, and Physical Examination	No number of participants with clinically relevant abnormalities in vital signs and physical examination.	48 weeks
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (1)	Change from baseline (CFB) in Red blood cells.	baseline and 48 weeks
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (2)	Change from baseline (CFB) in haematocrit and Eosinophils.	baseline and 48 weeks
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (3)	Change from baseline (CFB) in Platelets and white blood cells.	baseline and 48 weeks
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (4)	Change from baseline (CFB) in Sodium, Bicarbonate, Cholesterol total, Triglyceride, and Glucose.	baseline and 48 weeks
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (5)	Change from baseline (CFB) in AST/GOT, ALT/GPT, Alka. phosphatase, GGT, Creatine kinase, Lipase, and Amylase.	baseline and 48 weeks
Laboratory Test Value Changes Over Time for Selected Lab Test Parameters (6)	Change from baseline (CFB) in PT-INR (ratio).	baseline and 48 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Dieterich D, Asselah T, Guyader D, Berg T, Schuchmann M, Mauss S, Ratziu V, Ferenci P, Larrey D, Maieron A, Stern JO, Ozan M, Datsenko Y, Bocher WO, Steinmann G. SILEN-C3, a phase 2 randomized trial with faldaprevir plus pegylated interferon alpha-2a and ribavirin in treatment-naive hepatitis C virus genotype 1-infected patients. Antimicrob Agents Chemother. 2014 Jun;58(6):3429-36. doi: 10.1128/AAC.02497-13. Epub 2014 Apr 7.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: September 24, 2009
• First Submitted That Met QC Criteria: September 24, 2009
• First Posted (Estimate): September 25, 2009

Study Record Updates

• Last Update Posted (Estimate): September 7, 2015
• Last Update Submitted That Met QC Criteria: August 7, 2015
• Last Verified: August 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; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Ribavirin
• Other Study ID Numbers: 1220.40; 2009-012579-90 (EudraCT Number: EudraCT)