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

NCT ID: NCT01391494

Last Updated: 2023-10-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

288 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-02-28

Study Completion Date

2011-06-30

Brief Summary

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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

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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).

Conditions

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Hand, Foot and Mouth Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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160Eu/0.5ml in adults

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

Group Type EXPERIMENTAL

160Eu/0.5ml in adults

Intervention Type BIOLOGICAL

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

320Eu/0.5ml in adults

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

Group Type EXPERIMENTAL

320Eu/0.5ml in adults

Intervention Type BIOLOGICAL

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

640Eu/0.5ml in adults

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

Group Type EXPERIMENTAL

640Eu/0.5ml in adults

Intervention Type BIOLOGICAL

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

1280Eu/0.5ml (without adjuvant) in adults

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

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

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 in adults

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

Group Type PLACEBO_COMPARATOR

0Eu/0.5ml in adults

Intervention Type BIOLOGICAL

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

160Eu/0.5ml in children

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

Group Type EXPERIMENTAL

160Eu/0.5ml in children

Intervention Type BIOLOGICAL

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

320Eu/0.5ml in children

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

Group Type EXPERIMENTAL

320Eu/0.5ml in children

Intervention Type BIOLOGICAL

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

640Eu/0.5ml in children

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

Group Type EXPERIMENTAL

640Eu/0.5ml in children

Intervention Type BIOLOGICAL

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

1280Eu/0.5ml (without adjuvant) in children

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

Group Type EXPERIMENTAL

1280Eu/0.5ml (without adjuvant) in children

Intervention Type BIOLOGICAL

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 in children

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

Group Type PLACEBO_COMPARATOR

0Eu/0.5ml in children

Intervention Type BIOLOGICAL

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

160Eu/0.5ml in infants

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

Group Type EXPERIMENTAL

160Eu/0.5ml in infants

Intervention Type BIOLOGICAL

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

320Eu/0.5ml in infants

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

Group Type EXPERIMENTAL

320Eu/0.5ml in infants

Intervention Type BIOLOGICAL

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

640Eu/0.5ml in infants

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

Group Type EXPERIMENTAL

640Eu/0.5ml in infants

Intervention Type BIOLOGICAL

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

1280Eu/0.5ml (without adjuvant) in infants

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

Group Type EXPERIMENTAL

1280Eu/0.5ml (without adjuvant) in infants

Intervention Type BIOLOGICAL

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 in infants

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

Group Type PLACEBO_COMPARATOR

0Eu/0.5ml in infants

Intervention Type BIOLOGICAL

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

Interventions

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160Eu/0.5ml in adults

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

Intervention Type BIOLOGICAL

320Eu/0.5ml in adults

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

Intervention Type BIOLOGICAL

640Eu/0.5ml in adults

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

Intervention Type BIOLOGICAL

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

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

0Eu/0.5ml in adults

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

Intervention Type BIOLOGICAL

160Eu/0.5ml in children

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

Intervention Type BIOLOGICAL

320Eu/0.5ml in children

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

Intervention Type BIOLOGICAL

640Eu/0.5ml in children

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

Intervention Type BIOLOGICAL

1280Eu/0.5ml (without adjuvant) in children

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

0Eu/0.5ml in children

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

Intervention Type BIOLOGICAL

160Eu/0.5ml in infants

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

Intervention Type BIOLOGICAL

320Eu/0.5ml in infants

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

Intervention Type BIOLOGICAL

640Eu/0.5ml in infants

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

Intervention Type BIOLOGICAL

1280Eu/0.5ml (without adjuvant) in infants

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

0Eu/0.5ml in infants

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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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


* 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


* 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)
* 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:


* 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:


* 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
Minimum Eligible Age

6 Months

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Guangxi Center for Disease Control and Prevention

OTHER_GOV

Sponsor Role collaborator

Institute of Medical Biology, Chinese Academy of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zhaojun Mo, Master

Role: PRINCIPAL_INVESTIGATOR

Guangxi Provincial Center for Diseases Control and Prevention

Locations

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Guangxi Provincial Center for Diseases Control and Prevention

Nanning, Guangxi, China

Site Status

Countries

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China

References

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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.

Reference Type DERIVED
PMID: 23372725 (View on PubMed)

Related Links

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

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.

Other Identifiers

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EV71-KMB17-I-IMB-CAMS

Identifier Type: -

Identifier Source: org_study_id

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