DTaP-IPV/Hib Vaccine Primary & Booster Vaccinations Versus Co-administration of DTaP-IPV and Hib Vaccine in Japanese Infants

Study Overview
=================
Brief Summary
-----------------
Primary objective: To demonstrate the non-inferiority in terms of seroprotection rates (Hib antigen (PRP), Diphtheria, Tetanus, and Pertussis antigens (PT and FHA), and polio types 1, 2 and 3 antigens) of investigational arm (Group A: DTaP-IPV/Hib) versus control arm (Group B: DTaP-IPV and Hib vaccines administered at separate sites), one month after the primary vaccination (all antigens). Secondary objectives: To describe immune responses against all vaccine antigens with no pre-specified hypothesis, and at all time points (pre-dose 1, post-dose 3, pre-dose 4 and post-dose 4) in the two study groups (Group A and Group B). To describe the safety after each dose of each vaccine in the two study groups (Group A and Group B). To describe immune responses against all vaccine antigens with no pre-specified hypothesis, and at all time points (pre-dose 1, post-dose 3, pre-dose 4 and post-dose 4 (Group C)

Detailed Description
-----------------
Participants will be enrolled in two steps (Cohort 1 and Cohort 2). Step one will enroll Cohort 1 made of 40 participants randomized in two groups with a 1:1 ratio. After review of the local and systemic adverse events occurring during the 7 Days following the first dose administered in these subjects, 2nd vaccination of Cohort 1 participants will resume and enrollment of the participants of Cohort number 2 will start. Step two will enroll Cohort 2 made of subjects randomized in two groups with a 1:1 ratio. A sub-study Group C will be enrolled and will receive the vaccine by intramuscular route.

Official Title
-----------------
Immunogenicity and Safety of the DTaP-IPV/Hib Vaccine SP0204) Given as Three-dose Primary and One-dose Booster Vaccinations Versus Co-administration of DTaP-IPV Vaccine (DD-687) and Hib Vaccine (DF-098) in Infants in Japan

Conditions
-----------------
Tetanus, Diphtheria, Pertussis, Poliomyelitis, Bacterial Meningitis

Intervention / Treatment
-----------------
* Biological: DTaP-IPV/Hib Combined vaccine
* Biological: DTaP-IPV vaccine and Hib vaccine
* Biological: DTaP-IPV/Hib Combined vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 2 months to 68 months inclusive (recommended 3 to 8 months for Groups A and B; 2 months for Group C) on the day of inclusion Informed consent form signed by the parent(s) or other legal representative Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: Fever ≥ 37.5°C (axillary temperature) on the day of inclusion Any serious disease whether acute or chronic Past or current medical history of Guillain-Barre syndrome, acute thrombocytopenic purpura or encephalopathy History of diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b infections History of a life threatening reaction to a vaccine containing the same substances of the study vaccine History of anaphylaxis to any of the study vaccine components Previous vaccination against diphtheria, tetanus, pertussis, poliomyelitis or Haemophilus influenzae type b infections with a trial vaccine or another vaccine Congenital or current acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroids therapy Participation in another clinical trial preceding the trial inclusion Planned participation in another clinical trial during the present trial period Blood or blood-derived products received in the past or current or planned administration during the trial (including immunoglobulins) Any vaccination with live vaccines within the past 27 days preceding the first trial vaccination Any vaccination with inactivated vaccines within the past 6 days preceding the first trial vaccination Clinical or known serological evidence of systemic illness including Hepatitis B, Hepatitis C and/or HIV infection Subject ineligible according to the Investigator's clinical judgment Identified as employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family member (i.e., immediate, husband, wife and their children, adopted or natural) of the employees or the Investigator.

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 68 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A (SP0204)<br>Participants will receive DTaP-IPV/Hib vaccine administered subcutaneously | Biological: DTaP-IPV/Hib Combined vaccine<br>* 0.5 mL, Subcutaneously. 3 times, each given 3 to 8 weeks apart<br>* Other names: SP0204;|
| Active Comparator: Group B (control)<br>Participants will be given a co-administration of DTaP-IPV vaccine and Hib vaccine subcutaneously | Biological: DTaP-IPV vaccine and Hib vaccine<br>* 0.5 mL each, Subcutaneously, 3 times, each given 3 to 8 weeks apart<br>* Other names: DD 687; DF 098;|
| Experimental: Group C<br>Participants will receive DTaP-IPV/Hib vaccine administered intramuscularly | Biological: DTaP-IPV/Hib Combined vaccine<br>* 0.5 mL, Intramuscularly. 3 times, each given 4 to 8 weeks apart<br>* Other names: SP0204;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with anti-Diphtheria level ≥ 0.1 IU/mL post-dose 3 | Anti-Diphtheria antibody titers will be assayed by neutralization test on Vero cells culture in comparison to the WHO equine antitoxin standard (seroneutralization) | 21 Days post-dose 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Seroprotection to vaccine antigens following vaccination | Seroprotection is defined as: percentage of participants with anti-Diphtheria and anti Tetanus antibody levels ≥0.01, ≥0.1 and ≥1.0 IU/mL | Day 0 (pre-vaccination ) and 21 Days post-dose 3 | 
| Geometric Mean Titer (GMT) of antibodies to vaccine antigens following vaccination | Anti-Diphtheria antibody titers will be assayed by neutralization test on Vero cells culture in comparison to the WHO equine antitoxin standard (seroneutralization) | 21 Days post-dose 3 | 
| Information concerning the safety in terms of solicited injection site and systemic reactions, unsolicited adverse events, and serious adverse events post vaccination with DTaP IPV/Hib vaccine. | Solicited injection site reactions: Tenderness, Erythema, Swelling and Induration; Solicited Systemic Reactions: Fever (Temperature), Vomiting, Crying abnormal, Drowsiness, Appetite lost and Irritability. | Day 0 (post-vaccination) up to 21 days post each vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Tetanus, Diphtheria, Pertussis, Poliomyelitis, Bacterial meningitis, DTaP-IPV/Hib Combination vaccine