Immunogenicity and Safety of Havrix™ Co-Administered With a Diphtheria, Tetanus and Pertussis and a Haemophilus b Vaccine in Children Aged 15 Months

Study Overview
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Brief Summary
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This is a study to evaluate the immune response and safety of GSK Biologicals 2-dose inactivated hepatitis A vaccine when administered with a diphtheria, tetanus and pertussis combination (DTaP) vaccine and a Haemophilus influenza type B (Hib) vaccine in children 15 months of age. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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An open, controlled comparison of Havrix™ administered alone or with Infanrix™ and ActHIB. The three groups evaluated are: 1) Havrix™ alone, 2) Havrix™ + Infanrix™ and ActHIB and 3) Infanrix™ and ActHIB followed by Havrix™ one month later.

Official Title
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Immunogenicity and Safety of GSK Biologicals' Inactivated Hepatitis A Vaccine (Havrix™) Co-administered With GSK Biologicals' DTaP Vaccine (Infanrix™) and Aventis Pasteur's Haemophilus b Conjugate Vaccine (ActHIB) in Healthy Children 15 Months of Age

Conditions
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Hepatitis A

Intervention / Treatment
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* Biological: Havrix™
* Biological: Infanrix™
* Biological: ActHIB™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects whose parents/guardians are believed by the investigator to be willing to comply with the requirements of the protocol A male or female child 12 or 13 months of age at the time of entry into the Enrolment Phase, Subjects must have previously received three doses each of DTaP and Hib vaccines during the first year of life. The three doses of DTaP vaccine must have been administered as either Infanrix™ or Pediarix™ and the three doses of Hib vaccine must have been administered as ActHIB™, HibTITER™, OmniHIB™. Subjects who, at 15 months of age, will have had at least six months elapse since their third dose of Infanrix™ or Pediarix™, Written informed consent obtained from the parents or guardian of the subject, Free of obvious health problems as established by medical history and history-directed physical examination before entering into the study, and Parents/guardian of the subject must have a telephone or be able to be contacted by telephone. Exclusion Criteria: Use of any investigational or non-registered drug or vaccine other than the study vaccine(s) within 31 days preceding the first dose of study vaccine, or planned use during the study period, Chronic administration (defined as more than 14 days) of immuno-suppressant or other immune-modifying drugs within six months prior to vaccination or planned administration at any time during the study period. Planned administration or administration of any vaccine not foreseen by the study protocol during the period 42 days before and 31 days after each dose of study vaccine(s). Previous vaccination against DTaP using a commercially-available brand other than Infanrix™ or Pediarix™ or against Hib using a commercially-available brand other than ActHIB™, HibTITER™ or OmniHIB™. Previous vaccination with more than three doses of DTaP-containing vaccines or more than three doses of Hib-containing vaccines. Previous vaccination against hepatitis A, History or known exposure to hepatitis A, History of diphtheria, tetanus, pertussis and/or Haemophilus influenza type b, Known exposure to diphtheria, tetanus, pertussis and/or Haemophilus influenza type b within 31 days prior to the start of the study, History of non-response to any vaccine in the current routine immunization schedule, Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, A family history of congenital, hereditary or infectious immunodeficiency or parental risk factors for HIV infection, History of allergic disease/reactions or hypersensitivity likely to be exacerbated by any component of Havrix™, Infanrix™ or ActHIB™ including 2-phenoxyethanol, neomycin and gelatin, History of hypersensitivity/allergic reaction to latex Major congenital defects or serious chronic illness, History of any neurologic disorder Acute disease at the time of vaccination. Administration of immunoglobulins and/or any blood products within three months prior to the first dose of study vaccine or planned administration at any time during the entire study period, i.e., the Enrolment Phase, the Active Phase and the Extended Safety Follow-up Phase

