Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection
Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants With Chronic Hepatitis C Virus Genotype 1 Infection
The purpose of this study is to evaluate the efficacy of 6 or 8 weeks of treatment regimen
 containing simeprevir (SMV), daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive (not
 having received treatment with any approved or investigational drug) participants with
 chronic hepatitis (inflammation of the liver) C virus (HCV) genotype 1 infection with early
 stages of liver fibrosis or with cirrhosis.
This is an open-label (participants and researchers are aware about the treatment
 participants are receiving), and multicenter (when more than 1 hospital or medical school
 team work on a medical research) study. The study will consist of a Screening Phase (6
 weeks); an Open-label Treatment Phase (6 weeks for Arm A and 8 weeks for Arm B); and a
 Post-treatment Follow-up Phase (until 24 weeks after end of study treatment). Using a
 staggered approach, all eligible participants will be assigned to 1 of the 2 arms, according
 to their level of fibrosis. Arm A (consists of chronic HCV genotype 1 infected participants
 with early stages of liver fibrosis): participants will receive a combination therapy of SMV
 150 milligram (mg), DCV 60 mg and SOF 400 mg once daily for 6 weeks. Arm B (consists of
 chronic HCV genotype 1 infected participants with cirrhosis): participants will receive a
 combination therapy of SMV 150 mg, DCV 60 mg and SOF 400 mg once daily for 8 weeks. A
 sub-study will be performed at a selected study site, where only participants who will be
 eligible to participate in both the main study and the sub-study will be enrolled.
 Intra-hepatic and plasma HCV ribonucleic acid (RNA) levels; intra-hepatic, peripheral innate
 and adaptive immune responses during the treatment, will be assessed in the sub-study.
 Participants' safety will be monitored throughout the study.
Inclusion Criteria:

 -  HCV genotype 1 infection and HCV RNA plasma level greater than (>) 10,000
 international units per milliliter (IU/mL), both determined at Screening

 -  Participants of Arm A should have evidence of early stages of liver fibrosis, defined
 by a FibroSURE score less than or equal to (<=) 0.48 and aspartate aminotransferase to
 platelet ratio index (APRI) score <=1

 -  Participants of Arm B should have evidence of cirrhosis, defined by a FibroSURE score
 >0.75 and APRI score >2, OR a previous (historical) biopsy documenting a METAVIR score
 F4. In addition, participants should have absence of esophageal varices or presence of
 small (grade 1) esophageal varices determined by upper gastrointestinal endoscopy, and
 absence of findings indicative of hepatocellular carcinoma in an ultrasonography

 -  HCV treatment-naive, defined as not having received treatment with any approved or
 investigational drug for chronic HCV infection

 -  Pegylated interferon (PegIFN) and ribavirin (RBV) eligible, defined as not having any
 contraindication to the use of PegIFN and RBV, in line with the prescribing
 information for each compound

 Exclusion Criteria:

 A. Main Study:

 -  Co-infection with HCV of another genotype than genotype 1 and/or human
 immunodeficiency virus (HIV) type 1 or 2 (positive HIV-1 or HIV 2 antibody test at
 Screening)

 -  Any evidence of liver disease of non-HCV etiology. This includes, but is not limited
 to, acute hepatitis A infection, hepatitis B infection (hepatitis B surface antigen
 positive), drug- or alcohol-related liver disease, autoimmune hepatitis,
 hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, non-alcoholic
 steatohepatitis, primary biliary cirrhosis, or any other non-HCV liver disease
 considered clinically significant by the Investigator

 -  Evidence of clinical hepatic decompensation or presence of grade 2/3 esophageal
 varices

 -  Any of the protocol defined laboratory abnormalities

 B. Sub-study:

 -  Presence of coagulopathy (hemophilia) or hemoglobinopathy (including sickle cell
 disease, thalassemia)

 -  Use of any anti-coagulant (for example, warfarin, heparin) or anti-platelet
 medications within 1 week of the Screening visit

 -  Any of the protocol defined laboratory abnormalities