Helicobacter Pylori Infection
Conditions
Keywords
helicobacter pylori infection, vaccination, adults
Brief summary
To study the safety, immunogenicity and efficacy of an investigational H. pylori vaccine, compared with placebo.
Interventions
BIOLOGICALH.pylori vaccines
1 dose of H.pylori vaccine at 0, 1, and 2 months
BIOLOGICALPlacebo Vaccine
Placebo Vaccine at 0, 1, and 2 months
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | 12 weeks post HP challenge | 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). |
| Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Day 1-7 post vaccination | To assess the tolerability of an HP vaccine versus placebo in terms of number of subjects reporting solicited local\* and systemic adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 months | 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 Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 12 months | 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. |
| Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | 12 weeks post HP challenge | 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. |
| Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 12 weeks post 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. |
| The Geometric Mean Concentrations After HP Vaccination. | upto 1 month after 3rd 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. |
Countries
Germany
Participant flow
Recruitment details
Subjects were recruited from a single study center in Germany
Pre-assignment details
All subjects enrolled were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| Group I (HP Vaccine) Subjects received three injections of HP Vaccine at 0, 1, and 2 months. | 36 |
| Group II (Placebo) Subjects received three injections of Placebo at 0, 1, and 2 months | 27 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Group I (HP Vaccine) | Group II (Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 5.7 | 24.0 years STANDARD_DEVIATION 3.3 | 26.1 years STANDARD_DEVIATION 5.1 |
| Gender Female | 16 Participants | 17 Participants | 33 Participants |
| Gender Male | 20 Participants | 10 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 36 | 25 / 27 |
| serious Total, serious adverse events | 1 / 36 | 0 / 27 |
Outcome results
Primary
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.
Time frame: Day 1-7 post vaccination
Population: This analysis was done on the safety dataset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site erythema* | 14 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Myalgia | 17 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site warmth* | 4 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Arthralgia | 4 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Any Local* | 28 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Headache | 13 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site tenderness* | 23 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Fatigue | 13 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site induration* | 8 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Rash | 2 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site pain* | 24 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Fever (≥38C) | 0 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Chills | 2 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Any Other# | 2 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Any Systemic | 26 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Analgesic antipyretic medication used# | 9 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site swelling* | 5 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Stayed at home due to reaction# | 2 Participants |
| Group I (HP Vaccine) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Malaise | 4 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Stayed at home due to reaction# | 0 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Any Local* | 23 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site erythema* | 7 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site induration* | 5 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site swelling* | 2 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site warmth* | 3 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site tenderness* | 20 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Injection site pain* | 14 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Chills | 0 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Malaise | 3 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Myalgia | 11 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Arthralgia | 1 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Headache | 10 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Fatigue | 7 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Rash | 0 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Fever (≥38C) | 0 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Any Other# | 2 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Analgesic antipyretic medication used# | 4 Participants |
| Group II (Placebo) | Number of Subjects Reporting Solicited Local* and Systemic Adverse Events Following Vaccination | Any Systemic | 18 Participants |
Primary
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).
Time frame: 12 weeks post HP challenge
Population: Per-protocol dataset
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I (HP Vaccine) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | UBT positive (non-invasive test) | 0 Percentage of subjects |
| Group I (HP Vaccine) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | FAT positive (non-invasive test) | 21 Percentage of subjects |
| Group I (HP Vaccine) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | HP culture positive (invasive test) | 36 Percentage of subjects |
| Group I (HP Vaccine) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | RUT positive (invasive test) | 7 Percentage of subjects |
| Group I (HP Vaccine) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | Histopathology positive (invasive test) | 7 Percentage of subjects |
| Group I (HP Vaccine) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | Positive HP infection (Invasive+non-invasive) | 36 Percentage of subjects |
| Group II (Placebo) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | Histopathology positive (invasive test) | 0 Percentage of subjects |
| Group II (Placebo) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | UBT positive (non-invasive test) | 0 Percentage of subjects |
| Group II (Placebo) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | RUT positive (invasive test) | 0 Percentage of subjects |
| Group II (Placebo) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | FAT positive (non-invasive test) | 8 Percentage of subjects |
| Group II (Placebo) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | Positive HP infection (Invasive+non-invasive) | 46 Percentage of subjects |
| Group II (Placebo) | The Efficacy (Defined as Prevention of Infection) of the HP Vaccine Compared to Placebo. | HP culture positive (invasive test) | 46 Percentage of subjects |
Secondary
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.
