Study of the Booster Effect of DTaP-IPV-Hep B-PRP T Combined Vaccine or Infanrix Hexa™ and Prevenar™ in Healthy Infants

Study Overview
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Brief Summary
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This is a follow-up of the primary series vaccination schedule in Study A3L24 (NCT01177722). The objectives are: To describe the antibody persistence to any antigen contained in the investigational DTaP-IPV-Hep B-PRP-T vaccine and Infanrix hexa™ prior to the booster dose To describe the safety and immunogenicity of the booster dose of either DTaP-IPV-Hep B-PRP-T or Infanrix hexa™ vaccine. To describe the immunogenicity of a booster dose of Prevenar™ given at 12 to 24 months.

Detailed Description
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All participants who completed trial A3L24 (NCT01177722) will be recruited to participate in this trial. Those who received DTaP-IPV-Hep B-PRP-T combined vaccine will be randomized to receive either a booster dose of DTaP-IPV-Hep B-PRP-T or Infanrix hexa™ vaccine. Those who received Infanrix hexa™ will receive a booster dose of DTaP-IPV-Hep B-PRP-T combined vaccine. All participants will receive a booster dose of Prevenar™ concomitantly.

Official Title
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Evaluation of Antibody Persistence Following a Primary Series at 2, 4, and 6 Months on Trial A3L24 and Booster Effect of the DTaP-IPV-Hep B-PRP T Combined Vaccine or Infanrix Hexa™ Concomitantly Administered With Prevenar™ at 12 to 24 Months of Age in Healthy Latin American Infants

Conditions
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Tetanus, Diphtheria, Whooping Cough, Hepatitis B, Poliomyelitis

