Controlled Interruption of Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Infections

Prior treatment

• Planned or recent (<6 months before inclusion) participation in other therapeutic interventional trials
• Ever receiving a HBV small interfering RNA (siRNA) investigational medicinal product

Other illness

• Active confection: hepatitis C virus (HCV) RNA positive, hepatitis delta virus (HDV) RNA positive, human immunodeficiency virus (HIV) antigen (Ag)-Antibody (Ab) positive
• Patients with a family history of HCC despite compliance to standard of care follow-up

Lab values

• INR >1.3xULN (ULN = 1.1) (unless casued by anticoagulation therapy or vitamin K deficiency) at any point prior to or at the time of screening
• Total bilirubin >1.2xULN (ULN = 1.2 mg/dL) (unless there is documentation of a benign cause such as Gilbert's disease) at any point prior to or at the time of screening
• Last Fibroscan result >9kPa and/or last ShearWave elastography (SWE) result >8.15 kPa. EASL clinical practice guidelines on non-invasive tests for liver fibrosis should be applied to determine the correctness and reliability of the elastography result, considering a max interquartile range/median of 30% and max ALT of 5xULN at elastography evaluation.
• Extrahepatic manifestations of chronic hepatitis B. This includes: polyarteritis nodosa, glomerulonephritis, serum sickness-like prodrome, essential mixed cryoglobulinemia, dermatologic manifestations, arthritic manifestations and neurologic manifestations.

Other

• Pregancy or lactation
• Fibrosis >= F3 in most recent biopsy
• Immunocompromised individuals (for definitions cfr. Study Protocol or the National Health Service (NHS) criteria)
• Patients that have either an antecedent of or ongoing HCC

• >= 18 years old <= 75 years old
• Chronic hepatitis B, defined as HBsAg positive or HBV DNA positive >= 6 months
• Start of NA-treatment HBeAg negative
• Under continuous NA treatment
• HBV DNA below the local limit of quantification for at least 36 months at cessatino or <= 2log IU/mL for at least 48 months at cessation
• ALT <= 2x Upper Limit Normal (40 U/L) on 2 sequential measurements at least 6 months apart (one of which is at screening)