Time frame: 12 months
Population: Per-protocol dataset
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (CagA) | 149 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (VacA) | 117 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (CagA ) | 13 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (VacA) | 21 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (VacA) | 565 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (CagA) | 30 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (CagA) | 16 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 month after 1st vaccination (NAP) | 101 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (NAP) | 125 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 month after 1st vaccination (NAP) | 117 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (VacA) | 606 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (NAP) | 115 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (CagA) | 2.25 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (VacA) | 2174 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination(CagA ) | 2.24 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (NAP) | 19 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (CagA ) | 2.39 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (VacA) | 3467 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (NAP) | 179 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (NAP) | 4.4 μg/mL |
| Group I (HP Vaccine) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (VacA) | 1219 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (VacA) | 1943 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination(CagA ) | 4.54 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (VacA) | 285 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (VacA) | 2754 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (VacA) | 912 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (VacA) | 1469 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (CagA ) | 14 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (CagA ) | 93 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (CagA) | 134 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (CagA) | 261 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (CagA) | 202 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (VacA) | 979 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (NAP) | 4.4 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (NAP) | 62 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 month after 1st vaccination (NAP) | 235 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (CagA) | 2.64 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 month after 1st vaccination (NAP) | 251 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (NAP) | 275 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (NAP) | 325 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (VacA) | 24 μg/mL |
| Group II (Placebo) | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (NAP) | 208 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (NAP) | 4.4 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (VacA) | 28 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (NAP) | 5.58 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (NAP) | 5.46 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (VacA) | 24 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (VacA) | 20 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (CagA) | 4.17 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 month after 1st vaccination (NAP) | 5.54 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination(CagA ) | 3.84 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (CagA) | 3.92 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (VacA) | 25 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (VacA) | 20 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (CagA) | 4.11 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (CagA ) | 3.84 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (CagA ) | 4.08 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (VacA) | 16 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (CagA) | 7.51 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 month after 1st vaccination (NAP) | 5.35 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (VacA) | 58 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (NAP) | 4.4 μg/mL |
| Group II (Placebo) Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (NAP) | 5.46 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (VacA) | 73 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (VacA) | 33 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (VacA) | 45 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (CagA) | 3.53 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination(CagA ) | 3.06 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 months after 1st vaccination (CagA ) | 2.95 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (CagA ) | 2.63 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (CagA) | 3.59 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (CagA) | 3.39 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (CagA) | 4.73 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (NAP) | 11 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (NAP) | 8.48 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 month after 1st vaccination (NAP) | 6.61 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 2 weeks post HP challenge (NAP) | 8.3 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (NAP) | 8.32 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 12 weeks post HP challenge (NAP) | 8.01 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | Baseline (VacA) | 41 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 1 month after 1st vaccination (VacA) | 33 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 months after 1st vaccination (VacA) | 34 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 4 weeks post HP challenge (VacA) | 46 μg/mL |
| Group II (Placebo) Non-Infected | Geometric Mean Concentrations Against Vaccine Antigens After HP Challenge. | 3 month after 1st vaccination (NAP) | 6.59 μg/mL |
Secondary
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.