Intervention / Treatment
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* Biological: DTaP-IPV-Hep B-PRP T combined vaccine + Pneumococcal polysaccharide
* Biological: DTaP-Hep B-IPV // Hib Vaccine + Pneumococcal polysaccharide
* Biological: DTaP-IPV-Hep B-PRP T + Pneumococcal polysaccharide vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 12 to 24 months on the day of inclusion. Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by an independent witness(es) if required by local regulations). Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures. Toddlers previously included in Study A3L24 who completed the three-dose primary series vaccination of either DTaP-IPV-Hep B-PRP T or Infanrix hexa™ at 2,4 and 6 months of age according to protocol (both concomitantly administered with Prevenar™ and Rotarix™). Exclusion Criteria: Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the booster vaccinations. Planned participation in another clinical trial during the present trial period. Receipt of any vaccine in the 4 weeks preceding the booster vaccinations, except in case of pandemic influenza vaccination, which may be received at least two weeks before the study vaccines. Planned receipt of any vaccine in the 4 weeks following the trial vaccinations. Previous booster vaccination against pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b, hepatitis B and pneumococcal infection(s) with either the trial vaccine or another vaccine. Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 3 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). Laboratory-confirmed or clinical suspicion of personal or maternal seropositivity for Human Immunodeficiency Virus (HIV), hepatitis B, or hepatitis C, as reported by the parent/guardian. History of pertussis, tetanus, diphtheria, poliomyelitis, Haemophilus influenzae type b, hepatitis B and pneumococcal infection(s), confirmed either clinically, serologically, or microbiologically. At high risk for opportunistic infection during the trial. Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances. History of contraindication to receipt of pertussis-containing vaccine. Laboratory-confirmed or clinical suspicion of thrombocytopenia contraindicating Intramuscular vaccination. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination. History of seizures . Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion. Receipt of oral or injected antibiotic therapy within 72 hours prior to the first blood draw Febrile illness (temperature ≥ 38.0°C) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 24 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group 1<br>Participants previously primed with DTaP-IPV-Hep B-PRP T, will receive one dose of DTaP-IPV-Hep B-PRP T vaccine + one dose of Prevenar™ | Biological: DTaP-IPV-Hep B-PRP T combined vaccine + Pneumococcal polysaccharide<br>* 0.5 mL, Intramuscular each into the right and left deltoid muscle<br>* Other names: Prevenar™;|
| Active Comparator: Study Group 2<br>Participants previously primed with DTaP-IPV-Hep B-PRP T, will receive one dose of Infanrix hexa™ vaccine + one dose of Prevenar™ | Biological: DTaP-Hep B-IPV // Hib Vaccine + Pneumococcal polysaccharide<br>* 0.5 mL, Intramuscular each into the right and left deltoid muscle<br>* Other names: Prevenar™;|
| Experimental: Study Group 3<br>Participants previously primed with Infanrix hexa™ will receive one dose of DTaP-IPV-Hep B-PRP T + one dose of Prevenar™. | Biological: DTaP-IPV-Hep B-PRP T + Pneumococcal polysaccharide vaccine<br>* 0.5 mL (each), Intramuscular each into the right and left deltoid muscle<br>* Other names: Prevenar™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Diphtheria and Tetanus Post Primary Series Antibodies, Persistence and Booster Response Following Vaccination With Either DTaP-IPV Hep B-PRP T Vaccine or Infanrix Hexa Vaccine | Anti-Diphtheria (D) antibodies were measured by a toxin neutralization test. Anti-Tetanus (T) antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Antibody persistence for anti-Diphtheria and anti-Tetanus antibodies was defined as titers ≥0.01 IU/mL and ≥0.1 IU/mL before the booster dose at Day 0. Booster response to Diphtheria and Tetanus was defined as antibody titers ≥0.01 IU/mL and ≥0.1 IU/mL at Day 30 post-booster vaccination. Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers | Day 140 (Primary series) and Day 0 (Pre-booster) | 
| Summary of Pertussis and Filamentous Haemagglutinin Post Primary Series Antibodies, Persistence and Booster Response Following Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine | Anti-Pertussis toxin (PT) and anti-Filamentous haemagglutinin (FHA) antibodies were measured by ELISA. Antibody persistence for anti-PT and anti-FHA was defined as titers ≥ lower limit of quantitation (LLOQ) before the booster dose at Day 0. Booster responses for PT and FHA at Day 30 were defined as: pre-vaccination antibody concentrations < LLOQ and post-vaccination levels ≥ 4 x LLOQ, pre-vaccination antibody concentrations ≥ LLOQ but < 4 x LLOQ and post/pre vaccination ≥ 4, and pre-vaccination antibody concentrations ≥ 4 x LLOQ and post/pre-vaccination ≥ 2. Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers. | Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination | 
| Summary of Polio Antibodies Post Primary Series, Persistence and Booster Response Following Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine | Anti-Poliovirus types 1, 2, and 3 antibodies were measured by neutralization assay. Antibody persistence for anti-Poliovirus 1, 2, and 3 was defined as antibody titers ≥8 (1/dil) before the booster dose at Day 0. Booster response to Poliovirus 1, 2, and 3 was defined as antibody titers ≥8 (1/dil) at Day 30. Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers. | Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination | 
| Summary of Hepatitis B and Haemophilus Influenzae Type B Post Primary Series Antibodies; Antibody Persistence, and Booster Response Following Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine | Anti-Hepatitis B antibodies were measured by the commercially available VITROS ECi/ECiQ Immunodiagnostic System. Anti-Haemophilus influenza type b capsular polyribosyl ribitol phosphate (PRP) antibodies were measured using a Farr type radioimmunoassay that used radiolabeled PRP (3H PRP) in the presence of 36Cl (volume marker). Anti-Hepatitis antibody titers ≥ 10 mIU/mL and ≥ 100 mIU/mL at Day 0 confirmed antibody persistence and booster response at Day 30. Anti-PRP antibody titers ≥ 0.15 µg/ml and ≥ 1.0 µg/ml at Day 0 confirmed antibody persistence and booster response at Day 30. Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers. | Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summary of Geometric Mean Titers to Vaccine Antibodies Post Primary Vaccination Series; Before and After Booster Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine. | Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-Tetanus, anti-PT, and anti-FHA antibodies were measured by ELISA. Anti-Poliovirus types 1, 2, and 3 were measured by neutralization assay. Anti-Hepatitis B antibodies were measured by the commercially available VITROS ECi/ECiQ Immunodiagnostic System. Anti-PRP antibodies were measured using a Farr type radioimmunoassay that used radiolabeled PRP (3H PRP) in the presence of 36Cl (volume marker). Day 140 = Primary series; Day 0 = Pre-booster; and Day 30 = Post-booster titers. | Day 140 after primary vaccination, Day 0 (pre-vaccination), and Day 30 after final booster vaccination | 
| Summary of Immune Response Against Serotypes in the Prevenar Vaccine After Booster Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine | Anti-Streptococcus pneumococcal type specific antibody (anti-Pn PS) was measured by ELISA. Booster response to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F was defined as antibody titers ≥0.35 µg/mL at Day 30. | Day 30 after final booster vaccination | 
| Summary of Geometric Mean Titers to Prevenar Vaccine Antibodies After Booster Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine | Anti-Streptococcus pneumococcal type specific antibody (anti-Pn PS) was measured by ELISA. | Day 30 after final booster vaccination | 
| Summary of Booster Response to Vaccine Antigens Before and After Booster Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine By Age Strata | Anti-PT and anti-FHA antibodies were measured by ELISA. | Day 0 (pre-vaccination) and Day 30 after final booster vaccination | 
| Summary of Geometric Mean Titers to Vaccine Antigens After Booster Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine by Age Strata | Anti-Diphtheria antibodies were measured by a toxin neutralization test. Anti-FHA antibodies were measured by ELISA. Anti-Poliovirus types 1, 2, and 3 were measured by neutralization assay. | Day 30 after final booster vaccination | 
| Number of Participants Reporting a Solicited Injection Site or Systemic Reactions Following Booster Vaccination With Either DTaP-IPV-Hep B-PRP T Vaccine or Infanrix Hexa Vaccine | Solicited injection site: Pain, Erythema, Swelling, and Extensive swelling of vaccinated limb; Solicited systemic reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, and Irritability. Grade 3 Injection site: Pain, Cries if limb is moved or reduced movement; Erythema and Swelling, ≥5 cm; Extensive swelling of limb, Severe. Grade 3 Systemic reactions: Pyrexia (Temperature) >39.5˚C; Vomiting, ≥ 6 times per 24 hours or needing parenteral nutrition; Crying, >3 hours; Somnolence, Sleeping often or difficulty waking; Anorexia, refuses ≥3 meals; and Irritability, Inconsolable. | Day 0 up to Day 7 after final booster vaccination | 
| Number of Participants Reporting a Solicited Injection Site Following Booster Vaccination With Prevenar Vaccine | Solicited injection site: Pain, Erythema, Swelling, and Extensive swelling of vaccinated limb. Grade 3 Injection site: Pain, cries if limb is moved or reduced movement; Erythema and Swelling, ≥5 cm; and Extensive swelling of limb, Severe. | Day 0 up to Day 7 after final booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Tetanus, Whooping Cough, Hepatitis B, Poliomyelitis, Pediatric combined vaccine, Invasive Hib infections