Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection.

ABSTRACT: Poly(A) RNA polymerases D5 and D7 (PAPD5, PAPD7) are host factors that stabilize hepatitis B virus (HBV) RNA transcripts. RO7239958, a liver-targeted locked nucleic acid (LNA) antisense oligonucleotide (ASO), induces intracellular degradation of PAPD5- and PAPD7-encoding messenger RNAs (mRNAs). This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of RO7239958 in healthy volunteers and adults with chronic hepatitis B (CHB) receiving standard-of-care antiviral therapy. Forty healthy volunteers were randomized (4:1) to single ascending subcutaneous doses of RO7239958 (0.1, 0.3, 1.0, or 1.5 mg/kg) or placebo. Based on a population PK model built to predict liver exposure, two parallel CHB cohorts (n = 8 and n = 7 per cohort) we

SUBMITTER: Geretti AM 

PROVIDER: S-EPMC12691668 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature