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A Safety Study of Inactivated EV71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults, Children and Infants

Primary Purpose

Hand, Foot and Mouth Disease

Status

Completed

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

160Eu/0.5ml in adults

320Eu/0.5ml in adults

640Eu/0.5ml in adults

1280Eu/0.5ml (without adjuvant) in 12 adults

0Eu/0.5ml in adults

160Eu/0.5ml in children

320Eu/0.5ml in children

640Eu/0.5ml in children

1280Eu/0.5ml (without adjuvant) in children

0Eu/0.5ml in children

160Eu/0.5ml in infants

320Eu/0.5ml in infants

640Eu/0.5ml in infants

1280Eu/0.5ml (without adjuvant) in infants

0Eu/0.5ml in infants

About this trial

This is an interventional prevention trial for Hand, Foot and Mouth Disease focused on measuring Human Enterovirus 71 (EV71), Hand, Foot and Mouth Disease, Inactivated Vaccine, Human Diploid cell, Safety, Immunogenicity, Adverse reactions associated with vaccine

Eligibility Criteria

6 Months - 49 Years (Child, Adult)All SexesAccepts Healthy Volunteers

For the subjects aged from 18-49 years old adults:

Inclusion Criteria:

Healthy subjects (18-49 years old adults) as established by medical history and clinical examination
The subjects oneself or their legal guardian must be aware of this vaccines
Voluntarily participate in the study and signed Informed Consent Form
Subjects with temperature ≤ 37.0℃
With the ability and objective to comply with the requirements of the protocol
Persist for a 2-month visit and receive blood tests according to program requirements

Exclusion Criteria:

Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
Allergy or serious side-effects to a vaccine or any ingredient of vaccine
Epilepsy, seizures, convulsions, neurological illness
Congenital or hereditary immunodeficiency
Autoimmune disease
Severe malnutrition or dysgenopathy
Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer
Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy
Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder
Acute illness or acute exacerbation of chronic disease in last 7 days
Any prior administration of immunodepressant or corticosteroids in last 6 months
Any prior administration of blood products in last 3 months
Any prior administration of live-attenuated vaccine in last 28 days or 1 months
Any prior administration of subunit or inactivated vaccines in last 14 days
Under the anti-TB prevention or therapy
Fever before vaccination, axillary temperature ﹥37.0℃
The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc.
Hypertension or hypotension. Systolic blood pressure ﹥140mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90mmHg and/or diastolic blood pressure ﹤60mmHg
Breast-feeding, pregnant, planning a pregnancy within 60 days or positive pregnancy test women
Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

For the subjects aged from 3-11 years old children:

Inclusion Criteria:

Healthy subjects (3-11 years old children) as established by medical history and clinical examination
Full-term (37-42 weeks), weight ≥ 2500 g when it was born
The subjects' legal guardian must be aware of this vaccines
The subjects' legal guardian voluntarily participate in the study and signed Informed Consent Form
Subjects with temperature ≤ 37.0℃
The subjects' legal guardian with the ability and objective to comply with the requirements of the protocol
Persist for a 2-month visit and receive blood tests according to program requirements

Exclusion Criteria:

Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
≤37 weeks gestation
weight ≤ 2500 g when it was born
Allergy or serious side-effects to a vaccine or any ingredient of vaccine
Epilepsy, seizures, convulsions, neurological illness
Congenital or hereditary immunodeficiency
Autoimmune disease
Severe malnutrition or dysgenopathy
Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer
Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy
Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder
Acute illness or acute exacerbation of chronic disease in last 7 days
Any prior administration of immunodepressant or corticosteroids in last 6 months
Any prior administration of blood products in last 3 months
Any prior administration of live-attenuated vaccine in last 28 days or 1 months
Any prior administration of subunit or inactivated vaccines in last 14 days
Under the anti-TB prevention or therapy
Fever before vaccination, axillary temperature ﹥37.0℃
The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc.
Hypertension or hypotension. Systolic blood pressure ﹥140mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90mmHg and/or diastolic blood pressure ﹤60mmHg
Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

For the subjects aged from 6-35 months infants:

Inclusion Criteria:

Healthy subjects (6-35 months infants) as established by medical history and clinical examination
Full-term (37-42 weeks), weight ≥ 2500 g when it was born
The subjects' legal guardian must be aware of this vaccines
The subjects' legal guardian voluntarily participate in the study and signed Informed Consent Form
Subjects with temperature ≤ 37.0℃
The subjects' legal guardian with the ability and objective to comply with the requirements of the protocol
Persist for a 2-month visit and receive blood tests according to program requirements

Exclusion Criteria:

Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD)
≤37 weeks gestation
weight ≤ 2500 g when it was born
Allergy or serious side-effects to a vaccine or any ingredient of vaccine
Epilepsy, seizures, convulsions, neurological illness
Congenital or hereditary immunodeficiency
Autoimmune disease
Severe malnutrition or dysgenopathy
Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer
Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy
Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder
Acute illness or acute exacerbation of chronic disease in last 7 days
Any prior administration of immunodepressant or corticosteroids in last 6 months
Any prior administration of blood products in last 3 months
Any prior administration of live-attenuated vaccine in last 28 days or 1 months
Any prior administration of subunit or inactivated vaccines in last 14 days
Under the anti-TB prevention or therapy
Fever before vaccination, axillary temperature ﹥37.0℃
The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc.
Hypertension or hypotension. Systolic blood pressure ﹥140mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90mmHg and/or diastolic blood pressure ﹤60mmHg
Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Sites / Locations

Guangxi Provincial Center for Diseases Control and Prevention

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

160Eu/0.5ml in adults

320Eu/0.5ml in adults

640Eu/0.5ml in adults

1280Eu/0.5ml (without adjuvant) in adults

0Eu/0.5ml in adults

160Eu/0.5ml in children

320Eu/0.5ml in children

640Eu/0.5ml in children

1280Eu/0.5ml (without adjuvant) in children

0Eu/0.5ml in children

160Eu/0.5ml in infants

320Eu/0.5ml in infants

640Eu/0.5ml in infants

1280Eu/0.5ml (without adjuvant) in infants

0Eu/0.5ml in infants

Arm Description

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 adults aged 18-49 years old on day 0, 14.

0Eu/0.5ml placebo in 24 adults aged 18-49 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 children aged 3-11 years old on day 0, 14.

0Eu/0.5ml placebo in 24 children aged 3-11 years old on day 0, 14.

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 24 infants aged 6-35 months old on day 0, 28.

0Eu/0.5ml placebo in 48 infants aged 6-35 months old on day 0, 28.

Outcomes

Primary Outcome Measures

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults.

Adverse reactions associated with vaccine were observed in Chinese Adults (from 18 to 49 years old) after the first vaccination.

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults.

Adverse reactions associated with vaccine were observed in Chinese Adults (from 18 to 49 years old) after the second vaccination.

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Children.

Adverse reactions associated with vaccine were observed in Chinese Children (from 3 to 11 years old) after the first vaccination.

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Children.

Adverse reactions associated with vaccine were observed in Chinese Children (from 3 to 11 years old) after the second vaccination.

Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants.

Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 35 months old) after the first vaccination.

Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants.

Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 35 months old) after the second vaccination.

Secondary Outcome Measures

Evaluate the seroconversion rate of anti-EV71 antibodies in serum of adults, children and infant, after first vaccination.

The seroconversion rate of anti-EV71 antibodies was evaluated in serum of adults within the first 14 days after first vaccination. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children within the first 14 days after first vaccination. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of infant, within the first 28 days after first vaccination.

Evaluate the seroconversion rate of anti-EV71 antibodies in serum of adults, children and infant, after second vaccination.

The seroconversion rate of anti-EV71 antibodies was evaluated in serum of adults within the first 4 days after second vaccination. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of children within the first 4 days after second vaccination. The seroconversion rate of anti-EV71 antibodies was evaluated in serum of infant, within the first 28 days after second vaccination.

Evaluate the seroconversion rate of antinuclear antibodies in serum of adults, children and infant, after first vaccination.

The seroconversion rate of antinuclear antibodies was evaluated in serum of adults within the first 14 days after first vaccination. The seroconversion rate of antinuclear antibodies was evaluated in serum of children within the first 14 days after first vaccination. The seroconversion rate of antinuclear antibodies was evaluated in serum of infant, within the first 28 days after first vaccination.

Evaluate the seroconversion rate of antinuclear antibodies in serum of adults, children and infant, after second vaccination.

The seroconversion rate of antinuclear antibodies was evaluated in serum of adults within the first 4 days after the second vaccination. The seroconversion rate of antinuclear antibodies was evaluated in serum of children within the first 4 days after the second vaccination. The seroconversion rate of antinuclear antibodies was evaluated in serum of infant, within the first 28 days after the second vaccination.

Evaluate the abnormity change of live and kidney function indexes in serum of adults, children and infant, after first vaccination.

The abnormity change of live and kidney function indexes were evaluated in serum of adults within the first 14 days after first vaccination. The abnormity change of live and kidney function indexes were evaluated in serum of children within the first 14 days after first vaccination. The abnormity change of live and kidney function indexes were evaluated in serum of infant, within the first 28 days after first vaccination.

Evaluate the abnormity change of live and kidney function indexes in serum of adults, children and infant, after second vaccination.

The abnormity change of live and kidney function indexes were evaluated in serum of adults within the first 4 days after the second vaccination. The abnormity change of live and kidney function indexes were evaluated in serum of children within the first 4 days after the second vaccination. The abnormity change of live and kidney function indexes were evaluated in serum of infant, within the first 28 days after the second vaccination.

Evaluate the vaccine-induced cellular immune responses in infant after first vaccination.

The vaccine-induced cellular immune responses were evaluated in serum of infant, within the first 28 days after the first vaccination.

Evaluate the vaccine-induced cellular immune responses in infant after second vaccination.

The vaccine-induced cellular immune responses were evaluated in serum of infant, within the first 28 days after the second vaccination.

Full Information

NCT ID

NCT01391494

First Posted

July 11, 2011

Last Updated

October 7, 2023

Sponsor

Institute of Medical Biology, Chinese Academy of Medical Sciences

Collaborators

Guangxi Center for Disease Control and Prevention

1. Study Identification

Unique Protocol Identification Number

NCT01391494

Brief Title

A Safety Study of Inactivated EV71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults, Children and Infants

Official Title

A Phase I Clinical Trial for Inactivated Enterovirus Type 71 Vaccine (Human Diploid Cell, KMB-17 Cell) in Chinese Adults, Children and Infants

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Completed

Study Start Date

February 2011 (undefined)

Primary Completion Date

June 2011 (Actual)

Study Completion Date

June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institute of Medical Biology, Chinese Academy of Medical Sciences

Collaborators

Guangxi Center for Disease Control and Prevention

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Enterovirus 71 (EV71), a major pathogen that is responsible for causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. Since the late 1990s, a series of large HFMD epidemics caused by EV71 have been reported in the Asia-Pacific region. Notably, there is evidence that the most severe cases from these epidemic outbreaks are associated with neurological disorders with CNS involvement caused by EV71 infection. Because of these EV71 infection-related public health issues, the research and development of EV71 vaccine candidates have been heavily promoted. Recently, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, including inactivated vaccine, attenuated vaccine, subunit vaccine, DNA vaccine, epitope peptide vaccine, virus-like particles (VLPs). Basing on the previous studies of elicited protection in mice and rhesus monkeys, a formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been licensed by SFDA in China, Dec. 2010. The phase I clinical trial has been carried out, during four months, in Guangxi Province, China. The purpose of this study is to evaluate the safety, tolerability and immunogenicity of the formalin-inactivated EV71 vaccine in Chinese adults (from 18 to 49 years old), children (from 3 to 11 years old) and infants (from 6 to 35 months old).

Detailed Description

Hand-foot-and-mouth disease (HFMD) is a significant cause of death, usually characterized by vesicular lesions on the skin and oral mucosa and high morbidity rates in children. Additionally, occasional fatal cases have been reported involving brainstem encephalitis and myelitis associated with cardiopulmonary collapse. Pulmonary edema/hemorrhage and respiratory failure are the major causes of death among children less than five years old. Enterovirus 71 (EV71), a major pathogen that is responsible for causing HFMD worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. Since the late 1990s, a series of large HFMD epidemics caused by EV71 have been reported in the Asia-Pacific region. Notably, there is evidence that the most severe cases from these epidemic outbreaks are associated with neurological disorders with CNS involvement caused by EV71 infection. Because of these EV71 infection-related public health issues, the research and development of EV71 vaccine candidates have been heavily promoted. Recently, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, including heat-inactivated or formalin-inactivated vaccine, live-attenuated vaccine, recombinant viral protein 1 (VP1) vaccine, VP1 DNA vaccine, VP1 epitope peptide vaccine, EV71 virus-like particles (VLPs) and bacterial or viral vector expressing VP1. Overall, the inactivated whole-virus vaccines seem to be more immunogenic than recombinant VP1 and DNA vaccines. Basing on the previous studies of elicited protection in mice and rhesus monkeys (Ying Zhang, et al. Pathogenesis study of Enterovirus 71 Infection in Rhesus Monkeys. Lab Invest, 2011, doi:10.1038/labinest.2011.82; Longding Liu, et al. Neonatal Rhesus Monkey is a Potential Animal Model for Studying Pathogenesis of EV71 Infection. Virology, 2011, 412:91-100; Chenghong Dong, et al. Immunoprotection Elicited by an Enterovirus Type 71 Experimental Inactivated Vaccine in Mice and Rhesus Monkeys. Vaccine, 2011, doi: 10.1016/j.vaccine.2011.06.044.), a formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been licensed by SFDA in China, Dec. 2010. The phase I clinical trial has been carried out, during four months, in Guangxi Province, China. The purpose of this study is to evaluate the safety, tolerability and immunogenicity of the formalin-inactivated EV71 vaccine in Chinese adults (from 18 to 49 years old), children (from 3 to 11 years old) and infants (from 6 to 35 months old).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hand, Foot and Mouth Disease

Keywords

Human Enterovirus 71 (EV71), Hand, Foot and Mouth Disease, Inactivated Vaccine, Human Diploid cell, Safety, Immunogenicity, Adverse reactions associated with vaccine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

288 (Actual)

8. Arms, Groups, and Interventions

Arm Title

160Eu/0.5ml in adults

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

Arm Title

320Eu/0.5ml in adults

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

Arm Title

640Eu/0.5ml in adults

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

Arm Title

1280Eu/0.5ml (without adjuvant) in adults

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 adults aged 18-49 years old on day 0, 14.

Arm Title

0Eu/0.5ml in adults

Arm Type

Placebo Comparator

Arm Description

0Eu/0.5ml placebo in 24 adults aged 18-49 years old on day 0, 14.

Arm Title

160Eu/0.5ml in children

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

Arm Title

320Eu/0.5ml in children

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

Arm Title

640Eu/0.5ml in children

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

Arm Title

1280Eu/0.5ml (without adjuvant) in children

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 children aged 3-11 years old on day 0, 14.

Arm Title

0Eu/0.5ml in children

Arm Type

Placebo Comparator

Arm Description

0Eu/0.5ml placebo in 24 children aged 3-11 years old on day 0, 14.

Arm Title

160Eu/0.5ml in infants

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

Arm Title

320Eu/0.5ml in infants

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

Arm Title

640Eu/0.5ml in infants

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

Arm Title

1280Eu/0.5ml (without adjuvant) in infants

Arm Type

Experimental

Arm Description

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 24 infants aged 6-35 months old on day 0, 28.

Arm Title

0Eu/0.5ml in infants

Arm Type

Placebo Comparator

Arm Description

0Eu/0.5ml placebo in 48 infants aged 6-35 months old on day 0, 28.

Intervention Type

Biological

Intervention Name(s)

160Eu/0.5ml in adults

Intervention Description

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

320Eu/0.5ml in adults

Intervention Description

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

640Eu/0.5ml in adults

Intervention Description

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 adults aged 18-49 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

1280Eu/0.5ml (without adjuvant) in 12 adults

Intervention Description

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 adults aged 18-49 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

0Eu/0.5ml in adults

Intervention Description

0Eu/0.5ml placebo in 24 adults aged 18-49 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

160Eu/0.5ml in children

Intervention Description

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

320Eu/0.5ml in children

Intervention Description

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

640Eu/0.5ml in children

Intervention Description

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 12 children aged 3-11 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

1280Eu/0.5ml (without adjuvant) in children

Intervention Description

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 12 children aged 3-11 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

0Eu/0.5ml in children

Intervention Description

0Eu/0.5ml placebo in 24 children aged 3-11 years old on day 0, 14.

Intervention Type

Biological

Intervention Name(s)

160Eu/0.5ml in infants

Intervention Description

inactivated EV71 vaccine (KMB-17) of 160Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

Intervention Type

Biological

Intervention Name(s)

320Eu/0.5ml in infants

Intervention Description

inactivated EV71 vaccine (KMB-17) of 320Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

Intervention Type

Biological

Intervention Name(s)

640Eu/0.5ml in infants

Intervention Description

inactivated EV71 vaccine (KMB-17) of 640Eu/0.5ml in 24 infants aged 6-35 months old on day 0, 28.

Intervention Type

Biological

Intervention Name(s)

1280Eu/0.5ml (without adjuvant) in infants

Intervention Description

inactivated EV71 vaccine (KMB-17) of 1280Eu/0.5ml (without adjuvant) in 24 infants aged 6-35 months old on day 0, 28.

Intervention Type

Biological

Intervention Name(s)

0Eu/0.5ml in infants

Intervention Description

0Eu/0.5ml placebo in 48 infants aged 6-35 months old on day 0, 28.

Primary Outcome Measure Information:

Title

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults.

Description

Adverse reactions associated with vaccine were observed in Chinese Adults (from 18 to 49 years old) after the first vaccination.

Time Frame

within the first 14 days after the first vaccination

Title

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults.

Description

Adverse reactions associated with vaccine were observed in Chinese Adults (from 18 to 49 years old) after the second vaccination.

Time Frame

within the first 4 days after the second vaccination

Title

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Children.

Description

Adverse reactions associated with vaccine were observed in Chinese Children (from 3 to 11 years old) after the first vaccination.

Time Frame

within the first 14 days after the first vaccination

Title

Evaluate the Safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Children.

Description

Adverse reactions associated with vaccine were observed in Chinese Children (from 3 to 11 years old) after the second vaccination.

Time Frame

within the first 4 days after the second vaccination

Title

Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants.

Description

Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 35 months old) after the first vaccination.

Time Frame

within the first 28 days after the first vaccination

Title

Evaluate the safety of Inactivated EV 71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Infants.

Description

Adverse reactions associated with vaccine were observed in Chinese Infants (from 6 to 35 months old) after the second vaccination.

Time Frame

within the first 28 days after the second vaccination

Secondary Outcome Measure Information:

Title

Evaluate the seroconversion rate of anti-EV71 antibodies in serum of adults, children and infant, after first vaccination.

Description

Time Frame

within the first 14 or 28 days after the first vaccination

Title

Evaluate the seroconversion rate of anti-EV71 antibodies in serum of adults, children and infant, after second vaccination.

Description

Time Frame

within the first 4 or 28 days after the second vaccination

Title

Evaluate the seroconversion rate of antinuclear antibodies in serum of adults, children and infant, after first vaccination.

Description

Time Frame

within the first 14 or 28 days after the first vaccination

Title

Evaluate the seroconversion rate of antinuclear antibodies in serum of adults, children and infant, after second vaccination.

Description

Time Frame

within the first 4 or 28 days after the second vaccination

Title

Evaluate the abnormity change of live and kidney function indexes in serum of adults, children and infant, after first vaccination.

Description

Time Frame

within the first 14 or 28 days after the first vaccination

Title

Evaluate the abnormity change of live and kidney function indexes in serum of adults, children and infant, after second vaccination.

Description

Time Frame

within the first 4 or 28 days after the second vaccination

Title

Evaluate the vaccine-induced cellular immune responses in infant after first vaccination.

Description

The vaccine-induced cellular immune responses were evaluated in serum of infant, within the first 28 days after the first vaccination.

Time Frame

within the first 28 days after the first vaccination

Title

Evaluate the vaccine-induced cellular immune responses in infant after second vaccination.

Description

The vaccine-induced cellular immune responses were evaluated in serum of infant, within the first 28 days after the second vaccination.

Time Frame

within the first 28 days after the second vaccination

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

49 Years

Accepts Healthy Volunteers

Eligibility Criteria

For the subjects aged from 18-49 years old adults: Inclusion Criteria: Healthy subjects (18-49 years old adults) as established by medical history and clinical examination The subjects oneself or their legal guardian must be aware of this vaccines Voluntarily participate in the study and signed Informed Consent Form Subjects with temperature ≤ 37.0℃ With the ability and objective to comply with the requirements of the protocol Persist for a 2-month visit and receive blood tests according to program requirements Exclusion Criteria: Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD) Allergy or serious side-effects to a vaccine or any ingredient of vaccine Epilepsy, seizures, convulsions, neurological illness Congenital or hereditary immunodeficiency Autoimmune disease Severe malnutrition or dysgenopathy Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder Acute illness or acute exacerbation of chronic disease in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6 months Any prior administration of blood products in last 3 months Any prior administration of live-attenuated vaccine in last 28 days or 1 months Any prior administration of subunit or inactivated vaccines in last 14 days Under the anti-TB prevention or therapy Fever before vaccination, axillary temperature ﹥37.0℃ The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc. Hypertension or hypotension. Systolic blood pressure ﹥140mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90mmHg and/or diastolic blood pressure ﹤60mmHg Breast-feeding, pregnant, planning a pregnancy within 60 days or positive pregnancy test women Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives For the subjects aged from 3-11 years old children: Inclusion Criteria: Healthy subjects (3-11 years old children) as established by medical history and clinical examination Full-term (37-42 weeks), weight ≥ 2500 g when it was born The subjects' legal guardian must be aware of this vaccines The subjects' legal guardian voluntarily participate in the study and signed Informed Consent Form Subjects with temperature ≤ 37.0℃ The subjects' legal guardian with the ability and objective to comply with the requirements of the protocol Persist for a 2-month visit and receive blood tests according to program requirements Exclusion Criteria: Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD) ≤37 weeks gestation weight ≤ 2500 g when it was born Allergy or serious side-effects to a vaccine or any ingredient of vaccine Epilepsy, seizures, convulsions, neurological illness Congenital or hereditary immunodeficiency Autoimmune disease Severe malnutrition or dysgenopathy Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder Acute illness or acute exacerbation of chronic disease in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6 months Any prior administration of blood products in last 3 months Any prior administration of live-attenuated vaccine in last 28 days or 1 months Any prior administration of subunit or inactivated vaccines in last 14 days Under the anti-TB prevention or therapy Fever before vaccination, axillary temperature ﹥37.0℃ The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc. Hypertension or hypotension. Systolic blood pressure ﹥140mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90mmHg and/or diastolic blood pressure ﹤60mmHg Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives For the subjects aged from 6-35 months infants: Inclusion Criteria: Healthy subjects (6-35 months infants) as established by medical history and clinical examination Full-term (37-42 weeks), weight ≥ 2500 g when it was born The subjects' legal guardian must be aware of this vaccines The subjects' legal guardian voluntarily participate in the study and signed Informed Consent Form Subjects with temperature ≤ 37.0℃ The subjects' legal guardian with the ability and objective to comply with the requirements of the protocol Persist for a 2-month visit and receive blood tests according to program requirements Exclusion Criteria: Subject who has a clinical diagnosis history of Hand, Foot and Mouth Disease (HFMD) ≤37 weeks gestation weight ≤ 2500 g when it was born Allergy or serious side-effects to a vaccine or any ingredient of vaccine Epilepsy, seizures, convulsions, neurological illness Congenital or hereditary immunodeficiency Autoimmune disease Severe malnutrition or dysgenopathy Asthma, thyroidectomy, angioneurotic edema, diabetes or cancer Asplenia, functional asplenia, and any circumstances leading to the asplenia or splenectomy Clinical diagnosis of coagulopathy (such as clotting factor deficiency, coagulation disorders, platelet abnormalities), significant bruising or blood clotting disorder Acute illness or acute exacerbation of chronic disease in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6 months Any prior administration of blood products in last 3 months Any prior administration of live-attenuated vaccine in last 28 days or 1 months Any prior administration of subunit or inactivated vaccines in last 14 days Under the anti-TB prevention or therapy Fever before vaccination, axillary temperature ﹥37.0℃ The laboratory test abnormalities before vaccination, including blood tests (hemoglobin, total white blood cells, WBC, platelets), blood biochemistry tests (ALT, total bilirubin, direct bilirubin, Cr, BUN) and urine tests (urine protein, urine sugar, blood cells), etc. Hypertension or hypotension. Systolic blood pressure ﹥140mmHg and/or diastolic blood pressure ﹥90mmHg; systolic blood pressure ﹤90mmHg and/or diastolic blood pressure ﹤60mmHg Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zhaojun Mo, Master

Organizational Affiliation

Guangxi Provincial Center for Diseases Control and Prevention

Official's Role

Principal Investigator

Facility Information:

Facility Name

Guangxi Provincial Center for Diseases Control and Prevention

City

Nanning

State/Province

Guangxi

ZIP/Postal Code

530028

Country

China

12. IPD Sharing Statement

Citations:

PubMed Identifier

23372725

Citation

Liu L, Zhang Y, Wang J, Zhao H, Jiang L, Che Y, Shi H, Li R, Mo Z, Huang T, Liang Z, Mao Q, Wang L, Dong C, Liao Y, Guo L, Yang E, Pu J, Yue L, Zhou Z, Li Q. Study of the integrated immune response induced by an inactivated EV71 vaccine. PLoS One. 2013;8(1):e54451. doi: 10.1371/journal.pone.0054451. Epub 2013 Jan 23.

Results Reference

derived

Links:

URL

http://www.nature.com/labinvest/journal/vaop/ncurrent/abs/labinvest201182a.html

Description

The rhesus monkey model may be used to study not only the basic pathogenesis of EV71 viral infections, but also to examine clinical features, such as neurological lesions, in the CNS and pathological changes in associated organs.

Learn more about this trial

A Safety Study of Inactivated EV71 Vaccine (Human Diploid Cell, KMB-17) in Chinese Adults, Children and Infants

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