Safety and Immunogenicity of IPOVAC in Young Children

Study Overview
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Brief Summary
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A dose escalating study with 3 different dosing regimens of the studied vaccine (IPOVAC- POLYVAC-Vietnam) and a licensed vaccine (IMOVAC-Sanofi Pasteur- France) is conducted in Vietnamese children, aged 2 months and above to assess the safety and immunogenicity. Two hundred and forty children are enrolled and placed randomly into 4 groups (60 children/group), each of which receive 3 doses of vaccine subcutaneously, at 4 week interval. Safety issues included immediate reaction at the site of injection and systemic reaction within 30 min of administration, within 7 days after each dose, unexpected event occur within 30 days of each dose, SAE (from start of dose 1 to 30 days after dose 3), blood cell count, urea, ALT,AST. Immunogenicity outcomes include seroconversion of neutralising antibodies for each of vaccine serotypes.

Detailed Description
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The use of oral poliomyelitis vaccine (OPV) in Vietnam expanded immunisation program has resulted in successful eradication of polio in Vietnam. However due to the concern of OPV-related poliomyelitis cases occurred worldwide, WHO has recommended the countries to gradually change to inactivated polio vaccine (IPV). In Vietnam, POLYVAC has been approved and sponsored by the Ministry of Science and Technology to produce IPV under Japanese technology. The vaccine consisting of 3 serotypes (Serotype 1,2 and 3) has been proven safety in volunteer adults. In this study, a dose escalating study with 3 different dosing regimens of the studied vaccine (IPOVAC) and a licensed vaccine (IMOVAC-Sanofi Pasteur- France) is conducted in Vietnamese children, aged 2 months and above to assess the safety and immunogenicity. Two hundred and forty children are enrolled and placed randomly into 4 groups (60 children/group), each of which receive 3 doses of vaccine subcutaneously, at 4 week interval. Safety issues evaluated include immediate reaction at the site of injection and systemic reaction within 30 min of administration, within 7 days after each dose, unexpected event occur within 30 days of each dose, SAE (from start of dose 1 to 30 days after dose 3), blood cell count, urea, ALT,AST. Seroconversion rates of neutralising antibodies for each of vaccine serotypes are to be assessed.

Official Title
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Safety and Immunogenicity of an Inactivated Poliomyelitis Vaccine (IPOVAC) in Vietnamese Children

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: IMOVAC-POLIO
* Biological: IPOVAC 1.5:5:5
* Biological: IPOVAC, 3:10:10
* Biological: IPOVAC, 6:20:20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children of both sexes, 2 months of ages Full term babies (>=37 weeks) Weight at birth (>=2500gr) Have not been vaccinated with polio vaccine or vaccine containing poliovirus components Not currently have acute infection (assessed via clinical check up and asking parents/care givers about health history before enrolment Parents/legal guardians agree to participate their children in this study and sign the informed consent. Exclusion Criteria: Currently have chronic diseases (cardiovascular, liver and spleen related etc) Use (orally or through infection) with corticoid containing drug (>1mg/kg dose) Use of immunocompromised treatment within 4 weeks of enrolment Being immunocompromised and autoimmune diseases (HIV, lupus) the history of immunocompromised in the family history of high fever Allergic for any vaccine component Fever (>38oC) within 3 days before vaccination or at enrolment Malnourished (3rd level or above) Blood disorder use of vaccines which have not been licences 7 days before enrolment in this study

Ages Eligible for Study
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Minimum Age: 2 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPOVAC 1.5:5:5<br>IPOVAC- POLYVAC Vietnam Composition: Type 1: 1.5DU, Type 2: 5DU, Type 3:5DU Subcutaneous inj 0.5ml/dose, 3 doses, interval 30days +/- 3 days Liquid form | Biological: IPOVAC 1.5:5:5<br>* IPOVAC- POLYVAC Vietnam Composition: Type 1: 1.5DU, Type 2: 5DU, Type 3:5DU Subcutaneous inj 0.5ml/dose, 3 doses, interval 30days +/- 3 days Liquid form<br>* Other names: IPOVAC-low;|
| Experimental: IPOVAC 3:10:10<br>IPOVAC- POLYVAC Vietnam Composition: Type 1: 3DU, Type 2: 10DU, Type 3:10DU Subcutaneous inj 0.5ml/dose, 3 doses, interval 30days +/- 3 days Liquid form | Biological: IPOVAC, 3:10:10<br>* IPOVAC- POLYVAC Vietnam Composition: Type 1: 3DU, Type 2: 10DU, Type 3:10DU Subcutaneous inj 0.5ml/dose, 3 doses, interval 30days +/- 3 days Liquid form<br>* Other names: IPOVAC-medium;|
| Experimental: IPOVAC 6:20:20<br>IPOVAC- POLYVAC Vietnam Composition: Type 1: 6DU, Type 2: 20DU, Type 3:20DU Subcutaneous inj 0.5ml/dose, 3 doses, interval 30days +/- 3 days Liquid form | Biological: IPOVAC, 6:20:20<br>* IPOVAC- POLYVAC Vietnam Composition: Type 1: 6DU, Type 2: 20DU, Type 3:20DU Subcutaneous inj 0.5ml/dose, 3 doses, interval 30days +/- 3 days Liquid form<br>* Other names: IPOVAC-high;|
| Active Comparator: IMOVAC-POLIO<br>IMOVAC-POLIO (Sanofi Pasteur), liquid form composition: Type 1 (Mahoney) 40DU, Type 2 (MEF1) 8DU, Type 3 (Saukett) 32 DU, Subcutaneous route 0.5ml/dose, 3 doses, 4-week interval | Biological: IMOVAC-POLIO<br>* IMOVAC-POLIO (Sanofi Pasteur), liquid form composition: Type 1 (Mahoney) 40DU, Type 2 (MEF1) 8DU, Type 3 (Saukett) 32 DU, Subcutaneous route 0.5ml/dose, 3 doses, 4-week interval<br>* Other names: IMOVAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events after each dose of vaccine | Number of participants with treatment-related adverse events after each dose of vaccine, immediately after vaccination (within 30 min), within 7 days and 30 days of vaccination, as assessed by CTCAE v.4.0 | Upto 30 days after each dose | 
| Number of participants with 4-fold or more increase in in antibody titers after 2 or 3 doses of vaccine (compared to pre-vaccination) | Seroconversion rate of each IPOVAC regimen and IMOVAC after 2 or 3 doses of vaccines | Upto 30 days after the final dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related SAE after each vaccination dose | Number of participants with treatment-related SAE after each vaccination doses of IPOVAC compared to that of IMOVAC, as assessed by CTCAE ver 4.0 | Upto 30 days after vaccine dose | 
| Number of participants with abnormal laboratory value | Numbers of participants with abnormal laboratory values (blood cell counts, urea concentration, liver function (ALT, AST concentration) when administered with different IPOVAC formulations and with IMOVAC before and after each dose of vaccination | Upto 30 days after each vaccine dose |