Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus

A Phase 2, Open-Label Study of Daclatasvir (BMS-790052) and TMC435 in Combination With or Without Ribavirin (RBV) For Treatment-Naive Subjects or Null Responders to Prior Peginterferon Alfa (PegIFN)/RBV Therapy With Genotype 1 Chronic Hepatitis C

The purpose of this study is to assess the safety and efficacy of daclatasvir and simeprevir with and without ribavirin for genotype 1 chronic hepatitis C virus infection in patients who are treatment-naive or null responders to previous pegylated interferon/ribavirin therapy.

Key Inclusion Criteria:

• Hepatitis C virus (HCV) genotype 1a or 1b

• Males and females, ≥18 years of age

• HCV RNA ≥10,000 IU/mL

• Participants with compensated cirrhosis are permitted

  • Advanced fibrosis (F3/F4) is capped at approximately 35% of the total treated population with a minimum of 20% F4 patients
  • If no cirrhosis, a liver biopsy within 3 years prior to enrollment
  • If cirrhosis is present, any prior liver biopsy

Key Exclusion Criteria:

• Liver or any other transplant (other than cornea and hair)
• Evidence of a medical condition contributing to chronic liver disease other than HCV infection
• Current or known history of cancer, (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment
• Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
• Patients infected with HIV or hepatitis B virus
• Gastrointestinal disease impacting absorption of study drug
• Uncontrolled diabetes or hypertension
• Prior exposure to an HCV direct-acting agent
• Any criteria that would exclude the patient from receiving ribavirin
• Absolute neutrophil count <1.5*1,000,000,000 cells/L (<1.2*1,000,000,000 cells/L for Black/African Americans)
• Platelets <90*1,000,000,000 cells/L
• Hemoglobin <12 g/dL for females, <13 g/dL for males
• Alanine aminotransferase ≥5*upper limit of normal
• In patients without cirrhosis, total bilirubin ≥2 mg/dL unless patient has a documented history of Gilbert's disease
• In patients with cirrhosis, total bilirubin o ≥1.5 mg/dL
• International normalized ratio ≥1.7
• QTcF or QTcB >500 mSec
• Creatinine clearance ≤50 mL/min
• Alpha fetoprotein (AFP) >100 ng/mL OR
• AFP ≥50 ng/mL and ≤100 ng/mL requiring liver ultrasound
• Albumin <3.5 g/dL