Study of Daclatasvir (BMS-790052) and Simeprevir (TMC435) in Patients With Genotype 1 Chronic Hepatitis C Virus
Condition: Hepatitis C Virus
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: Daclatasvir; Simeprevir; Ribavirin
Intervention description: Tablets, oral, 30 mg, once daily; Capsule, oral, 150 mg, once daily; Tablets, oral, 500-600 mg, twice daily
Intervention MeSH terms: Ribavirin; Simeprevir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 230.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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