The Phase IVc of Inactivated Enterovirus 71 Vaccine (Human Diploid Cell)

Study Overview
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Brief Summary
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Enterovirus 71 (EV71), a major pathogen causing hand-foot-and-mouth disease (HFMD) worldwide, is a member of the Human Enterovirus species A, family Picornaviridae. Its infection occasionally leads to severe diseases and death, with central nervous system (CNS) damage. Recently, except of inactivated vaccine, several EV71 vaccine candidates have been evaluated in animals but no final results of clinical trials, such as attenuated vaccine, subunit vaccine. A formalin-inactivated EV71 vaccine (Human Diploid cell, KMB-17 Cell) has been finished phase I, II and III clinical trials and licensed by SFDA in China at Dec. 3, 2015. Based on the results of clinical trials, the protective efficacy of inactivated EV71 vaccine is 97% against HFMD caused by EV71. The phase IV clinical trial has been carried out from July 2016. The purpose of phase IVc is to evaluated the immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old) in Hubei Province, China.

Detailed Description
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There are two parts of phase IVc clinical trials have been performed. First, to evaluate the immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old), within 56-day-post-immunized. Second, to long-term immunogenicity of the inactive EV71 vaccine in large scale population of Chinese children (from 6 to 71 months old).

Official Title
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Study on Immunogenicity of Inactivated Enterovirus 71 (EV71) Vaccine (Human Diploid Cell, KMB-17) in Large-scale Healthy Children in China

Conditions
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Hand, Foot and Mouth Disease (HFMD)

Intervention / Treatment
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* Biological: Inactivated EV71 vaccine (human diploid cell, KMB-17)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects (6-71 months old children) as established by medical history and clinical examination 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 14-month visit (and receive blood, stool (or specimens by means of a swab) tests according to program requirements in immunogenicity observation group) Exclusion Criteria: Allergy or serious side-effects to a vaccine or any ingredient of vaccine Epilepsy, seizures, convulsions, neurological illness Congenital or hereditary immunodeficiency Autoimmune disease 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 15 days Any prior administration of subunit or inactivated vaccines in last 7 days 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 ﹥140 mmHg and/ or diastolic blood pressure ﹥90 mmHg; systolic blood pressure ﹤90 mmHg and/or diastolic blood pressure ﹤60 mmHg Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives take part into other vaccine or drug clinical trials in last half year

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 71 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Inactivated EV71 vaccine (KMB-17 cells)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vaccine (3.0EU)<br>healthy children (6-71 months old) have been injected by inactivated EV71 vaccine (KMB-17) of 3.0 EU (neutralization antibodies titer unit; 100 U in phase III clinical trials, or 320 EU (Elisa assay unit) in phase I and II clinical trials) | Biological: Inactivated EV71 vaccine (human diploid cell, KMB-17)<br>* 3.0 EU of inactivated enterovirus 71 vaccine (KMB-17) on day 0, 28.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the seroconversion rate of anti-EV71 antibodies in serum of children | Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated. | at 28 days after finishing 2 doses immunization | 
| Evaluate the antibody titers of anti-EV71 antibodies in serum of children | Bloods were obtained at 0 and 56 days after first vaccination. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated. | at 28 days after finishing 2 doses immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate long-term of the seroconversion rate of anti-EV71 antibodies in serum of children | Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated. | Up to 3 years after finishing 2 doses immunization | 
| Evaluate long-term of the antibody titers of anti-EV71 antibodies in serum of children | Bloods were obtained at 0, 28 and 56 days after first vaccination, and 180, 360 and 720 days after 2 doses immunization. The antibody titers were tested in serum of children. And the seroconversion rate of anti-EV71 antibodies was calculated. | Up to 3 years after finishing 2 doses immunization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, immunogenicity, Hand, Foot and Mouth Disease (HFMD)