safety, tolerability, pharmacokinetics and antiviral activity of ionis-hbvrx in treatment-naïve patients with chronic hbv infection

Conditions: Hepatitis B; Chronic Hepatitis B Atypical

Summary: to examine the safety and tolerability of ionis-hbvrx administration to treatment-naive patients with chronic hepatitis b virus infection

this study examines the effects of ionis-hbvrx or placebo (3:1 randomization) administered subcutaneously to treatment-naïve patients who are chronically infected with hbv and the effects of subsequent nucleos(t)ide analogue treatment on these patients.

Eligibility criteria:
inclusion criteria: * age 18 to 70 years * chronic hbv infection ≥6 months (e.g., positive for serum hbsag ≥ 6 months) * plasma hbv dna ≥ 2 x 1000 iu/ml (hbv dna adequately suppressed for exploratory nucleos(t)ide analogue experienced cohort) * serum hbsag ≥ 50 iu/ml * exploratory nucleos(t)ide analogue experienced cohort only: currently taking and have been taking tenofovir or entecavir without changes in drug, dose level and/or frequency of administration for ≥ 12 months and expect to continue taking without change through to the end of their participation in this study 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 \[pcp\])

Keywords: hepatitis chronic hbv