Safety and efficacy of libevitug in patients with chronic hepatitis B and D virus coinfection: A single-center, open-label, phase IIa trial in China.

BACKGROUND

Chronic HBV and HDV coinfection represents the most severe form of viral hepatitis. This study aimed to assess the safety and efficacy of libevitug (HH-003), a novel human monoclonal antibody targeting the PreS1 domain of the HBV large envelope protein, in patients with chronic HBV and HDV coinfection.

METHODS

This single-center, open-label, proof-of-concept phase IIa clinical trial enrolled 9 participants who received i.v. infusion of 20 mg/kg libevitug every 2 weeks for 24 weeks, followed by a 24-week follow-up period.

RESULTS

At week 24, 8 participants (88.9%) exhibited a reduction in HDV RNA ≥1 log10 from baseline, with 4 (44.4%) achieving undetectable levels. 7 participants (77.8%) achieved virological response (undetectable HDV RNA or ≥2 log10 decline from baseline). Among the 5 participants with elevated baseline ALT, 3 (60.0%) achieved a combined virological and biochemical response (ALT normalization). At week 48, 6 participants (66.7%) maintained the virological response achieved at the end of treatment (week 24), with 3 (33.3%) maintaining undetectable HDV RNA levels. Among the 7 participants with quantifiable HBV DNA at baseline, 2 (28.6%) achieved undetectable HBV DNA or ≥1 log10 reduction at week 24. Serum HBsAg levels remained unchanged throughout the study period. Treatment-emergent adverse events were reported in 8 participants (88.9%), with only 1 participant (11.1%) experiencing treatment-related adverse events. No grade 3 or serious adverse events were reported, and no discontinuations due to adverse events occurred.

CONCLUSIONS

Libevitug demonstrated promising antiviral activity, achieving substantial HDV RNA reduction, a high rate of ALT normalization, and favorable safety and tolerability in participants with chronic HBV and HDV coinfection.