IFN-free Combination Therapy in HCV-infected Patients Treatment-naive:HCVerso1

A Phase III, Randomized, Partially Double-Blind and Placebo-Controlled Study of BI 207127 in Combination With Faldaprevir and Ribavirin in Treatment-Naive Patients With Chronic Genotype 1 HCV Infection

The aim of the study is to confirm efficacy of treatment for 16 and 24 weeks in chronically infected HCV GT1b treatment naïve patients, including patients with compensated cirrhosis.

Inclusion criteria:

• Chronic hepatitis C infection, diagnosed by positive HCV Ab or detectable HCV RNA at screening in addition to at least one of the following:

  1. positive HCV RNA or HCV antibodies at least 6 months prior to screening, or
  2. liver biopsy typical of chronic hepatitis C , or
  3. history of elevated ALT at least 6 months prior to screening.

• HCV infection of sub-GT1b confirmed by genotypic testing at screening

• Treatment naïve defined as:

  1. no prior treatment with any interferon, pegylated interferon, and /or ribavirin and
  2. no prior treatment with at least one dose of any other licensed or investigational antiviral agent for acute or chronic hepatitis C infection

• Plasma HCV RNA > or = 1,000 IU/mL at screening

• Liver biopsy within three years or fibroscan within six months prior to randomization. Patients with compensated liver cirrhosis (score Child-Pugh A) could also be included.

• Age 18 to 75 years

• Female patients with a negative urine pregnancy test (dipstick) at Visit 2 prior to randomization

  1. with documented hysterectomy, or
  2. who have had both ovaries removed, or
  3. with documented tubal ligation, or
  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 a negative urine pregnancy test on Day 1 (Visit 2), that agree to use two non-hormonal methods of birth control from the date of screening until months after the last dose of ribavirin. They must not 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 diaphragm with spermicide substance, intrauterine devices, cervical caps and condoms.

OR:

Male patients

1. who are documented to be sterile, or
2. who consistently and correctly use a condom while their female partners (if of child-bearing potential) 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, and
3. without pregnant female partners. It is in the responsibility of the male patient to ensure that his partner (or partners) is not pregnant prior to enrolment into the study or becomes pregnant during the treatment and follow-up phase. Female partners of childbearing potential must 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).

Exclusion criteria:

• HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening.
• HCV subtype 1a, mixed 1a/1b or GT1 undefined
• Evidence of liver disease mainly due to causes other than chronic HCV infection such as autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis or Wilson's disease
• HIV-1 or HIV-2 infection
• Hepatitis B virus (HBV) infection based on presence of HBs-Ag
• Evidence of decompensated liver disease, or history of decompensated liver disease, defined as history of ascites, hepatic encephalopathy, or bleeding esophageal varices,
• International Normalized Ratio (INR) > or =1.7
• Serum albumin < 3.3 g/dL
• Serum total bilirubin >2.0 times the upper limit of normal (ULN) with direct/indirect ratio >1, unless history of Gilbert's disease
• Active or suspected malignancy or history of malignancy within the last 5 years (with the exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix)
• Patients with ongoing or historical photosensitivity or recurrent rash