A Study to Evaluate the Safety and Immunogenicity of EV71 Vaccine in Pediatric Subjects Aged 3 to 6 Years and 6 to 35 Months Old

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the immune response and safety profiles of two injections of EV71 vaccine administrated with or without adjuvant AlPO4 at 0.5-μg, 1-μg, 2-μg and 5-μg dose (if required) in children aged 3 to 6 years old and 0.25-μg (if required), 0.5-μg, 1-μg and 2-μg (if required) in 6 to 35 months old infants/toddlers.

Official Title
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An Open-label, Dose-finding, Phase II Study to Evaluate the Safety and Immunogenicity of EV71 Vaccine in Pediatric Subjects Aged 3 to 6 Years and 6 to 35 Months Old

Conditions
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Enterovirus Infections

Intervention / Treatment
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* Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AIPO4] per dose)
* Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AIPO4] per dose)
* Biological: EV71 vaccine ([2 μg total protein + adjuvant 150 μg AIPO4] per dose)
* Biological: EV71 vaccine (2 μg total protein per dose)
* Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AIPO4] per dose)
* Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AIPO4] per dose)
* Biological: EV71 vaccine (1 μg total protein per dose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children aged from 3 to 6 years old (i.e. ≥ 3 years old and < 7 years old) for Part A; from 6 to 35 months old (i.e. ≥ 6 months old and < 36 months old) for Part B at the time of first vaccination. Subject's guardians were able and willing to comply with study procedures and give written informed consent. Subject was able and could comply with the requirements of the protocol. Subject with body temperature ≤38°C. Exclusion Criteria: Subject with previous known exposure to Enterovirus 71 (EV71). Subject with a history of herpangina, hand-foot-mouth disease, acute hemorrhagic conjunctivitis associated with enterovirus infection in the past 3 months. Subject with gestation < 37 weeks. Subject with birth weight <2.5 kg. Subject with a history of hypersensitivity to vaccines, or a history of allergic disease or reactions likely to be exacerbated by any component of the 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. Subject diagnosed of having autoimmune disease (e.g., celiac disease, type I diabetes, lupus (SLE), juvenile dermatomyositis, scleroderma, juvenile idiopathic arthritis (JIA), immune (or idiopathic) thrombocytopenia purpura). Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws. Any acute infections 7 days prior to administrate the first vaccination. Use of any investigational product (including drug, vaccine) within 30 days prior to vaccination or planned use during the study period. Administration of any attenuated live vaccine within 7 days prior to vaccination. Use of immunoglobulins or any blood products within 3 months prior to vaccination or planned use during the study period. Chronic administration (defined as > 14 days) of immunosuppressants or other immunomodulators or systemic corticosteroids within 6 months prior to vaccination. Under anti-tuberculosis prevention or therapy. Any condition that in the opinion of the investigator may interfere with the evaluation of study objectives.

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

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A1<br>3 to 6 years | Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AIPO4] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group A2<br>3 to 6 years | Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AIPO4] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group A3<br>3 to 6 years | Biological: EV71 vaccine ([2 μg total protein + adjuvant 150 μg AIPO4] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group A4<br>3 to 6 years | Biological: EV71 vaccine (2 μg total protein per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group B2<br>6 to 35 months | Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AIPO4] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group B3<br>6 to 35 months | Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AIPO4] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group B4<br>6 to 35 months | Biological: EV71 vaccine (1 μg total protein per dose)<br>* Two vaccinations at 28 days apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited adverse events |  | 7 days after each vaccination | 
| Unsolicited adverse events |  | 28 days after each vaccination | 
| The occurrence of overall adverse events (AEs) and serious adverse event (SAEs) |  | Day 0 to Day 196 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunoglobulin G (IgG) titers induced by the EV71 vaccine ( determined by ELISA) |  | Day 28, Day 56, Day 196 | 
| serum neutralizing antibody titers (NT) induced by the EV71 vaccine |  | Day 28, Day 56, Day 196 | 
| Seroconversion rate (SCR) based on neutralizing antibody titers |  | Day 28, Day 56, Day 196 | 
| change in the laboratory results based on hematology tests in each visit |  | Day 28, Day 56, Day 196 | 
| change in the laboratory results based on biochemistry tests in each visit |  | Day 28, Day 56, Day 196 | 
| change in heart rates at each visit (for the 3 to 6 years old group only) |  | Day 28, Day 56, Day 196 | 
| change in blood pressures at each visit (for the 3 to 6 years old group only) |  | Day 28, Day 56, Day 196 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccines, Hand, Foot and Mouth Disease, EV71 enteroviruses vaccine