Evaluation of Safety and Immunogenicity of Combined Immunization of sIPV, DTaP and HepA

Study Overview
=================
Brief Summary
-----------------
Eligible,healthy infants who have finished the 3-dose-schedule of sIPV+DTaP combined vaccination clinical trial (NCT04053010) will be recruited and divided into 4 groups, and will receive vaccination at the age of 18-month-old as follows: Group 1: sIPV + DTaP + HepA, Group 2: sIPV only, Group 3: DTaP only, Group 4: HepA only. The immunogenicity and safety of the 4 groups will be compared and analyzed before and 30-40 days after vaccination.

Detailed Description
-----------------
Following the clinical trial of Combined Immunization of sIPV and DTaP in 2019, this study recruits 600 18-month-old subjects who have received 3 doses of sIPV + DTaP, and gives them a 4th dose of vaccination (booster immunization). They are divided into 4 different groups, with 150 subjects in each group, and are innoculated with different vaccines. To be specific, group 1 receives sIPV (0.5ml)+ DTaP (0.5ml)+ HepA(0.5ml); group 2 receives sIPV (0.5ml); group 3 receives DTaP (0.5ml); group 4 receives HepA (0.5ml). Blood samples will be collected before vaccination and 30-40 days after this booster immunization. Neutralization antibody will be detected to evaluate the seroprotection rates and antibody geometric mean concentrations. The safety of both immunization schedule will be monitored as well.

Official Title
-----------------
A Randomized, Controlled, Multicenter Phase 4 Clinic Trial to Evaluate the Safety and Immunogenicity of Combined Immunization of Sabin-strain Inactivated Polio Vaccine (sIPV), Diphtheria, Tetanus, Pertussis (DTaP) Vaccine and Live Attenuated Hepatitis A Vaccine (HepA)

Conditions
-----------------
Vaccination

Intervention / Treatment
-----------------
* Biological: sIPV+DTaP+HepA
* Biological: sIPV
* Biological: DTaP
* Biological: HepA


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must have participated the clinical trial titled Clinic Trial to Evaluate the Safety and Immunogenicity of Combined Immunization of sIPV and DTaP (NCT04053010) in 2019, and have finished 3 doses of combined immunization of sIPV and DTaP; Subjects aged 18-19 months old at the date of recruitment; With informed consent form (ICF) signed by parent(s) or guardian(s); Parent(s) or guardian(s) are able to attend all planned clinical appointments and obey/follow all study instructions; Subjects have not been vaccinated with sIPV/DTaP/HepA at the age of 18-month-old yet; No less than 14 days since the last dose of vaccination; Axillary temperature ≤37.0℃. Exclusion Criteria: With a medical history with hypersensitiveness, eclampsia, epilepsy, cerebropathia and neurological illness; Allergic to any ingredient of vaccine or with allergy history to any vaccine; Subjects with immunodeficency or suspected impairment of immunologic function (e.g. caused by HIV), or subjects are in the process of immunosuppressor therapy(Taking orally injecting of steroid hormone); Administration of immunoglobulins within 30 days prior to this study; Acute febrile disease(temperature ≥ 37.0°C) or infectious disease; With a clearly diagnosed history of thrombocytopenia or other coagulopathy, may cause contraindications for subcutaneous injection; With any serious chronic illness, acute infectious diseases, or respiratory diseases; With severe cardiovascular disease, liver and kidney diseases or diabetes mellitus with complications; With any kind of infectious, purulent, or allergic skin diseases; With any other factor that makes the investigator determines the subject is unsuitable for this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Months
Maximum Age: 19 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1 (sIPV+DTaP+HepA)<br>150 subjects; simultaneously administration of sIPV+DTaP+HepA as booster immunization at the age of 18 months old, 0.5 ml each, respectively | Biological: sIPV+DTaP+HepA<br>* sIPV+DTaP+HepA at the age of 18 month old<br>|
| Active Comparator: group 2 (sIPV)<br>150 subjects; vaccination of 0.5 ml sIPV as booster immunization at the age of 18 months old | Biological: sIPV<br>* sIPV at the age of 18 month old<br>|
| Active Comparator: group 3 (DTaP)<br>150 subjects; vaccination of 0.5 ml DTaP as booster immunization at the age of 18 months old | Biological: DTaP<br>* DTaP at the age of 18 month old<br>|
| Active Comparator: group 4 (HepA)<br>150 subjects; vaccination of 0.5 ml HepA as booster immunization at the age of 18 months old | Biological: HepA<br>* HepA at the age of 18 month old<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate (sIPV) | determine the rate of positive seroconversion against poliovirus type I, II and III of the subjects | Baseline (before vaccination) results | 
| Seroconversion rate (sIPV) | determine the rate of positive seroconversion against poliovirus type I, II and III of the subjects | Results obtained 30-40 days after vaccination | 
| Seroconversion rate (DTaP) | determine the positive seroconversion rate of anti-pertussis toxoid , anti- filamentous hemagglutinin, anti-diphtheria toxoid and anti-tetanic antibody of the subjects | Baseline (before vaccination) results | 
| Seroconversion rate (DTaP) | determine the positive seroconversion rate of anti-pertussis toxoid , anti- filamentous hemagglutinin, anti-diphtheria toxoid and anti-tetanic antibody of the subjects | Results obtained 30-40 days after vaccination | 
| Seroconversion rate (HepA) | determine the rate of positive seroconversion rate of anti-hepatitis A virus antibody of the subjects | Baseline (before vaccination) results | 
| Seroconversion rate (HepA) | determine the rate of positive seroconversion rate of anti-hepatitis A virus antibody of the subjects | Results obtained 30-40 days after vaccination | 
| Geometric Mean Concentration (GMC) (sIPV) | GMCs of poliovirus type I, II and III of the subjects | Baseline (before vaccination) results | 
| Geometric Mean Concentration (GMC) (sIPV) | GMCs of poliovirus type I, II and III of the subjects | Results obtained 30-40 days after vaccination | 
| Geometric Mean Concentration (GMC) (DTaP) | GMCs of anti-pertussis toxoid , anti- filamentous hemagglutinin, anti-diphtheria toxoid and anti-tetanic antibody of the subjects | Baseline (before vaccination) results | 
| Geometric Mean Concentration (GMC) (DTaP) | GMCs of anti-pertussis toxoid , anti- filamentous hemagglutinin, anti-diphtheria toxoid and anti-tetanic antibody of the subjects | Results obtained 30-40 days after vaccination | 
| Geometric Mean Concentration (GMC) (HepA) | GMCs of anti-hepatitis A virus antibody of the subjects | Baseline (before vaccination) results | 
| Geometric Mean Concentration (GMC) (HepA) | GMCs of anti-hepatitis A virus antibody of the subjects | Results obtained 30-40 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events Following Immunization (AEFI) | analyse the incidence of adverse events following immunization, both solicited and unsolicited | 0-6 months |