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

H. Pylori Infection Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02302170
• Other study ID #: TMMUHP03
• Status: Completed
• Phase: Phase 3
• First received: November 24, 2014
• Last updated: November 25, 2014
• Start date: December 2004
• Est. completion date: September 2008

Study information

• Verified date: November 2014
• Source: Jiangsu Province Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4464
• Est. completion date: September 2008
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 15 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• H. Pylori Infection
• Helicobacter Infections

Intervention

Biological:
• H. pylori vaccine

• placebo

Locations

Country	Name	City	State
China	Jiangsu Provincial Center for Diseases Control and Prevention	Nanjing	Jiangsu

Sponsors (4)

Lead Sponsor	Collaborator
Jiangsu Province Centers for Disease Control and Prevention	Kangwei biological technology Co., Ltd (renamed as Wuhu Kangwei biological technology Co., Ltd. in 2011), National Institute of Food and Drug Control, Third Military Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The occurrence of Helicobacter pylori infection in participants one year after three-dose vaccinations.		one year after the third dose	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	The occurrence of Helicobacter pylori infection in participants in the second year after three-dose vaccinations.		in the second year after the third dose	No
Secondary	The occurrence of Helicobacter pylori infection in participants in the third year after three-dose vaccinations.		in the third year after the third dose.	No