Immunogenicity Study of Antibody Persistence and Booster Effect of PENTAXIM™ at 18 Months in Healthy Argentinean Infants

Study Overview
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Brief Summary
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This study will assess both the antibody persistence of the investigational vaccine and the immune response and safety of a booster dose of PENTAXIM™ vaccine in 18 months-old toddlers who participated in an earlier study in order to determine if they are still protected before they receive a booster dose of D, T, IPV, pertussis or Hib vaccines and also to assess the quality of the induced immune memory in response to a booster dose of the same vaccine as in the primary series. Primary Objective: To describe the antibody persistence at 18 months of age and the booster effect of a dose of PENTAXIM™ on immunogenicity. Secondary objective: To describe the safety profile of the booster dose PENTAXIM™ in each vaccine group defined by the vaccines received during the primary series.

Official Title
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Immunogenicity Study of the Antibody Persistence and Booster Effect of PENTAXIM™ at 18 Months of Age Following a Primary Series of DTaP-IPV-HB-PRP T Combined Vaccine or of PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 Months of Age in Healthy Argentinean Infants

Conditions
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Tetanus, Diphtheria, Pertussis, Poliomyelitis, Hepatitis B

Intervention / Treatment
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* Biological: DTaP-IPV//PRP T combined vaccine
* Biological: DTaP-IPV//PRP T combined vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Toddler at 18 months of age (range: 510 days to 578 days of age inclusive) Participated in study A3L02 (NCT00831311) and has completed the three-dose primary series with either diphtheria, tetanus, pertussis (2-component acellular), recombinant Hepatitis B Hansenula and poliomyelitis vaccine adsorbed, and Haemophilus influenzae type b vaccine, conjugated to tetanus protein (DTaP-IPV-HB-PRP T) or PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 months of age Written informed consent form signed by at least one parent or by a legal representative and an independent witness Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: Participation in another clinical trial in the four weeks preceding the trial vaccination Planned participation in another clinical trial during the present trial period Congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months or long-term systemic corticosteroids therapy 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 six months Any vaccination in the four weeks preceding the trial Vaccination with a vaccine containing diphtheria, tetanus, pertussis, Haemophilus influenzae type b, polio, or hepatitis B antigen, since the end of the primary series History of documented diphtheria, tetanus, pertussis, Haemophilus influenzae type b, polio, or hepatitis B infection(s) (confirmed either clinically, serologically, or microbiologically) Thrombocytopenia or bleeding disorder contraindicating intramuscular vaccination History of seizures Fever (axillary temperature ≥37.4°C or equivalent rectal temperature ≥38.0°C) or acute illness on the day of inclusion Known contraindication to further vaccination with a pertussis vaccine such as: Encephalopathy; Inconsolable crying for >3 hours within 48 hours following vaccine injection Hypotonic hyporesponsive episode within 48 hours following vaccine injection Seizures with or without fever within three days following vaccine injection Axillary temperature >39.4°C or equivalent rectal temperature > 40.0°C within 48 hours following vaccine injection.

Ages Eligible for Study
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Minimum Age: 510 Days
Maximum Age: 578 Days

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DTacP IPV HepB PRP-T Combined Vaccine Group<br>Participant will receive a booster dose of PENTAXIM™ having received DTacP-IPV-HepB-PRP-T (primary series) in Study A3L02. | Biological: DTaP-IPV//PRP T combined vaccine<br>* 0.5 mL, Intramuscular<br>* Other names: PENTAXIM™;|
| Active Comparator: PENTAXIM™ and ENGERIX B® Vaccine Group<br>Participant will receive a booster dose of PENTAXIM™ having received ENGERIX B® and PEDIATRICO in Study A3L02 (Primary series) | Biological: DTaP-IPV//PRP T combined vaccine<br>* 0.5 mL, Intramuscular<br>* Other names: PENTAXIM™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Antibody Persistence at 18 Months of Age in Participants That Received Primary Series Vaccination of Either DTaP-IPV-HepB-PRP T or PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 Months of Age. | Antibody persistence (pre-booster) were defined as titers ≥ 10 mIU/mL for hepatitis B (Hep B;); ≥ 0.15 µg/mL for Haemophilus influenzae type b (PRP); ≥ 0.01 IU/mL for Diphtheria and Tetanus; ≥ 8 (1/dil) for polio types 1, 2, and 3; and ≥ 4 EU/mL for Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA). | Day 0 (Before booster vaccination) | 
| Summary of Booster Response in Participants at 18 Months of Age Following Booster Vaccination With PENTAXIM™ Following a Primary Series Vaccination of Either DTaP-IPV-HepB-PRP T or PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 Months of Age. | Booster response were defined as titers ≥ 1.0 µg/mL for Haemophilus influenzae type b (PRP); ≥ 0.1 IU/mL for Diphtheria and Tetanus; ≥ 8 (1/dil) for Polio types 1, 2, and 3; and for Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA) ≥ 4 EU/mL and a ≥ 4 fold increase from pre-booster to post-booster value. | Day 30 Post-booster Vaccination | 
| Geometric Mean Titers (GMTs) of Antibodies Before and After Booster Vaccination With PENTAXIM™ Following a Primary Series Vaccination of Either DTaP-IPV-HepB-PRP T or PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 Months of Age. | Antibody titers determination: Hepatitis B (Hep B) by enhanced chemiluminescence assay; Haemophilus influenzae type b (PRP), Tetanus, Pertussis toxoid (PT) and filamentous hemagglutinin (FHA) by enzyme linked immunosorbent assay (ELISA); Diphtheria by neutralization test; Poliovirus types 1,2, and 3 by microneutralization assay. | Day 0 (pre-booster) and Day 30 post-booster | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Post-booster Vaccination With PENTAXIM™ | Solicited Injection Site Reactions: Pain, Erythema, Swelling. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability. Grade 3 was defined as: Pain, cries when injected limb is moved or movement of limb is reduced; Erythema and Swelling, ≥ 5 cm; Pyrexia, ≥ 39.6ºC; Vomiting, ≥ 6 episodes/24 hour or requiring parenteral hydration; Crying, > 3 hours; Somnolence, sleeping most of the time or difficulty to wake up; Anorexia, refuses ≥ 3 feeds/meals or refuses most feeds/meals; and Irritability, inconsolable. | Day 0 up to Day 30 post-booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Tetanus, Pertussis, whooping cough, Haemophilus influenzae type b, Hepatitis B, Poliomyelitis