Chronic hepatitis B (CHB) treatment generally necessitates medication administration for the rest of one’s life. Cohort and pre-clinical investigations have found a connection between functional T-cell-mounted immunity and infection clearance. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase as well as core and surface antigen domains and has demonstrated immunogenicity and antiviral activity in mice. Researchers conducted a phase 1 clinical trial in CHB patients to evaluate the safety, immunogenicity, and early effectiveness of TG1050. This randomized, double-blind, placebo-controlled research was divided into two phases: one for single doses and one for multiple doses. Patients who had been virally suppressed with nucleoside(d)tide analog NUC treatment were randomized 1:1:1 across three dosage levels (DL) to receive 109, 1010, or 1011 virus particles (vp) of TG1050, and subsequently randomized to placebo within each DL. Cellular (ELISPOT) and antibody responses were tracked, as well as the development of circulating HBsAg and HBcrAg. TG1050, particularly at the 1010vp dosage, was capable of inducing IFN-producing T-cells targeting 1 to 3 encoded antigens.
Overall, modest reductions in HBsAg were seen, but a few of vaccines achieved unquantifiable HBcrAg levels by the conclusion of the trial. In CHB patients receiving NUC, TG1050 demonstrated a favorable safety profile and the ability to produce an HBV-specific cellular immune response. These findings suggest additional clinical investigation, particularly in combination trials.