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.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Biological: H.pylori vaccines; Biological: Placebo Vaccine

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Magdeburg, Germany, 39120
    • Otto Von Guericke Universität Magdeburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: 2	Biological: Placebo Vaccine; Placebo Vaccine at 0, 1, and 2 months
EXPERIMENTAL: 1	Biological: H.pylori vaccines; 1 dose of H.pylori vaccine at 0, 1, and 2 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to 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).	12 weeks post HP challenge
Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination	To assess the tolerability of an HP vaccine versus placebo in terms of number of subjects reporting solicited local* and systemic adverse events.	Day 1-7 post vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups	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.	12 months
The Geometric Mean Concentrations After HP Vaccination.	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.	upto 1 month after 3rd vaccination
Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge.	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.	12 months
Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge	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.	12 weeks post HP challenge
Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI)	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.	12 weeks post HP challenge

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): March 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: August 13, 2008
• First Submitted That Met QC Criteria: August 13, 2008
• First Posted (ESTIMATE): August 15, 2008

Study Record Updates

• Last Update Posted (ACTUAL): February 28, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: vaccination; adults; helicobacter pylori infection
• Additional Relevant MeSH Terms: Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Helicobacter Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V99P2; 2007-003511-31