Safety, Tolerability, Pharmacokinetics and Antiviral Activity of IONIS-HBVRx in Treatment-Naïve Patients With Chronic HBV Infection
Condition: Hepatitis B; Chronic Hepatitis B Atypical
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: IONIS-HBVRx; Placebo
Intervention description: Ascending multiple doses of IONIS-HBVRx by subcutaneous (SC) injection; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Hepatitis; Chronic; HBV

Summary:

      To examine the safety and tolerability of IONIS-HBVRx administration to treatment-naive
      patients with chronic hepatitis B virus infection
    

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])