A Single Ascending Dose Study of Single-Stranded Oligodeoxyribonucleotide RO7062931 in Chinese Healthy Volunteers.

RO7062931 is an N-acetylgalactosamine (GalNAc)-conjugated single-stranded oligodeoxyribonucleotide complementary to hepatitis B virus (HBV) RNA. GalNAc conjugation targets the liver through the asialoglycoprotein receptor (ASGPR). This phase I single ascending dose (SAD) study evaluated the safety, tolerability and pharmacokinetics of RO7062931 in Chinese healthy volunteers. There were 4 SAD cohorts (0.3, 1.0, 2.0, and 4.0 mg/kg), in each of which healthy volunteers were randomized to a single subcutaneous (SC) injection of RO7062931 or matching placebo in a 4:1 ratio. Placebo recipients were pooled as one treatment group for safety assessments. A total of 41 healthy Chinese men received one dose of RO7062931 (n=33) or placebo (n=8) and completed the study (85-day follow-up). Adverse events (AEs) were reported in 22 of 33 (66.6%) RO7062931 recipients (n=8 treatment-related) and 7 of 8 (87.5%) placebo recipients (n=1 treatment-related). Apart from two moderate-intensity AEs, all AEs were mild. The most frequently reported AEs were influenza, injection-related reactions and headache. Dose-proportional increases in plasma RO7062931 exposure were observed between the 0.3 and 1.0 mg/kg doses, whereas a supra-dose-proportional increase occurred at doses ≥ 2.0 mg/kg, along with a marked increase in urinary excretion. Single SC dose of RO7062931 up to 4.0 mg/kg were safe and well tolerated in healthy Chinese volunteers. PK data suggested that ASGPR saturation had commenced between doses of 2.0 mg/kg and 4.0 mg/kg. Results were broadly consistent with observations in primarily white subjects in the global first in-human study of RO7062931.