Time frame: 12 weeks post HP challenge
Population: Per-protocol dataset
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (HP Vaccine) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | HP challenge (N=21,16) | 26 Stimulation Index (SI) | Standard Deviation 21 |
| Group I (HP Vaccine) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | Screening | 6.85 Stimulation Index (SI) | Standard Deviation 6.05 |
| Group I (HP Vaccine) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | 2 weeks post challenge (N=17,13) | 53 Stimulation Index (SI) | Standard Deviation 37 |
| Group I (HP Vaccine) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | 12 weeks post challenge (N=13,12) | 28 Stimulation Index (SI) | Standard Deviation 23 |
| Group II (Placebo) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | 12 weeks post challenge (N=13,12) | 7.83 Stimulation Index (SI) | Standard Deviation 2.82 |
| Group II (Placebo) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | 2 weeks post challenge (N=17,13) | 24 Stimulation Index (SI) | Standard Deviation 19 |
| Group II (Placebo) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | Screening | 3.69 Stimulation Index (SI) | Standard Deviation 3.7 |
| Group II (Placebo) | Proliferative Response Against the Pooled H. Pylori Vaccine Antigens by Stimulation Index (SI) | HP challenge (N=21,16) | 3.81 Stimulation Index (SI) | Standard Deviation 2.61 |
Secondary
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.
Time frame: 12 weeks post HP challenge
Population: Per-protocol dataset
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | Screening (FOXP3+) | 1.12 percentage of T-cells | Standard Deviation 0.33 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | HP challenge (FOXP3+) (N=18,15) | 1.15 percentage of T-cells | Standard Deviation 0.43 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 2 weeks post challenge (FOXP3+) (N=15,14) | 1.34 percentage of T-cells | Standard Deviation 0.38 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 12 weeks post challenge (FOXP3+)(N=10,9) | 1.34 percentage of T-cells | Standard Deviation 0.45 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | Screening (HLADR TOT) | 24 percentage of T-cells | Standard Deviation 8.22 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | HP challenge (HLADR TOT) (N=18,15) | 23 percentage of T-cells | Standard Deviation 8.36 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 2 weeks post challenge (HLADR TOT) (N=15,14) | 23 percentage of T-cells | Standard Deviation 8.36 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 12 weeks post challenge (HLADR TOT) (N=10,9) | 21 percentage of T-cells | Standard Deviation 7.95 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | Screening (PD-1 TOT) | 5.8 percentage of T-cells | Standard Deviation 2.55 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | HP challenge (PD-1 TOT) (N=18,15) | 5.69 percentage of T-cells | Standard Deviation 1.93 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 2 weeks post challenge (PD-1 TOT) (N=15,14) | 6.12 percentage of T-cells | Standard Deviation 2.38 |
| Group I (HP Vaccine) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 12 weeks post challenge (PD-1 TOT) (N=10,9) | 4.33 percentage of T-cells | Standard Deviation 1.31 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 2 weeks post challenge (PD-1 TOT) (N=15,14) | 5.79 percentage of T-cells | Standard Deviation 2.52 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | Screening (FOXP3+) | 1.13 percentage of T-cells | Standard Deviation 0.56 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | HP challenge (FOXP3+) (N=18,15) | 1.07 percentage of T-cells | Standard Deviation 0.48 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 2 weeks post challenge (HLADR TOT) (N=15,14) | 21 percentage of T-cells | Standard Deviation 8.44 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | HP challenge (PD-1 TOT) (N=18,15) | 5.4 percentage of T-cells | Standard Deviation 2.74 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 2 weeks post challenge (FOXP3+) (N=15,14) | 1.31 percentage of T-cells | Standard Deviation 0.57 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 12 weeks post challenge (HLADR TOT) (N=10,9) | 23 percentage of T-cells | Standard Deviation 11 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 12 weeks post challenge (FOXP3+)(N=10,9) | 0.87 percentage of T-cells | Standard Deviation 0.48 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | 12 weeks post challenge (PD-1 TOT) (N=10,9) | 5.53 percentage of T-cells | Standard Deviation 2.11 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | Screening (HLADR TOT) | 22 percentage of T-cells | Standard Deviation 10 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | Screening (PD-1 TOT) | 5.22 percentage of T-cells | Standard Deviation 2.06 |
| Group II (Placebo) | Response on Activated Regulatory T Cell Subset Following HP Vaccination and HP Challenge | HP challenge (HLADR TOT) (N=18,15) | 24 percentage of T-cells | Standard Deviation 11 |
Secondary
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.
