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)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: PegIFN/RBV; BI 201335; BI 201335; Placebo
Intervention description: PegIFN/RBV for 48 weeks; BI 201335 once daily high dose; BI 201335 once daily low dose
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 656.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion criteria:

          1. Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detected
             HCV RNA at screening in addition to:

               1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to
                  screening; or,

               2. liver biopsy consistent with chronic HCV infection.

          2. HCV genotype 1 infection confirmed by genotypic testing at screening.

          3. Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral /
             immunomodulatory drug for acute or chronic HCV infection.

          4. HCV RNA = 1,000 IU/mL at screening

          5. 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.

          6. Age 18 to 70 years

          7. Female patients:

               1. with documented hysterectomy,

               2. who have had both ovaries removed,

               3. with documented tubal ligation,

               4. who are post-menopausal with last menstrual period at least 12 months prior to
                  screening, or

               5. 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:

               1. who are documented to be sterile, or

               2. 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).

          8. Signed informed consent form prior to 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. Incidental steatosis diagnosed by biopsy is not an exclusion criterion.

          3. HIV co-infection

          4. Hepatitis B virus (HBV) infection based on presence of HBs-Ag

          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 other than cannabis 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 patients 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 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.

         10. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days
             prior to randomization and throughout the treatment phase of this trial.

         11. Known hypersensitivity to any ingredient of the study drugs.

         12. 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.