Immunogenicity Study of Antibody Persistence and Booster Effect of DTaP-HB PRP T Combined Vaccine in Filipino Infants

Study Overview
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Brief Summary
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DTaP-HB-PRP T combined vaccine is being developed in order to comply with expanding programs for immunization in infancy, while offering the benefit of a reduced number of injections, and potentially of an increased acceptance. Primary Objectives: To describe the antibody persistence at 12 to 18 months following a three-dose primary series vaccination of either DTaP-HB-PRP T or Tritanrix-Hep B/Hib™ given at 6, 10 and 14 weeks of age, and one dose of Hepatitis B (Hep B) vaccine given at birth. To describe the effect of a booster dose of DTaP-HB-PRP T on immunogenicity at 12 to 18 months following a three-dose primary series vaccination of either DTaP-HB-PRP T or Tritanrix HepB/Hib™ given at 6, 10 and 14 weeks of age, and one dose of Hep B vaccine given at birth. Secondary Objective: To describe the safety profile of the booster dose of the DTaP-HB-PRP T vaccine when administered concomitantly with Oral Polio Vaccine (OPV).

Detailed Description
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This study will assess the immunogenicity and reactogenicity of the investigational DTaP-HB-PRP T combined vaccine when given as a booster dose, concomitantly with OPV, in Filipino children previously primed at 6, 10, and 14 weeks with the investigational DTaP-HB-PRP T combined vaccine or Tritanrix-Hep B/Hib™ vaccine and having received a first dose of Hep B vaccine (Recomvax B™) at birth in a previous study, AL201 (NCT00348881).

Official Title
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Immunogenicity Study of the Antibody Persistence and Booster Effect of DTaP-Hep B-PRP-T Combined Vaccine at 12 to 18 Months of Age Following a Primary Series at 6, 10 and 14 Weeks of Age in Healthy Filipino Infants Having Received Hepatitis B Vaccine at Birth

Conditions
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Diphtheria, Tetanus, Pertussis, Hepatitis B, Influenza

Intervention / Treatment
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* Biological: DTaP-HB PRP T Combined Vaccine
* Biological: DTaP-HB-PRP T vaccine
* Biological: Oral Polio Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Toddler aged 12 to 18 months of age on the day of inclusion (range: 365 days to 578 days of age inclusive) Participated in the AL201 study and completed the three-dose primary series with either DTaP-HB-PRP T or Tritanrix-HepB/Hib™, and OPV, at 6, 10 and 14 weeks of age, and received hepatitis B vaccine at birth Informed consent form signed by one parent or legal representative if appropriate (independent witness mandatory if parent is illiterate) Able to attend all scheduled visits and to comply with all trial procedures Exclusion Criteria: Participation in another clinical trial in the 4 weeks preceding the trial vaccination Planned participation in another clinical trial during the present trial period Congenital or acquired immunodeficiency, immunosuppressive therapy such as long-term (for more than 2 weeks) systemic corticosteroid therapy within the preceding 3 months Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to a vaccine containing the same substances Chronic illness at a stage that could interfere with trial conduct or completion Blood or blood-derived products received in the last 3 months Any vaccination in the 4 weeks preceding the trial vaccination Vaccination planned in the 4 weeks following the trial vaccination Febrile (temperature ≥ 38.0°C) or acute illness on the day of inclusion History of documented diphtheria, tetanus, pertussis, Haemophilus influenzae type b, hepatitis B or poliomyelitis infection(s) (confirmed either clinically, serologically, or microbiologically) Vaccination with a vaccine containing diphtheria, tetanus, pertussis, Haemophilus influenzae type b, hepatitis B or poliovirus 3 types antigen, since the end of the primary series Thrombocytopenia or a bleeding disorder contraindicating IM vaccination Serious adverse event related to any vaccination in the AL201 study.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>DTaP-Hep B-PRP-T + OPV vaccine group | Biological: DTaP-HB PRP T Combined Vaccine<br>* 0.5 mL, Intramuscular (IM)<br>Biological: Oral Polio Vaccine<br>* Oral co-administered with study vaccine.<br>|
| Experimental: Group 2<br>Tritanrix-HepB/Hib™ + OPV vaccine group | Biological: DTaP-HB-PRP T vaccine<br>* 0.5 mL, IM<br>Biological: Oral Polio Vaccine<br>* Oral co-administered with study vaccine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Antibody Persistence and Immunogenicity Booster Response to Vaccination With DTaP-Hep B-PRP T Concomitantly With Oral Polio Vaccine (OPV) | Immunogenicity was assessed by means of radioimmunoassay (RIA) for anti-Hepatitis B (Hep Bs) and anti-PRP antibodies, enzyme immunoassay (EIA) for anti-Tetanus, and serum neutralization (SN) for anti-Diphtheria. Booster responses defined as titers ≥ 10 mIU/mL for anti-Hep Bs; ≥ 0.15 μg/mL for anti-PRP; ≥ 0.01 IU/mL for anti-Tetanus and anti-Diphtheria; Pertussis Toxoid and Filamentous Hemagglutinin (FHA) 4-fold increase and booster response. | Day 0 (pre-vaccination) and Day 28 post-booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of Vaccine Antibodies After Booster Vaccination With DTaP-Hep B-PRP T Combined Vaccine Concomitantly With Oral Polio Vaccine (OPV) | Immunogenicity was assessed by means of radioimmunoassay (RIA) for anti-Hepatitis B (Hep Bs) and anti-PRP antibodies, enzyme immunoassay (EIA) for anti-Tetanus, and serum neutralization (SN) for anti-Diphtheria following the booster vaccination. | Day 0 (pre-vaccination) and Day 28 post-vaccination | 
| Number of Participants Reporting Solicited Injection Site Reaction or Systemic Reactions Following Vaccination With a Booster Dose of the DTaP-Hep B-PRP T Combined Vaccine Concomitantly With Oral Polio Vaccine (OPV) | Solicited injection site reactions: Pain, Erythema, and Swelling; Solicited systemic reactions; Pyrexia (temperature), Vomiting, Abnormal Crying, Drowsiness, Loss of Appetite, and irritability. Grade 3 reactions are defined as: Pain - cries when injected limb is moved; Erythema and Swelling - ≥ 5cm; Fever - rectal temperature ≥ 39.5ºC; Vomiting - ≥6 episodes per 24 hours; Crying - inconsolable crying for >3 hours; Somnolence - sleeping most of the time or difficulty to wake up; Anorexia - refuses ≥3 feeds; and Irritability - inconsolable. | Day 0 up to Day 7 after vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Tetanus, Pertussis, Hepatitis B Hansenula (HB), Haemophilus influenzae type b