Safety and Immunogenicity of an Inactivated EV71 Vaccine in Infants

Study Overview
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Brief Summary
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A randomized, placebo-controlled, double-blind clinical trial is to evaluate the safety and immunogenicity of a new inactivated EV71 vaccine developed by Sinovac Biotech CO., LTD.

Conditions
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Infection, Viral, Enterovirus

Intervention / Treatment
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* Biological: 100U EV71 vaccine with adjuvant
* Biological: 200 U EV71 vaccine with adjuvant
* Biological: 400U EV71 vaccine with adjuvant
* Biological: 200U EV71 vaccine without adjuvant
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females, aged from 6 months to 11 years old Health is determined by medical history, physical examination, laboratory examination and clinical judgment of the investigator Provided legal identification for the sake of recruitment. Subjects and/or parent(s)/legal guardian(s) are able to understand and sign informed consents. Birth weight more than 2500 grams Exclusion Criteria: History of Hand-foot-mouth Disease Subject that has allergic history of vaccine, or allergic to any ingredient of vaccine Serious adverse reactions to vaccines such as anaphylaxis, hives, respiratory difficulty, angioedema, or abdominal pain Congenital malformations or developmental disorders, genetic defects, or severe malnutrition Epilepsy, seizures or convulsions history, or family history of mental illness Autoimmune disease or immunodeficiency, or parents, brothers and sisters have autoimmune diseases or immunodeficiency History of asthma, angioedema, diabetes or malignancy History of thyroidectomy or thyroid disease that required medication within the past 12 months Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws Asplenia, functional asplenia or any condition resulting in the absence or removal the spleen Acute illness or acute exacerbation of chronic disease within the past 7 days Any history of immunosuppressive medications or cytotoxic medications or inhaled corticosteroids within the past six months (with the exception of corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for an acute uncomplicated dermatitis) History of any blood products within 3 months Administration of any live attenuated vaccine within 28 days Administration of subunit or inactivated vaccines ,e.g., pneumococcal vaccine, or allergy treatment within 14 days Axillary temperature > 37.0 centigrade before vaccination Abnormal laboratory parameters before vaccination Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 100U EV71 vaccine with adjuvant<br>120 infants received 2 doses of 100U EV71 vaccine with aluminium hydroxide adjuvant 28 days apart | Biological: 100U EV71 vaccine with adjuvant<br>* inactivated vaccine (vero cell) against EV71 of 100U /0.5ml, two doses, 28 days interval<br>* Other names: EV71 vaccine;|
| Experimental: 200 U EV71 vaccine with adjuvant<br>120 infants received 2 doses of 200U EV71 vaccine with aluminium hydroxide adjuvant 28 days apart | Biological: 200 U EV71 vaccine with adjuvant<br>* inactivated vaccine (vero cell) against EV71 of 200U /0.5ml, two doses, 28 days interval<br>* Other names: EV71 vaccine;|
| Experimental: 400U EV71 vaccine with adjuvant<br>120 infants received 2 doses of 400U EV71 vaccine with aluminium hydroxide adjuvant 28 days apart | Biological: 400U EV71 vaccine with adjuvant<br>* inactivated vaccine (vero cell) against EV71 of 400U /0.5ml, two doses, 28 days interval<br>* Other names: EV71 vaccine;|
| Experimental: 200U EV71 vaccine without adjuvant<br>60 infants received 2 doses of 200U EV71 vaccine without adjuvant 28 days apart | Biological: 200U EV71 vaccine without adjuvant<br>* inactivated vaccine (vero cell) against EV71 without adjuvant of 200U /0.5ml, two doses, 28 days interval<br>* Other names: EV71 vaccine;|
| Placebo Comparator: Placebo<br>120 infants received 2 doses of placebo 28 days apart. | Biological: Placebo<br>* 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 |
| --- | --- | --- |
| Neutralization antibody geometric mean titer in infants 28 days after immunization with EV71 vaccine with or without aluminium hydroxide adjuvant | Primary immunogenicity end point were geometric mean titer of neutralization antibody againt EV71 virus >= 1:8 | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rates and severity of solicited adverse events in infants following immunization as a Measure of Safety and Tolerability | solicited local adverse events include Pain, Redness, Swelling, Induration, Rash, Pruritus at injection site. solicited general adverse events include Fever, Nausea, Vomiting, Diareahhea, Decreased appetite, Be agitated (irritability, abnormal crying), fatigue, allergy | 6 months |