Safety and immunogenicity of the therapeutic vaccine TG1050 in chronic hepatitis B patients: a phase 1b placebo-controlled trial
| Title: | Safety and immunogenicity of the therapeutic vaccine TG1050 in chronic hepatitis B patients: a phase 1b placebo-controlled trial |
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| Authors: | 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 |
| Source: | Human Vaccines & Immunotherapeutics, Vol 16, Iss 2, Pp 388-399 (2020) |
| Publisher Information: | Taylor & Francis Group, 2020. |
| Publication Year: | 2020 |
| Collection: | LCC:Immunologic diseases. Allergy LCC:Therapeutics. Pharmacology |
| Subject Terms: | hepatitis b, chronicity, immuno-therapy, vaccine, safety, immunogenicity, Immunologic diseases. Allergy, RC581-607, Therapeutics. Pharmacology, RM1-950 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2164-5515 2164-554X 21645515 |
| Relation: | https://doaj.org/toc/2164-5515; https://doaj.org/toc/2164-554X |
| DOI: | 10.1080/21645515.2019.1651141 |
| Access URL: | https://doaj.org/article/c456bcbade694a3c9f70d46d5542f9b0 |
| Accession Number: | edsdoj.456bcbade694a3c9f70d46d5542f9b0 |
| Database: | Directory of Open Access Journals |
| ISSN: | 21645515 2164554X |
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| DOI: | 10.1080/21645515.2019.1651141 |
| Published in: | Human Vaccines & Immunotherapeutics |
| Language: | English |