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

Autor: Fabien Zoulim, Claire Fournier, François Habersetzer, Martin Sprinzl, Stanislas Pol, Carla S Coffin, Vincent Leroy, Mang Ma, Heiner Wedemeyer, Ansgar W Lohse, Robert Thimme, Karine Lugardon, Perrine Martin, Bérangère Bastien, Benoit Sansas, Nathalie Adda, Celine Halluard, Kaïdre Bendjama, Maud Brandely, Geneviève Inchauspé
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Human Vaccines & Immunotherapeutics, Vol 16, Iss 2, Pp 388-399 (2020)
Druh dokumentu: article
ISSN: 2164-5515
2164-554X
21645515
DOI: 10.1080/21645515.2019.1651141
Popis: 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.
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