Time frame: upto 1 month after 3rd vaccination
Population: Per-Protocol dataset
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | Baseline (CagA antigen) | 2.42 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 1 month after 1st vaccination (CagA antigen) | 2.89 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 2 months after 1st vaccination (CagA antigen) | 7.74 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 3 months after 1st vaccination (CagA antigen) | 23 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | Baseline (NAP antigen) | 4.59 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 1 month after 1st vaccination (NAP antigen) | 35 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 2 months after 1st vaccination (NAP antigen) | 236 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 3 months after 1st vaccination (NAP antigen) | 148 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | Baseline (VacA antigen) | 18 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 1 month after 1st vaccination (VacA antigen) | 214 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 2 months after 1st vaccination (VacA antigen) | 2468 μg/mL |
| Group I (HP Vaccine) | The Geometric Mean Concentrations After HP Vaccination. | 3 months after 1st vaccination (VacA antigen) | 502 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 2 months after 1st vaccination (VacA antigen) | 23 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | Baseline (CagA antigen) | 2.95 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 2 months after 1st vaccination (NAP antigen) | 5.15 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 1 month after 1st vaccination (CagA antigen) | 2.55 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 1 month after 1st vaccination (VacA antigen) | 23 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 2 months after 1st vaccination (CagA antigen) | 2.56 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 3 months after 1st vaccination (NAP antigen) | 2.54 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 3 months after 1st vaccination (CagA antigen) | 2.54 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 3 months after 1st vaccination (VacA antigen) | 19 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | Baseline (NAP antigen) | 5.84 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | Baseline (VacA antigen) | 21 μg/mL |
| Group II (Placebo) | The Geometric Mean Concentrations After HP Vaccination. | 1 month after 1st vaccination (NAP antigen) | 5.47 μg/mL |
Secondary
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.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 4 weeks post challenge (UBT positive) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 1 week post challenge (FAT positive) | 9 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 8 weeks post challenge (UBT positive) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 1 week post challenge (UBT positive) | 4 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 12 weeks post challenge (UBT positive) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 3 weeks post challenge (FAT positive) | 2 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Post eradication (UBT positive) (N=7,7) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Baseline (UBT positive) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Baseline (FAT positive) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 4 weeks post challenge (FAT positive) | 3 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 2 weeks post challenge (UBT positive) | 1 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 8 weeks post challenge (FAT positive) | 3 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 2 weeks post challenge (FAT positive) | 8 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 12 weeks post challenge (FAT positive) | 3 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 3 weeks post challenge (UBT positive) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Post eradication (FAT positive) (N=7,7) | 0 Participants |
| Group I (HP Vaccine) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | HP challenge (≥3 months after vaccination) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Post eradication (FAT positive) (N=7,7) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 1 week post challenge (FAT positive) | 9 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 2 weeks post challenge (FAT positive) | 9 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Baseline (UBT positive) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | HP challenge (≥3 months after vaccination) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 1 week post challenge (UBT positive) | 1 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 3 weeks post challenge (FAT positive) | 5 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 2 weeks post challenge (UBT positive) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 3 weeks post challenge (UBT positive) | 1 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 4 weeks post challenge (UBT positive) | 1 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 8 weeks post challenge (UBT positive) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 12 weeks post challenge (UBT positive) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Post eradication (UBT positive) (N=7,7) | 0 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 4 weeks post challenge (FAT positive) | 4 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 8 weeks post challenge (FAT positive) | 4 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | 12 weeks post challenge (FAT positive) | 1 Participants |
| Group II (Placebo) | The Time Course of HP Infection Following HP Challenge in Vaccinated and Placebo Groups | Baseline (FAT positive) | 0 Participants |