Efficacy and Safety of an H.Pylori Vaccine in H.Pylori-Negative Adults

Phase I/II, Randomized, Observer-blind, Placebo-controlled, Single-Center Study of the Tolerability, Immunogenicity, and Efficacy of an Novartis' Investigational H. Pylori Vaccine in H. Pylori-Negative Adults

To study the safety, immunogenicity and efficacy of an investigational H. pylori vaccine, compared with placebo.

The efficacy of the investigational vaccine to prevent infection following H.pylori challenge in healthy adults was determined in terms of percentage of subjects with positive HP infections in the vaccinated and unvaccinated groups(Placebo). Infection rates was assessed by invasive Upper Gastrointestinal Endoscopy (UGE)tests that included HP histopathology, HP culture and rapid urease test (RUT), and non-invasive HP tests which included urea breath test (UBT) and fecal antigen test (FAT).

To assess the tolerability of an HP vaccine versus placebo in terms of number of subjects reporting solicited local* and systemic adverse events.

The time course of HP infection following HP challenge in subjects of the HP vaccine and placebo groups, were assessed by non-invasive HP tests.

The geometric mean concentration of IgG antibody responses to each of the HP vaccine antigens (VacA, CagA and NAP)after HP vaccination as compared to placebo are reported.

The geometric mean concentration of IgG antibody responses to each of the HP vaccine antigens (VacA, CagA and NAP) after HP challenge were compared between vaccinated and placebo groups.

The response to 3 doses of HP vaccine and the oral HP challenge was assessed with respect their ability to induce differentiation and changes in the phenotype of a subset of regulatory T-cells CD4+CD25+Foxp3+ that expresses Treg Markers PD-1 and/or HLA-DR.

The proliferation of H. pylori-specific Peripheral blood mononuclear cells (PBMCs) following HP antigen stimulation was assessed to measure the magnitude of the cell mediated immune response.

Inclusion Criteria: adults 18 - 40 years of age in good health HP uninfected not pregnant and agree to use birth control throughout the study (females who can become pregnant) Exclusion Criteria: remote or current HP infection

Malfertheiner P, Selgrad M, Wex T, Romi B, Borgogni E, Spensieri F, Zedda L, Ruggiero P, Pancotto L, Censini S, Palla E, Kanesa-Thasan N, Scharschmidt B, Rappuoli R, Graham DY, Schiavetti F, Del Giudice G. Efficacy, immunogenicity, and safety of a parenteral vaccine against Helicobacter pylori in healthy volunteers challenged with a Cag-positive strain: a randomised, placebo-controlled phase 1/2 study. Lancet Gastroenterol Hepatol. 2018 Oct;3(10):698-707. doi: 10.1016/S2468-1253(18)30125-0. Epub 2018 Jul 2.

Nell S, Estibariz I, Krebes J, Bunk B, Graham DY, Overmann J, Song Y, Sproer C, Yang I, Wex T, Korlach J, Malfertheiner P, Suerbaum S. Genome and Methylome Variation in Helicobacter pylori With a cag Pathogenicity Island During Early Stages of Human Infection. Gastroenterology. 2018 Feb;154(3):612-623.e7. doi: 10.1053/j.gastro.2017.10.014. Epub 2017 Oct 21.