Safety and HBsAg reduction with a lentiviral vaccine J-51 in chronic hepatitis B: An investigator-initiated pilot trial.

This first-in-human, investigator-initiated trial evaluated the novel non-integrating lentiviral-vector-based therapeutic vaccine J-51 for chronic hepatitis B. The open-label pilot study enrolled seven HBeAg-negative patients with HBsAg <5,000 IU/mL. Participants received varying doses (5.0 × 107 TU-2.0 × 109 TU) in sequential cohorts to assess safety and preliminary efficacy. J-51 demonstrated a favorable safety profile across all doses, with no serious adverse events reported; all adverse events were mild and self-limiting. Preliminary efficacy in the per-protocol set (n = 6) showed that three patients (50%) achieved a >0.5 log10 IU/mL HBsAg reduction from baseline. Notably, one patient in the 1.0 × 109 TU cohort achieved HBsAg seroclearance by week 52. Responders were characterized by low baseline HBsAg levels (<120 IU/mL). These results indicate that J-51 is well tolerated and exhibits potential early biological activity, supporting a subsequent clinical trial with a larger sample size, randomized controlled design, and longer follow-up to properly evaluate its therapeutical potential.