Study of the DTaP-IPV-Hep B-PRP T Combined Vaccine Following a Primary Series of DTacP IPV-HepB-PRP-T or Infanrix Hexa™

Study Overview
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Brief Summary
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This is a follow-up of Study A3L11 (NCT00404651). Immunogenicity To describe the antibody persistence following a primary series vaccination of either DTaP-IPV-Hep B-PRP T or Infanrix hexa™. To describe the immunogenicity of a booster dose of DTaP-IPV-HepB-PRP T in a subset of subjects. Safety - To describe the safety profile after a booster dose of DTacP-IPV-HepB-PRP T.

Official Title
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Immunogenicity Study of the Antibody Persistence and Booster Effect of the DTaP-IPV-Hep B-PRP T Combined Vaccine at 15 to 18 Months of Age Following a Primary Series of DTaP-IPV-Hep B-PRP T or Infanrix Hexa™ Administered at 2, 4, and 6 Months of Age in Healthy Mexican Infants

Conditions
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Diphtheria, Tetanus, Pertussis, Hepatitis B, Poliomyelitis, Haemophilus Influenzae Type B Infection

Intervention / Treatment
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* Biological: DTaP-IPV-Hep B-PRP T vaccine (Batch 1)
* Biological: DTaP-IPV-Hep B-PRP T vaccine (Batch 2)
* Biological: DTaP-IPV-Hep B-PRP T vaccine (Batch 3)
* Biological: Infanrix Hexa™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Toddlers previously included in Study A3L11 (NCT00404651) who completed the three-dose primary series vaccination of either DTaP-IPV-HepB-PRP-T or Infanrix hexa™ at 2, 4 and 6 months of age Toddlers of 15 to 18 months (456 to 578 days) of age, inclusive Informed Consent Form signed by at least one parent or legal representative and two mandatory witnesses 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 booster vaccination. Planned participation in another clinical trial during the present trial period. Congenital or acquired immunodeficiency, immunosuppressive therapy such as long-term systemic corticosteroid 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 3 months. Any vaccination in the 4 weeks preceding the booster vaccination. Any vaccination planned until the next visit. History of documented pertussis, tetanus, diphtheria, polio, Haemophilus influenzae type b or hepatitis B (HB) infection(s) (confirmed either clinically, serologically or microbiologically). Administration of a vaccine against pertussis, tetanus, diphtheria, polio, Hib, and/or hepatitis B infection(s) since the end of participation in Study A3L11. Coagulopathy, thrombocytopenia or a bleeding disorder contraindicating intramuscular vaccination. Known maternal history of human immunodeficiency virus (HIV), Hepatitis B surface antigen (HbsAg) or Hepatitis C seropositivity. Subjects with any related serious adverse event that occurred following the three-dose primary series administration of the investigational vaccine or of the reference vaccine in Study A3L11. History of seizures. Febrile (temperature ≥38.0°C) or acute illness on the day of inclusion Known contraindication to further vaccination with a pertussis vaccine, i.e.: Encephalopathy; Temperature >40.0°C within 48 hours following a vaccine injection, not due to another identifiable cause during the primary series; Inconsolable crying that occurred for >3 hours within 48 hours following vaccine injection during the primary series; Hypotonic hyporesponsive episode within 48 hours following vaccine injection during the primary series; Seizures with or without fever within 3 days following vaccine injection.

