Concomitant Use of Hepatitis A Vaccine, Inactivated With Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) and Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Given to Healthy Children 15 Months of Age (V251-068)

Study Overview
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Brief Summary
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This two-stage study evaluates the immunogenicity, safety, and tolerability of the administration of VAQTA™ (Hepatitis A Vaccine, Inactivated) concomitantly with PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]) and Infanrix™ (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, GlaxoSmithKline) versus the administration of VAQTA™ in healthy children 15 months of age at study entry.

Detailed Description
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In stage I, VAQTA™ given concomitantly with Infanrix™ and/or PedvaxHIB™ was evaluated. In stage 2: Two (2) doses of the VAQTA™ vaccine were administered at least 6 months apart. Safety data was collected after each dose.

Official Title
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An Open, Randomized, Multicenter Study of the Safety, Tolerability, and Immunogenicity of VAQTA™ Given Concomitantly With PedvaxHIB™ and Infanrix™ in Healthy Children 15 Months of Age

Conditions
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Hepatitis A Virus

Intervention / Treatment
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* Biological: Comparator: VAQTA™
* Biological: Comparator: Infanrix™
* Biological: Comparator: PedvaxHIB™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage 1) Healthy males and females 15 months of age with no active liver disease and a negative history of hepatitis A who have been vaccinated against Haemophilus influenzae type b (Hib), diphtheria, tetanus, and pertussis diseases Stage 2) Healthy males and females 12 to 17 months of age with no active liver disease and a negative history of hepatitis A Exclusion Criteria: Stage 1) Males and females previously vaccinated with hepatitis A vaccine, any immune deficiency, a history of allergy to any of the vaccine components, a history of seizure disorder or a neurologic disorder that would contraindicate pertussis vaccine, or a bleeding disorder Stage 2) Males and females previously vaccinated with hepatitis A vaccine, any immune deficiency, a history of allergy to any of the vaccine components, or a history of bleeding disorder

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 17 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: VAQTA™, PedvaxHIB™ and Infanrix™/VAQTA™ (Stage 1)<br>Day 1: VAQTA™ (first dose), PedvaxHIB™ and Infanrix™ were administered concomitantly at different injection sites. Week 24: The second dose of VAQTA™ was administered. | Biological: Comparator: VAQTA™<br>* VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.<br>Biological: Comparator: Infanrix™<br>* Infanrix™ (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, GlaxoSmithKline). One intramuscular 0.5-mL injection of Infanrix™ was administered at the first study visit.<br>Biological: Comparator: PedvaxHIB™<br>* PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.<br>* Other names: visit in all treatment groups in the study.;|
| Experimental: PedvaxHIB™ and Infanrix™/VAQTA™/VAQTA™ (Stage 1)<br>Day 1: PedvaxHIB™ and Infanrix™ were administered concomitantly at different injection sites. Week 4: The first dose of VAQTA™ was administered. Week 28: The second dose of VAQTA™ was administered. | Biological: Comparator: VAQTA™<br>* VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.<br>Biological: Comparator: Infanrix™<br>* Infanrix™ (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, GlaxoSmithKline). One intramuscular 0.5-mL injection of Infanrix™ was administered at the first study visit.<br>Biological: Comparator: PedvaxHIB™<br>* PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.<br>* Other names: visit in all treatment groups in the study.;|
| Experimental: VAQTA™, PedvaxHIB™/VAQTA™ (Stage 1)<br>Day 1: VAQTA™ (first dose) and PedvaxHIB™ were administered concomitantly at different injection sites. Week 24: The second dose of VAQTA™ was administered. | Biological: Comparator: VAQTA™<br>* VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.<br>Biological: Comparator: PedvaxHIB™<br>* PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.<br>* Other names: visit in all treatment groups in the study.;|
| Experimental: PedvaxHIB™/VAQTA™/VAQTA™ (Stage 1)<br>Day 1: PedvaxHIB™ was administered. Week 4: The first dose of VAQTA™ was administered. Week 28: The second dose of VAQTA™ was administered. | Biological: Comparator: VAQTA™<br>* VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.<br>Biological: Comparator: PedvaxHIB™<br>* PedvaxHIB™ (Haemophilus B Conjugate Vaccine [Meningococcal Protein Conjugate]). One intramuscular 0.5-mL injection of PedvaxHIB™ was administered at the first study visit.<br>* Other names: visit in all treatment groups in the study.;|
| Experimental: VAQTA™/VAQTA™ (Stage 2)<br>Day 1: The first dose of VAQTA™ was administered. Week 24: The second dose of VAQTA™ was administered. | Biological: Comparator: VAQTA™<br>* VAQTA™ (Hepatitis A Vaccine, Inactivated). Two intramuscular 0.5-mL doses of VAQTA™ were administered 24 weeks apart, with the second dose being administered prior to 24 months of age.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seropositivity Rate (SPR) to Hepatitis A | SPR is the percent of participants with Hepatitis A antibody titers >= 10 milli-International Units/milliliter (mIU/mL), 4 weeks after dose 2 of VAQTA™ regardless of their initial serostatus. Antibody titers to Hepatitis A virus (HAV) were detected in participants' serum samples using an Enzyme Immunoassay (EIA). | 4 weeks after dose 2 of VAQTA™ | 
| Antibody Response Rate to Haemophilus Influenzae Type b (Hib) | Antibodies to the Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) are assessed in participants serum using radioimmunoassay (RIA). The limit of detection (LOD) for the RIA is 6.60 ng/mL. The antibody response rate is defined as the percentage of participants with anti-PRP titers >1.0 mcg/mL, 4 weeks postvaccination with PedvaxHIB™. | 4 weeks postvaccination with PedvaxHIB™ | 
| Number of Participants With Adverse Events (AE) | Systemic and injection site AEs were collected from participants receiving VAQTA™ concomitantly with Infanrix™ and PedvaxHIB™ or PedvaxHIB™ (Stage I) VAQTA™ non-concomitantly with Infanrix™ and PedvaxHIB™ or PedvaxHIB™ (Stage I) VAQTA™ administered alone (Stage II) Safety data was collected on a standardized Vaccination Report Card (VRC) following each dose. Participants returned the VRC after the safety follow-up period for each dose of VAQTA™. AEs determined by the investigator to be possibly, probably or definitely related to the vaccine are reported as Vaccine-related AE. | Days 1 to 14 after any dose of VAQTA™ for systemic AEs, and Days 1 to 5 after any dose of VAQTA™ for injection-site AEs | 
| Geometric Mean Titers (GMTs) to Antibodies for the Pertussis Toxin (PT), Pertussis Filamentous Hemagglutinin Antibody (FHA), and Pertactin (PRN) Components of Infanrix™ | GMTs for antibodies to PT, FHA, and PRN were measured in serum samples of participants vaccinated with Infanrix™. IgG antibodies to PT were assessed using the anti-pertussis toxin enzyme-linked immunosorbent assay (anti-PT ELISA), with the LOD of 2.4 ELU/mL. IgG antibodies to FHA were assessed using the anti-pertussis filamentous hemagglutinin enzyme-linked immunosorbent assay (anti-FHA ELISA), with the LOD of 2.0 ELU/mL. IgG antibodies to PRN were assessed using the anti-pertussis pertactin enzyme-linked immunosorbent assay (anti-PRN ELISA), with the LOD of 3.3 ELU/mL. | 4 weeks postvaccination with Infanrix™ | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis A virus