Subcutaneous RBD4059 safely suppresses FXI activity in healthy volunteers for up to 6 months.

This Phase 1 randomized controlled trial evaluated the safety and tolerability of subcutaneous RBD4059, an N-acetylgalactosamine-conjugated small interfering RNA targeting factor XI (FXI), in a population of six healthy volunteers. The intervention was compared against placebo, with follow-up extending to day 169, or approximately 6.0 months. The study design allowed for the assessment of both primary safety outcomes and secondary pharmacokinetic and pharmacodynamic parameters.

The primary outcome measured FXI activity suppression, which demonstrated a dose-dependent and durable effect exceeding 90% in the treatment groups. Secondary outcomes included the evaluation of pharmacokinetic and pharmacodynamic parameters, though specific numerical data for these metrics were not reported in the provided evidence. No adverse events, serious adverse events, or discontinuations were reported during the study period.

Tolerability was characterized as well tolerated, with no apparent safety concerns identified across the observation window. The study limitations are not explicitly detailed in the available data, and funding or conflict of interest information was not reported. Consequently, the certainty of these findings is constrained by the small sample size and early-phase nature of the trial.

The practice relevance of this evidence supports the continued clinical development of RBD4059. This siRNA-based therapeutic option targets FXI and may offer a solution for patients who are inadequately treated with or contraindicated for currently available thrombosis prophylaxis options. Further research is required to confirm efficacy and safety in broader patient populations.