A Study to Evaluate the Immunogenicity and Safety of EV71 Vaccine in Pediatric Subjects

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 Al(OH)3 at 0.5-μg and 1-μg dose in children aged 3 to 6 years old and 2 to 35 months old infants/toddlers.

Official Title
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An Open-Label, Dose-Finding, Phase II Study to Evaluate the Immunogenicity and Safety of the Bioreactor-generated EV71 Vaccine in Pediatric Subjects Aged 3 to 6 Years and 2 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 AI(OH)3] per dose)
* Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] 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,and from 2 to 35 months old (i.e. ≥ 2 months old and < 36 months old) for Part B at the time of first vaccination. Subject's guardians are able and willing to comply with study procedures and provide the signed informed consent. Subject is able and can 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,and 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 hemostatic difficulties with IM injections or blood draws. Any acute infections 7 days prior to administrating 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 vaccines within 14 days prior to randomization. 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 or planned use during the study period. Subjects who had ever received investigational EV-71 vaccine prior to randomization. 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: 2 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 AI(OH)3] 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 AI(OH)3] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group A3<br>3 to 6 years | Biological: EV71 vaccine ([1 μg total protein ] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group B1<br>2 to 35 months | Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AI(OH)3] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group B2<br>2 to 35 months | Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] per dose)<br>* Two vaccinations at 28 days apart<br>|
| Experimental: Group B3<br>2 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 |
| --- | --- | --- |
| Serum neutralizing antibody titers (NT) induced by the EV71 vaccine | Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 56 | Day 56 | 
| Seroconversion rate (SCR) based on neutralizing antibody titers | Evaluate the immunogenicity change of SCR from baseline on Day 56 | Day 56 | 
| Serum neutralizing antibody titers (NT) induced by the EV71 vaccine | Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 28 | Day 28 | 
| Serum neutralizing antibody titers (NT) induced by the EV71 vaccine | Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 196 | Day 196 | 
| Seroconversion rate (SCR) based on neutralizing antibody titers | Evaluate the immunogenicity change of SCR from baseline on Day 28 | Day 28 | 
| Seroconversion rate (SCR) based on neutralizing antibody titers | Evaluate the immunogenicity change of SCR from baseline on Day 196 | Day 196 | 

Secondary 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 | 
| The occurrence of EV 71 breakthrough infection after Visit 3 |  | Day 57 to Day 364 | 
| Serum neutralizing antibody titers (NT) induced by the EV71 vaccine | Evaluate the immunogenicity of serum neutralization antibody titer induced by the EV 71 vaccine on Day 364 | Day 364 | 

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