New Treatment Response in People With and Without Cirrhosis From Chronic Hepatitis C

Inclusion criteria

-INCLUSION CRITERIA: INCLUSION CRITERIA FOR BOTH GENOTYPES 1a and 1b: 1. Adults, ages 18 and above 2. Chronic hepatitis C (HCV RNA in serum for more than 6 months) 3. HCV Genotype 1 4. HCV RNA in serum above 10,000 IU/mL 5. Non-response to previous therapy with peginterferon and ribavirin categorized as null-response as defined by a less than 1 log IU/mL decline in HCV RNA at treatment week 4 or a less than 2 log IU/mL decline in HCV RNA at treatment week 12; and partial response as defined by a greater than or equal to 2 log decrease in HCV RNA at treatment week 12 but continued detection of HCV RNA at treatment week 24 6. No contraindications to agents being used (asunaprevir, daclatasvir, peginterferon and ribavirin). 7. No evidence or history of hepatic decompensation. 8. Females of childbearing potential must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug. 9. Women of childbearing potential (WOCBP) and men must use highly effective methods of birth control to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of P/R. Birth control requirements are or WOCBP and men who are sexually active with WOCBP 10. Women must not be breastfeeding 11. Fully informed, written consent to the study including repeat liver biopsy. ADDITIONAL INCLUSION CRITERIA FOR GENOTYPE 1a 1\) Liver biopsy showing Ishak stages 0-2 or 5-6 within 12 weeks of initiating therapy OR a prior biopsy performed within 96 weeks of screening visit WITH saved tissue. Up to 10 subjects who do not fulfill the entry histologic criteria will be allowed to participate in the trial at the discretion of the investigator. ADDITIONAL INCLUSION CRITERIA FOR GENOTYPE 1b 1. Baseline sequence analysis of the NS5A region to exclude presence of mutations known to confer resistance to daclatasvir. INCLUSION CRITERIA FOR GT 1b SUBJECTS WHO RECEIVE RESCUE THERAPY AT THE DISCREATION OF THE INVESTIGATOR (THESE CRITERIA MUST BE ASSESSED PRIOR TO INITIATIONOF PEG INFa/RBV THERAPY): Important: In addition to the Inclusion Criteria listed above, the following Inclusion Criteria apply to all Rescue Subjects: a) Subject met a definition of virologic breakthrough or treatment futility, defined as: i) Any confirmed \> 1 log10 increase in HCV RNA from nadir, OR; ii) Any confirmed HCV RNA greater than or equal to Lower Limit of quantification (LLOQ) after confirmed HCV RNA \<LLOQ Target Not Detected while on treatment, OR; iii) Any confirmed HCV RNA greater than or equal to LLOQ at Week 8. Measurements should be confirmed within 2 weeks of the Week 8 result; b) HCV RNA \< 400,000 IU/mL at the last assessment; This cut-off was chosen because it is felt that peginterferon and ribavirin would be ineffective at higher viral loads in prior non-responders to peginterferon and ribavirin with viral breakthrough. c) Women of childbearing potential (WOCBP)1 and men must use highly effective methods of birth control to minimize the risk of pregnancy. WOCBP must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of P/R. Birth control requirements are or WOCBP (see Section C.5 for the definition of WOCBP) and men who are sexually active with WOCBP; i) Two (2) forms of birth control are required from time of screening throughout the duration of the on-treatment study period and for at least 24 weeks after the last dose of RBV (or the duration specified by the country-specific RBV label, whichever is longer), in such a manner that the risk of pregnancy is minimized. Examples of highly effective birth control include: -condom with spermicide; -diaphragm and spermacide; -cervical cap and spermacide * female condom; * intrauterine devices (IUDs); Oral contraceptive pills (OCPs) may be used in this study but cannot be considered as an effective form of contraception for WOCBP subjects. ii) Exceptions include: 1. WOCBP who are not heterosexually active or who have male partners who have been vasectomized for a minimum of 6 months with a history of confirmed azoospermia; 2. Sexually active men who are vasectomized for a minimum of 6 months with a history of confirmed azoospermia. d) WOCBP must have a negative serum or urine pregnancy test \[minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)\] within 24 hours prior to the start of P/R. Female subjects must agree to the pregnancy testing requirements of this protocol; e) Women must not be breastfeeding; f) Male Subjects: Requirements (based on RBV label): i) Male subjects (unless vasectomized for at least 6 months with a history of confirmed azoospermia) with female partners who are WOCBP must agree to inform their female partners of the protocol-specified effective birth control methods requirement and pregnancy testing recommendations during treatment and post-treatment (i.e., two forms of effective methods of birth control and monthly pregnancy testing while the subject is enrolled in the study and 6 months following discontinuation of RBV \[or for the post-treatment duration specified in the country-specific RBV label\]), and agree to adhere to these recommendations both on-treatment and during the post-treatment follow-up period; ii) Male subjects must confirm that their female sexual partners are not pregnant at the time of screening.