Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection

Exclusion Criteria

• •Current or prior receipt of anti-HBV nucleos(t)ide analogue therapy. Patients who have failed prior interferon treatment, greater than 6 months prior to Screening, may be evaluated for possible participation in the study (not applicable for exploratory nucleos(t)ide analogue experienced cohort)
• •History of liver cirrhosis and/or evidence of cirrhosis as determined by any of the following:
• •1. Liver biopsy (i.e., Metavir Score F4) within 2 years of Screening, or
• •2. Fibroscan \> 12 KPa, within 12 months of Screening, or
• •3. AST-to-Platelet Index (APRI) \> 2 and Fibrosure result \> 0.7 within 12 months of Screening For patients without a test for cirrhosis in the above timeframes, Fibroscan, or APRI and Fibrosure, may be performed during the screening period to rule out cirrhosis
• •History of liver failure as evidenced by ascites, hepatic encephalopathy, and/or gastric or esophageal varices
• •History of liver disease other than Hepatitis B
• •Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)
• •BMI \> 35 kg/m2
• •History of, or suspected presence of vasculitis
• •Received solid organ or bone marrow transplant
• •Currently taking, or took within 3 months of Screening, any immunosuppressing drugs (e.g., prednisone)
• •Diagnosed hepatocellular carcinoma or suspected hepatocellular carcinoma as evidenced by screening alpha-fetoprotein ≥ 200 ng/mL. If the screening alpha-fetoprotein is ≥ 50 ng/mL and \< 200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization
• •Clinically-significant abnormalities aside from chronic HBV infection in medical history (e.g., previous acute coronary syndrome within 6 months of Screening, major surgery within 3 months of Screening, uncontrolled diabetes) or physical examination
• •History of bleeding diathesis or coagulopathy
• •History of extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis, polyarteritis nodosa)
• •History of excess alcohol consumption within 6 months of Screening
• •History of drug abuse or dependence, or recreational use of drugs: within 3 months of Screening for soft drugs (such as marijuana) and within 1-year of Screening for hard drugs (such as cocaine, phencyclidine \[PCP\])