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 2)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis
Intervention: BI201335; PegIFN/RBV; BI201335; Placebo
Intervention description: QD BI 201335; QD (once daily) BI 201335
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 658.0
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 of the
             screening visit.

             Note: If cirrhosis has been previously demonstrated on a biopsy, then biopsies
             obtained more than 3 years before enrolment need not be repeated. Biopsies can be
             waived for patients who would be placed at risk from the procedure. Inability to do a
             liver biopsy should not exclude patients from a trial.

          6. Age 18 to 70 years

          7. Female patients:

             (c) with documented hysterectomy, (d) who have had both ovaries removed, (e) with
             documented tubal ligation, (f) who are post-menopausal with last menstrual period at
             least 12 months prior to screening, or (g) 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.

          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.

          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 patient¿s ability to participate in this study.

          8. Usage of any investigational drugs within 28 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 28 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, or Sho-saiko-to (SST) within 28 days
             prior to screening and throughout the treatment phase.

         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).

         13. Decompensated liver disease, or history of decompensated liver disease, as defined by
             the presence of: hepatic encephalopathy, ascites, or esophageal variceal bleeding
             and/or laboratory results of any of the following:

               1. International normalized ratio (INR) of =1.7

               2. Serum Albumin =3.5 g/dL

               3. Serum total bilirubin =2.0 mg/dL (except when the increase is predominately due
                  to unconjugated bilirubin and related to Gilberts syndrome).

         14. Pre-existing psychiatric condition that could interfere with the subject¿s
             participation in and completion of the study including but not limited to prior
             suicidal attempt, schizophrenia, major depression syndrome, severe anxiety, severe
             personality disorder, a period of disability or impairment due to a psychiatric
             disease within the past 5 years.