Phase 3 Study of BK1310 in Healthy Infants

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to: (cohort 1) evaluate safety and immunogenicity (Haemophilus influenzae type b, Hib) of BK1310. (cohort 2) evaluate efficacy and safety of BK1310 using ActHIB® and Tetrabik as a control in healthy infants.

Detailed Description
-----------------
<Cohort 1> Arm: BK1310-High. Intervention: DPT-IPV-Hib-High(Combined Vaccine) 0.5mL, subcutaneous injection, 3 times with the 3-8weeks intervals then an additional injection after 6-13 months. Arm: BK1310-Low. Intervention: DPT-IPV-Hib-Low(Combined Vaccine) 0.5mL, subcutaneous injection, 3 times with the 3-8weeks intervals then an additional injection after 6-13 months. <Cohort 2> Arm: BK1310-High or Low. Intervention: DPT-IPV-Hib-High(Combined Vaccine) or DPT-IPV-Hib-Low(Combined Vaccine) 0.5mL, subcutaneous injection, 3 times with the 3-8weeks intervals. Arm: ActHIB® and Tetrabik. Intervention: Hib vaccine and DPT-IPV 0.5mL, subcutaneous injection, 3 times with the 3-8weeks intervals.

Conditions
-----------------
Immunization; Infection

Intervention / Treatment
-----------------
* Biological: DPT-IPV-Hib-High（Combined Vaccine）
* Biological: DPT-IPV-Hib-Low（Combined Vaccine）
* Biological: Hib vaccine
* Biological: DPT-IPV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy infants aged ≥2 and <43 months at the first vaccination of the study drug (recommended: ≥2 and <7 months). Those who are applicable of the following conditions must be carefully observed before the enrollment: infants with known underlying disease such as cardiovascular disease, renal disease, hepatic disease, blood dyscrasia, respiratory disease or developmental disorder. Infants who developed fever within 2 days after any previous vaccination. Infants with history of convulsions. Written informed consent is obtained from a legal guardian (parent) Exclusion Criteria: With past diagnosis of immunodeficiency or currently under immunosuppressive treatment Have close relatives (the third degree of kinship) diagnosed with congenital immunodeficiency Possibility of anaphylaxis due to food or pharmaceuticals With experience of Hib infection, diphtheria, pertussis, tetanus or acute poliomyelitis With experience of Hib, diphteria, pertussis, tetanus or polio vaccination. Administered a live vaccine within 27 days before the first vaccination of the study drug, or inactivated vaccine or toxoid within 6 days before vaccination Administered transfusion, immunosuppressant (excluding drugs for external use), or immunoglobulin formulation Administered corticosteroid 2 mg/kg per day or more as prednisolone (excluding drugs for external use) Participated in other studies within 12 weeks before obtaining consent With the gestational age <37 weeks or weighed less than 2500 grams at birth. Considered to be not eligible by the principal investigators (sub-investigators) of the enrollment.

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 43 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: BK1310-High<br> | Biological: DPT-IPV-Hib-High（Combined Vaccine）<br> <br> * Other names: BK1310-High;|
| Experimental: Cohort 1: BK1310-Low<br> | Biological: DPT-IPV-Hib-Low（Combined Vaccine）<br> <br> * Other names: BK1310-Low;|
| Experimental: Cohort 2: BK1310-High or -Low<br>Either BK1310-High or -Low will be chosen based on the result of cohort 1 | Biological: DPT-IPV-Hib-High（Combined Vaccine）<br> <br> * Other names: BK1310-High;Biological: DPT-IPV-Hib-Low（Combined Vaccine）<br> <br> * Other names: BK1310-Low;|
| Active Comparator: Cohort 2: ActHIB® and Tetrabik<br> | Biological: Hib vaccine<br> <br> * Other names: ActHIB®;Biological: DPT-IPV<br> <br> * Other names: Tetrabik;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody prevalence rate against anti-PRP with 1 μg/mL or higher, diphtheria toxin, pertussis, tetanus toxin, and polio virus |  | 4 weeks after the primary immunization (Visit 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-PRP antibody prevalence rate with 0.15 μg/mL or higher |  | 4 weeks after the primary immunization (Visit 4) | 
| Geometric mean antibody titer of anti-PRP antibody |  | 4 weeks after the primary immunization (Visit 4) | 
| Anti-PRP antibody prevalence rate with 1 μg/mL or higher |  | 4 weeks after the booster dose (Visit 6) | 
| Anti-PRP antibody prevalence rate with 0.15 μg/mL or higher |  | 4 weeks after the booster dose (Visit 6) | 
| Geometric mean antibody titer of anti-PRP antibody |  | 4 weeks after the booster dose (Visit 6) | 
| Geometric mean antibody titer against diphtheria toxin, pertussis, tetanus toxin, and polio virus |  | 4 weeks after the primary immunization (Visit 4) | 
| Antibody prevalence rate against diphtheria toxin, pertussis, tetanus toxin, and polio virus |  | 4 weeks after the booster dose (Visit 6) | 
| Geometric mean antibody titer against diphtheria toxin, pertussis, tetanus toxin, and polio virus |  | 4 weeks after the booster dose (Visit 6) | 
| Number of participants with adverse events and adverse reactions | Cohort 1 | Through the first dose (Visit 1) to 4 weeks after the booster dose (Visit 6) | 
| Number of participants with adverse events and adverse reactions | Cohort 2 | Through the first dose (Visit 1) to 4 weeks after the primary immunization (Visit 4) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Haemophilus influenza type b, Adsorbed Diphteria-purified Pertussis-Tetanus-Inactivate poliovirus combined vaccine, Hib, DPT-IPV