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)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III, Randomised, Double-blind and Placebo-controlled Study of Once Daily BI 201335 120 mg for 12 or 24 Weeks or BI 201335 240 mg for 12 Weeks in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-naïve Patients With Genotype 1 Chronic Hepatitis C Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: PegIFN/RBV
* Drug: BI 201335
* Drug: BI 201335
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: 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 prior to screening; or, liver biopsy consistent with chronic HCV infection. HCV genotype 1 infection confirmed by genotypic testing at screening. Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection. HCV RNA = 1,000 IU/mL at screening 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. Age 18 to 70 years Female patients: with documented hysterectomy, who have had both ovaries removed, with documented tubal ligation, who are post-menopausal with last menstrual period at least 12 months prior to screening, or 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: who are documented to be sterile, or 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). Signed informed consent form prior to trial participation Exclusion criteria: HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening 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. HIV co-infection Hepatitis B virus (HBV) infection based on presence of HBs-Ag 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) Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months 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 Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study. 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. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to randomization and throughout the treatment phase of this trial. Known hypersensitivity to any ingredient of the study drugs. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PegIFN/RBV<br>PegIFN/RBV for 48 weeks | Drug: PegIFN/RBV<br>* PegIFN/RBV for 48 weeks<br>|
| Experimental: BI 201335 for 12 or 24 weeks<br>BI 201335 once daily low dose for 12 or 24 weeks in combination with PegIFN/RBV for 24 or 48 weeks | Drug: PegIFN/RBV<br>* PegIFN/RBV for 48 weeks<br>Drug: BI 201335<br>* BI 201335 once daily high dose<br>Drug: BI 201335<br>* BI 201335 once daily low dose<br>|
| Active Comparator: Placebo and PegIFN/RBV<br>Placebo (oral) once daily plus PegIFN/RBV (subcutaneous injection/oral) for 24 weeks, followed by PegIFN/RBV alone up to Week 48. | Drug: PegIFN/RBV<br>* PegIFN/RBV for 48 weeks<br>Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response 12 Weeks Post-treatment (SVR12) | Sustained Virological Response 12 weeks post-treatment (SVR12), defined as plasma Hepatitis C virus (HCV) Ribonucleic acid (RNA) level < 25 IU/mL (undetected) 12 weeks after the originally planned treatment duration. | 12 weeks post treatment, up to 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response 24 Weeks Post-treatment (SVR24) | Sustained Virological Response 24 weeks post-treatment (SVR24), defined as plasma HCV RNA level < 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration. | 24 weeks post treatment, up to 72 weeks | 
| Early Treatment Success (ETS) | Early treatment success (ETS), defined as a plasma HCV RNA level <25 IU/mL (detected or undetected) at week 4 and HCV RNA <25 IU/mL (undetected) at week 8. | week 4 and week 8 | 
| 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 | 12 weeks post treatment, up to 60 weeks | 
| 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 | 12 weeks post treatment, up to 60 weeks | 
| 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. BL = Baseline | 12 weeks post treatment, up to 60 weeks | 
| 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. BL = Baseline | 12 weeks post treatment, up to 60 weeks | 
| 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 | 12 weeks post treatment, up to 60 weeks | 
| 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 | 12 weeks post treatment, up to 60 weeks | 
| 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. BL = Baseline | 12 weeks post treatment, up to 60 weeks | 
| 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. BL = Baseline | 12 weeks post treatment, up to 60 weeks |