Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ-73763989 in Healthy Chinese Adult Participants.

Abstract

JNJ-73763989, composed of the 2 short-interfering RNA triggers JNJ-73763976 and JNJ-73763924, targets all hepatitis B virus messenger RNAs, thereby reducing all viral proteins. In this phase 1, single-site, open-label, parallel-group, randomized study, participants were given 1 subcutaneous injection of JNJ-73763989 (100 or 200mg) to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Chinese adult participants. Plasma and urine pharmacokinetic parameters were determined for each trigger up to 48hours after dosing. Eighteen participants, 9 per dose group, were enrolled. The median age and weight were 33.0 years and 73.65kg; 83.3% were male. Exposure of both triggers increased dose proportionally. Median time to maximum concentration ranged from 6.0 to 10.0hours, and mean elimination half-life ranged from 4.5 to 4.8hours across both triggers and doses. Mean urinary excretion for JNJ-73763976 and JNJ-73763924 ranged from 17.7% to 19.4% and 13.1% to 13.2% for the 100- and 200-mg dose groups, respectively. All treatment-emergent adverse events (AEs) were mild and resolved by study end, and no AEs or serious AEs resulted in premature study discontinuation or death. Overall, the pharmacokinetics of JNJ-73763989 in healthy Chinese participants were consistent with previous studies, and JNJ-73763989 was generally safe and well tolerated after a single dose.