A Phase Ⅲ Clinical Trial With Oral Recombinant Helicobacter Pylori Vaccine in Chinese Children

Study Overview
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Brief Summary
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Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium that persistently colonizes the human stomach; more than half the human population is infected worldwide. H. pylori infection is a risk factor for the development of gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The phaseⅠand Ⅱclinical trial of oral recombinant Helicobacter pylori vaccine had completed in Jiangsu Province in China. The data from phaseⅠand Ⅱclinical trial suggested that the oral recombinant Helicobacter pylori vaccine had a clinically acceptable safety and good immunogenicity for health adults and children. To further explore the safety and immunogenicity profile of this vaccine, a phase Ⅲ clinical trial was conducted.

Detailed Description
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Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium that persistently colonizes the human stomach; more than half the human population is infected worldwide. H. pylori infection is the major risk factor for the development of gastritis, peptic ulcer, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. At present, the main clinical treatment for H. pylori infection is the application of antibiotics and bismuth agent or H+ antagonists. Due to the widespread drug resistance, toxic side effects, high medical costs as well as poor patient compliance, it is unworkable to practice antibiotics therapy for H. pylori eradication on every patient. Vaccination is the most effective way for prevention H. pylori infection. Since H. pylori were found, great attention has been given to the H. pylori vaccine, scientists worldwide have made great efforts to develop both prophylactic and therapeutic H. pylori vaccine. Numerous H. pylori vaccine approaches have been studied, including inactivated whole cell H. pylori vaccine, genetic engineering subunit vaccine, live vector vaccines. Urease is considered to be an excellent candidate antigen for vaccine against H. pylori. However, no vaccine against H. pylori has been used in clinic. The phaseⅠand Ⅱclinical trial of oral recombinant Helicobacter pylori vaccine had completed in Jiangsu Province in China. The data from phaseⅠand Ⅱclinical trial suggested that the oral recombinant Helicobacter pylori vaccine had a clinically acceptable safety and good immunogenicity for children. To further explore the safety and immunogenicity profile of this vaccine, a phase Ⅲ clinical trial was conducted.

Official Title
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A Phase Ⅲ Clinical Trial for Efficacy, Immunogenicity, Safety and Immune Persistence of Oral Recombinant Helicobacter Pylori Vaccine in Chinese Children Aged From 6-15 Years Old.

Conditions
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H. Pylori Infection

Intervention / Treatment
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* Biological: H. pylori vaccine
* Biological: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children aged from 6-15 years old as established by medical history and clinical examination The subjects' guardians are able to understand and sign the informed consent Subjects who can and will comply with the requirements of the protocol Subjects with temperature <=37.0°C on axillary setting before vaccination Exclusion Criteria: Exclusion criteria for the first dose Subject who has a medical history of stomach illness Positive in either serology ELISA test for Helicobacter pylori diagnose kit or 13C urea breath test Subject who has suffered from heart, liver, and kidney disease Subject who has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine (for example: mannitol) Subject who is suffering from thrombocytopenia or other coagulation disorder Subject who has a diminished function of the immune system or autoimmune disease Subject who is suffering from congenital deformities, developmental disorders or serious chronic diseases Family history of seizures or progressive neurological disease Severe malnutrition or dysgenopathy, major congenital defects or serious chronic illness, including perinatal brain damage Any acute infections in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6 month Any prior administration of other research medicines in last 1 month Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion criteria for the second and third dose Subjects will not be eligible for the second or third dose if any of following happened after first dose Subject who had allergic reaction to the last dose Any situation meet the exclusion criteria occurred after the last dose Subject who had any serious adverse events related to the vaccination Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: H. pylori vaccine in children<br>H. pylori vaccine (15mg/dose) in children between 6-15 years of age | Biological: H. pylori vaccine<br> <br> * Other names: Oral Recombinant Helicobacter Pylori Vaccine;|
| Placebo Comparator: placebo in children<br>placebo (0mg/dose) in children between 6-15 years of age | Biological: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of Helicobacter pylori infection in participants one year after three-dose vaccinations. |  | one year after the third dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The immune response of anti-UreB IgG antibodies in serum after three-dose vaccinations in the immunogenicity subset of participants | seroconversion rates, GMTs, GMFI of anti-UreB IgG antibodies in serum after three-dose vaccinations in the immunogenicity subset of participants at month 1. | 1 month after the third dose | 
| The immune response of anti-UreB sIgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants | conversion rates, GMTs, GMFI of anti-UreB sIgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants at month 1 | 1 month after the third dose | 
| The immune response of anti-UreB IgG antibodies in serum three-dose vaccinations in the immunogenicity subset of participants. | seroconversion rates, GMTs, GMFI of anti-UreB IgG antibodies in serum after three-dose vaccinations in the immunogenicity subset of participants at month 6 | 6 months after the third dose | 
| The immune response of anti-UreB IgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants | To evaluate conversion rates, GMTs, GMFI of anti-UreB sIgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants at month 6 | 6 months after the third dose | 
| The immune response of anti-UreB IgG antibodies in serum after three-dose vaccinations in the immunogenicity subset of participants | seroconversion rates, GMTs, GMFI of anti-UreB IgG antibodies in serum after three-dose vaccinations in the immunogenicity subset of participants at month 12 | 12 months after the third dose | 
| The immune response of anti-UreB sIgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants | conversion rates, GMTs, GMFI of anti-UreB sIgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants at month 12 | 12 months after the third dose | 
| Frequency of adverse reactions after taking the H. pylori vaccines in children | Frequency of adverse reactions within 3 days after taking the H. pylori vaccines in children | within 3 days after each vaccination | 
| Occurrence of serious adverse reactions after taking the H. pylori vaccines in children | Occurrence of serious adverse reactions within one year after the third dose in children | From day 0 to One year after the third dose | 
| Anti-UreB IgG antibodies persistency in serum after three-dose vaccinations in the immunogenicity subset of participants | seroconversion rates, GMTs, GMFI of anti-UreB IgG antibodies in serum after three-dose vaccinations in the immunogenicity subset of participants at month 24 | 24 months after the third dose | 
| Anti-UreB IgA antibodies persistency in saliva after three-dose vaccinations in the immunogenicity subset of participants | conversion rates, GMTs, GMFI of anti-UreB sIgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants at month 24 | 24 months after the third dose | 
| Anti-UreB IgG antibodies persistency in serum after three-dose vaccinations in the immunogenicity subset of participants | seroconversion rates, GMTs, GMFI of anti-UreB IgG antibodies in serum after three-dose vaccinations in the immunogenicity subset of participants at month 36 | 36 months after the third dose | 
| Anti-UreB IgA antibodies persistency in saliva after three-dose vaccinations in the immunogenicity subset of participants | To evaluate conversion rates, GMTs, GMFI of anti-UreB sIgA antibodies in saliva after three-dose vaccinations in the immunogenicity subset of participants at month 36 | 36 months after the third dose | 
| The occurrence of Helicobacter pylori infection in participants in the second year after three-dose vaccinations. |  | in the second year after the third dose | 
| The occurrence of Helicobacter pylori infection in participants in the third year after three-dose vaccinations. |  | in the third year after the third dose. |