Ages Eligible for Study
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Minimum Age: 15 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: DTaP-IPV-Hep B-PRP T Batch 1<br>Participants had received 3 primary doses of Batch 1 of Diphtheria (D), Tetanus (T), Pertussis (acellular, component [aP]), Hepatitis B (Hep B, [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP T) in Study A3L11 (NCT00404651); and will receive a booster dose of (DTaP-IPV-Hep B-PRP T) at Day 0 in the present study. | Biological: DTaP-IPV-Hep B-PRP T vaccine (Batch 1)<br>* 0.5 mL, Intramuscular<br>|
| Experimental: DTaP-IPV-Hep B-PRP T Batch 2<br>Participants had received 3 primary doses of Batch 1 of Diphtheria (D), Tetanus (T), Pertussis (acellular, component [aP]), Hepatitis B (Hep B, [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP T) in Study A3L11 (NCT00404651) and will receive a booster dose of (DTaP-IPV-Hep B-PRP T) at Day 0 in the present study. | Biological: DTaP-IPV-Hep B-PRP T vaccine (Batch 2)<br>* 0.5 mL, Intramuscular<br>|
| Experimental: DTaP-IPV-Hep B-PRP T Batch 3<br>Participants had received 3 primary doses of Batch 1 of Diphtheria (D), Tetanus (T), Pertussis (acellular, component [aP]), Hepatitis B (Hep B, [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-Hep B-PRP T) in Study A3L11 (NCT00404651) and will receive a booster dose of (DTaP-IPV-Hep B-PRP T) at Day 0 in the present study. | Biological: DTaP-IPV-Hep B-PRP T vaccine (Batch 3)<br>* 0.5 mL, Intramuscular<br>|
| Active Comparator: Infanrix Hexa™<br>Participants had received 3 primary doses of Diphtheria (D), Tetanus (T), Pertussis (acellular, component [aP]), Hepatitis B (Hep B, [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), (Infanrix Hexa™) plus Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed in Study A3L11 (NCT00404651) and received a booster dose of (DTaP-IPV-Hep B-PRP T) at Day 0 in the present study. | Biological: Infanrix Hexa™<br>* 0.5 mL, Intramuscular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers of Antibodies Before and After Booster Vaccination With DTaP-IPV-Hep B-PRP T | Antibody titers were measured for hepatitis B (Hep B) by enhanced chemiluminescence detection, for Haemophilus influenzae type b (PRP) by Farr type radioimmunoassay, for diphtheria by toxin neutralization test, and for tetanus by enzyme linked immunosorbent assay (ELISA). Antibody titers were measured for poliovirus types 1, 2, and 3 by neutralization assay. Antibody titers were measured for pertussis toxoid (PT) and filamentous hemagglutinin (FHA) by ELISA. | Day 0 (pre-booster) and Day 30 (one month post-booster) | 
| Number of Participants With Antibody Persistence Before and Immunogenicity Response After Booster Vaccination With DTaP-IPV-Hep B-PRP T Vaccine | Antibody persistence and immunogenicity response: Level 1: ≥ 10 mIU/mL for hepatitis B (Hep B), ≥ 0.15 µg/mL for Haemophilus influenzae type b (PRP), and ≥ 0.01 IU/mL for diphtheria (D) and tetanus (T). Level 2: ≥ 100 mIU/mL (Hep B), ≥ 1.0 µg/mL (PRP), and ≥ 0.1 IU/mL (D and T) Level 3, ≥ 1.0 IU/mL (D and T). Anti-polio titers were defined as ≥ 8 (1.dil), and pertussis toxoid (PT) and filamentous hemagglutinin (FHA) by a 4 fold increase from Day 0. | Day 0 (pre-booster) and Day 30 (one month post-booster) | 
| Number of Participants With Solicited Injection Site or Systemic Reactions After Vaccination With DTaP-IPV-Hep B-PRP T Vaccine | Solicited Injection Site Reactions: Pain, Erythema, Swelling, Extensive Swelling of Vaccinated Limb. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability. Grade 3 reactions were defined as: Pain, cries when injected limb is moved or movement of injected limb reduced; Erythema and swelling, ≥ 5cm; Extensive swelling of limb; Pyrexia, ≥ 39.6ºC; Vomiting ≥ 6 episodes/24 hours or requiring parenteral hydration; Somnolence, sleeping most of time or difficult to wake up; Anorexia, refuses ≥ feeds or most feeds; Irritability, inconsolable. | Days 0 up to 7 after any injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Tetanus, Pertussis, Hepatitis B, Poliomyelitis, Invasive Haemophilus influenzae type b., Haemophilus Influenzae Type B Infection