A Phase II Clinical Trial for Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children and Infants

Study Overview
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Brief Summary
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Hand, foot, and mouth disease (HFMD) is a common viral illness in infants and children caused by viruses that belong to the enterovirus genus of the picornavirus family. Although most HFMD cases do not result in serious complications, outbreaks of HFMD caused by enterovirus 71 (EV71) can present with a high rate of neurological complications, including meningoencephalitis, pulmonary complications, and can even cause infant death. HFMD caused by EV71 has become a major emerging infectious disease in Asia and the highly pathogenic potential of EV71 clearly requires the attention of world medical community. The phase I study of inactivated vaccine (vero cell) against EV71 has completed last month in Jiangsu Province in China. The data from the phase I study suggested that the inactivated EV71 vaccine had a clinically acceptable safety and good immunogenicity for healthy Chinese children and infants. In order to provide more evidence for the immunogenicity of the vaccine, to further explore the probable immunizing dose and the safety profile of this vaccine, a phase II clinical trial is planed to conduct.

Official Title
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A Phase II Clinical Trial for Inactivated Vaccine (Vero Cell) Against EV71 in Chinese Children and Infants

Conditions
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Immunogenicity, Safety

Intervention / Treatment
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* Biological: 160U /0.5ml EV71 Vaccine
* Biological: 320U /0.5ml EV71 vaccine
* Biological: 640U /0.5ml EV71 vaccine
* Biological: (without adjuvant) 640U /0.5ml
* Biological: 0/0.5ml placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For children group (aged from 12-36 months): Healthy children aged from 12 to 36 months old as established by medical history and clinical examination The subjects' guardians are able to understand and sign the informed consent Had never received the vaccine against EV71 Subjects who can and will comply with the requirements of the protocol Subjects with temperature <=37.0°C on axillary setting For infants group (aged from 6-11 months): Healthy infants aged from 6 to 11 months old as established by medical history and clinical examination The subjects' guardians are able to understand and sign the informed consent Had never received the vaccine against EV71 Subjects who can and will comply with the requirements of the protocol Subjects with temperature <=37.0°C on axillary setting Exclusion Criteria: For children group (aged from 12-36 months): Subject who has a medical history of HFMD <= 37 weeks gestation Subjects with a birth weight <2.5 kg Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine Family history of seizures or progressive neurological disease Family history of congenital or hereditary immunodeficiency Severe malnutrition or dysgenopathy Major congenital defects or serious chronic illness, including perinatal brain damage Autoimmune disease Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws Any acute infections in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6month Any prior administration of blood products in last 3 month Any prior administration of other research medicines in last 1 month Any prior administration of attenuated live vaccine in last 28 days Any prior administration of subunit or inactivated vaccines in last 14 days, such as pneumococcal vaccine Under the anti-TB prevention or therapy Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives For infants group (aged from 6-11 months): Subject who has a medical history of HFMD <= 37 weeks gestation Subjects with a birth weight <2.5 kg Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine Family history of seizures or progressive neurological disease Family history of congenital or hereditary immunodeficiency Severe malnutrition or dysgenopathy Major congenital defects or serious chronic illness, including perinatal brain damage Autoimmune disease Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws Any acute infections in last 7 days Any prior administration of immunodepressant or corticosteroids in last 6month Any prior administration of blood products in last 3 month Any prior administration of other research medicines in last 1 month Any prior administration of attenuated live vaccine in last 28 days Any prior administration of subunit or inactivated vaccines in last 14 days, such as pneumococcal vaccine Under the anti-TB prevention or therapy Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives Exclusion Criteria for the second dose: Had any Grade 3 or Grade 4 adverse reaction within 7 days after first dose Any situation meet the exclusion criteria stated in the exclusion criteria for first dose Had any SAE related to first dose during the following-up of first dose Any condition that in the opinion of the investigator, or IRB

