Safety and immunogenicity of the therapeutic vaccine TG1050 in chronic hepatitis B patients: a phase 1b placebo-controlled trial

• Main Authors: Fabien Zoulim (Author), Claire Fournier (Author), François Habersetzer (Author), Martin Sprinzl (Author), Stanislas Pol (Author), Carla S Coffin (Author), Vincent Leroy (Author), Mang Ma (Author), Heiner Wedemeyer (Author), Ansgar W Lohse (Author), Robert Thimme (Author), Karine Lugardon (Author), Perrine Martin (Author), Bérangère Bastien (Author), Benoit Sansas (Author), Nathalie Adda (Author), Celine Halluard (Author), Kaïdre Bendjama (Author), Maud Brandely (Author), Geneviève Inchauspé (Author)
• Format: Book
• Published: Taylor & Francis Group, 2020-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2164-5515; 2164-554X; 10.1080/21645515.2019.1651141
• Keywords: hepatitis b; chronicity; immuno-therapy; vaccine; safety; immunogenicity; Immunologic diseases. Allergy; RC581-607; Therapeutics. Pharmacology; RM1-950
• Source: Human Vaccines & Immunotherapeutics, Vol 16, Iss 2, Pp 388-399 (2020)

Treatment of chronic hepatitis B (CHB) typically requires life-long administration of drugs. Cohort and pre-clinical studies have established the link between a functional T-cell-mounted immunity and resolution of infection. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and surface antigen and has shown immunogenicity and antiviral effects in mice. We performed a phase 1 clinical trial to assess safety and explore immunogenicity and early efficacy of TG1050 in CHB patients. This randomized, double blind, placebo-controlled study included two sequential phases: one single dose cohort (SD, n = 12) and one multiple (3) doses cohort (MD, n = 36). Patients, virally suppressed under nucleoside(d)tide analog NUC therapy, were randomized 1:1:1 across 3 dose levels (DL) and assigned to receive 109, 1010, 1011 virus particles (vp) of TG1050 and then randomized within each DL to placebo (3:1 and 9:3 vaccines/placebo in each DL, respectively, for the SD and MD cohorts). Cellular (ELISPOT) and antibody responses (anti-Adenovirus), as well as evolution of circulating HBsAg and HBcrAg, were monitored. All doses were well tolerated in both cohorts, without severe adverse event. TG1050 was capable to induce IFN-γ producing T-cells targeting 1 to 3 encoded antigens, in particular at the 1010vp dose. Overall, minor decreases of HBsAg were observed while a number of vaccinees reached unquantifiable HBcrAg by end of the study. In CHB patients under NUC, TG1050 exhibited a good safety profile and was capable to induce HBV-specific cellular immune response. These data support further clinical evaluation, especially in combination studies.