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 36 Months

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: 160U /0.5ml in children (from 12 to 36 months old)<br>inactivated vaccine(vero cell) against EV71 of 160U /0.5ml in 120 children aged 12-36 months old on day0,28 | Biological: 160U /0.5ml EV71 Vaccine<br>* inactivated vaccine (vero cell) against EV71 of 160U /0.5ml, two doses, 28 days interval<br>|
| Experimental: 320U /0.5ml in children (from 12 to 36 months old)<br>inactivated vaccine(vero cell) against EV71 of 320U /0.5ml in 120 children aged 12-36 months old on day0,28 | Biological: 320U /0.5ml EV71 vaccine<br>* inactivated vaccine(vero cell) against EV71 of 320U /0.5ml, two doses, 28 days interval<br>|
| Experimental: 640U /0.5ml in children (from 12 to 36 months old)<br>inactivated vaccine(vero cell) against EV71 of 640U /0.5ml in 120 children aged 12-36 months old on day0,28 | Biological: 640U /0.5ml EV71 vaccine<br>* inactivated vaccine (vero cell) against EV71 of 640U /0.5ml, two doses, 28 days interval<br>|
| Experimental: (without adjuvant) 640U /0.5ml in children (12-36months)<br>inactivated vaccine(vero cell) against EV71 of (without adjuvant) 640U /0.5ml in 120 children aged 12-36 months old on day0,28 | Biological: (without adjuvant) 640U /0.5ml<br>* inactivated vaccine (vero cell) against EV71 of (without adjuvant) 640U /0.5ml, two doses, 28 days interval<br>|
| Experimental: 160U /0.5ml in infants (from 6 to 11 months old)<br>inactivated vaccine(vero cell) against EV71 of 160U /0.5ml in 120 infants aged 6-11 months old on day0,28 | Biological: 160U /0.5ml EV71 Vaccine<br>* inactivated vaccine (vero cell) against EV71 of 160U /0.5ml, two doses, 28 days interval<br>|
| Experimental: 320U /0.5ml in infants (from 6 to 11 months old)<br>inactivated vaccine(vero cell) against EV71 of 320U /0.5ml in 120 infants aged 6-11 months old on day0,28 | Biological: 320U /0.5ml EV71 vaccine<br>* inactivated vaccine(vero cell) against EV71 of 320U /0.5ml, two doses, 28 days interval<br>|
| Experimental: 640U /0.5ml in infants (from 6 to 11 months old)<br>inactivated vaccine(vero cell) against EV71 of 640U /0.5ml in 120 infants aged 6-11 months old on day0,28 | Biological: 640U /0.5ml EV71 vaccine<br>* inactivated vaccine (vero cell) against EV71 of 640U /0.5ml, two doses, 28 days interval<br>|
| Experimental: (without adjuvant) 640U /0.5ml in infants (from 6 to 11 months<br>inactivated vaccine(vero cell) against EV71 of (without adjuvant) 640U /0.5ml in 120 infants aged 6-11 months old on day0,28 | Biological: (without adjuvant) 640U /0.5ml<br>* inactivated vaccine (vero cell) against EV71 of (without adjuvant) 640U /0.5ml, two doses, 28 days interval<br>|
| Placebo Comparator: 0/0.5ml placebo in children (from 12 to 36 months old)<br>0/0.5ml placebo in 120 children aged 12-36 months old on day0,28 | Biological: 0/0.5ml placebo<br>* 0/0.5ml placebo, two doses, 28 days interval<br>|
| Placebo Comparator: 0/0.5ml placebo in infants (from 6 to 11 months old)<br>0/0.5ml placebo in 120 infants aged 6-11 months old on day0,28 | Biological: 0/0.5ml placebo<br>* 0/0.5ml placebo, two doses, 28 days interval<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The GMT of anti-EV71 antibodies in serum after first vaccination | to evaluate the GMT of anti-EV71 antibodies in serum 28 days after first vaccination | 28 days after first vaccination | 
| The GMT of anti-EV71 antibodies in serum after second vaccination | to evaluate the GMT of anti-EV71 antibodies in serum 28 days after second vaccination | 28 days after second vaccination | 
| Frequency of systemic and local adverse reactions after the first vaccination | Frequency of systemic and local adverse reactions in healthy Children and infants following first doses of EV71 vaccine | 28 days after the first vaccination | 
| Frequency of systemic and local adverse reactions after the second vaccination | Frequency of systemic and local adverse reactions in healthy Children and infants following second doses of EV71 vaccine | 28 days after the second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The seroconversion rate of anti-EV71 antibodies in serum after first vaccination | to evaluate the seroconversion rate of anti-EV71 antibodies in serum 28 days after first vaccination | 28 days after first vaccination | 
| The seroconversion rate of anti-EV71 antibodies in serum after second vaccination | to evaluate the seroconversion rate of anti-EV71 antibodies in serum 28 days after second vaccination | 28 days after second vaccination | 
| Frequency of adverse events and any SAE after the first vaccination | Frequency of adverse events and any SAE in healthy Children and infants following first doses of EV71 vaccine | 28 days after the first vaccination | 
| Frequency of adverse events and any SAE after the second vaccination | Frequency of adverse events and any SAE in healthy Children and infants following second doses of EV71 vaccine | 28 days after the second vaccination | 
| The clinical abnormality of hematological examination, blood biochemical test and urinalysis after first vaccination in children | to evaluate the clinical abnormality of hematological examination, blood biochemical test and urinalysis 3 days after first vaccination in children | 3 days after first vaccination | 
| The clinical abnormality of hematological examination, blood biochemical test and urinalysis after second vaccination in children | to evaluate the clinical abnormality of hematological examination, blood biochemical test and urinalysis 3 days after second vaccination in children | 3 days after second vaccination | 
| The persistence of immunogenicity of the EV71vaccine after two doses in children and infants | to evaluate the persistence of immunogenicity of the EV71vaccine after two doses in children and infants 6 months after blood collection at day 56 | 6 months after blood collection at day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunogenicity, safety, inactivated EV71 vaccine