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 13 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 |
| --- | --- |
| Active Comparator: Havrix Group<br>Subjects received one dose of Havrix at Day 0 followed by a second dose of Havrix at Month 6-9. | Biological: Havrix™<br>* 2 intramuscular injections, 6 months apart<br>|
| Experimental: Infanrix + ActHIB→Havrix Group<br>Subjects received Infanrix co-administered with ActHIB at Day 0, followed by one dose of Havix at Day 30 and a second dose of Havrix at Month 7-10. | Biological: Havrix™<br>* 2 intramuscular injections, 6 months apart<br>Biological: Infanrix™<br>* 1 intramuscular injection<br>Biological: ActHIB™<br>* 1 intramuscular injection<br>|
| Active Comparator: Havrix + Infanrix + ActHIB Group<br>Subjects received one dose of Havrix co-administered with Infanrix and ActHIB vaccines at Day 0 followed by a second dose of Havrix at Month 6-9. | Biological: Havrix™<br>* 2 intramuscular injections, 6 months apart<br>Biological: Infanrix™<br>* 1 intramuscular injection<br>Biological: ActHIB™<br>* 1 intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the Second Dose of Havrix | Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 15 milli-International Units per milliliter (mIU/mL). | 31 days following the second dose of Havrix™ | 
| Number of Anti-diphtheria, Anti-tetanus and Anti-polyribosylribitol Phosphate (PRP) Seroprotected Subjects | Subjects are defined as being anti-diphtheria, anti-tetanus and anti-PRP seroprotected if their anti-diphtheria and anti-tetanus antibody concentration is ≥ 0.1 International Units per milliliter (IU/mL) and if their anti-PRP antibody concentration is ≥ 1 microgram per milliliter (μg/mL), respectively. | 31 days following the administration of Infanrix™ and ActHIB | 
| Number of Vaccine Responders for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (PRN) | Subjects are considered as being vaccine responders if they were initially seronegative and become seropositive (≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL)), or were initially seropositive and have a 2-fold increase above pre-study concentrations. | 31 days following the administration of Infanrix™ and ActHIB | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-diphtheria and Anti-tetanus Antibody Geometric Mean Concentrations (GMC) | GMCs are expressed as International Units per milliliter (IU/mL). | 31 days following the administration of Infanrix™ and ActHIB | 
| Anti-polyribosylribitol Phosphate (PRP) Antibody Geometric Mean Concentrations (GMC) | GMCs are expressed as microgram/milliliter (µg/mL). | 31 days following the administration of Infanrix™ and ActHIB | 
| Number of Subjects Seropositive for Anti-pertussis Toxoid (PT), Anti-filamentous Hemagglutinin (FHA), Anti-pertactin (PRN) and Anti-polyribosylribitol Phosphate (PRP) | Seropositivity is defined as antibody concentrations ≥ 5 Enzyme Linked Immunosorbent Assay Units per Milliliter (EL.U/mL) for anti-PT, anti-FHA and anti-PRN antibodies and as antibody concentrations ≥ 0.15 microgram/milliliter (µg/mL) for anti-PRP antibodies. | 31 days following the administration of Infanrix™ and ActHIB | 
| Number of Seropositive Subjects for Anti-hepatitis A Virus (HAV) Antibodies Following the First Dose of Havrix | Subjects are defined as being anti-HAV seropositive if their anti-HAV antibody concentration is ≥ 15 milli-International Units per milliliter (mIU/mL). | 31 days following the first dose of Havrix™ | 
| Anti-hepatitis A Virus (HAV) Antibody Geometric Mean Concentrations (GMC) Following the First Dose of Havrix | Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are expressed as milli-International Units per milliliter (mIU/mL). | 31 days following the first dose of Havrix™ | 
| Anti-hepatitis Virus A (HAV) Antibody Geometric Mean Concentrations (GMC) Following the Second Dose of Havrix | Anti-hepatitis A (HAV) antibody geometric mean concentrations (GMC) are expressed as milli-International Units per milliliter (mIU/mL). | 31 days following the second dose of Havrix™ | 
| Number of Subjects With Vaccine Response to Havrix™. | Vaccine response to Havrix is defined as post-vaccination anti-HAV antibody concentrations ≥ 15 mIU/mL in initially seronegative subjects or a ≥ 2-fold increase above the pre-vaccination anti-HAV antibody concentration in initially seropositive subjects. | 31 days following the second dose | 
| Number of Subjects Reporting Solicited Local Adverse Events (AEs) | Solicited local AEs assessed include pain, redness and swelling. Data across doses are presented in the table. | 4-day period following each dose of study vaccine(s) | 
| Number of Subjects Reporting Solicited General Adverse Events (AEs) | Solicited general AEs assessed include drowsiness, axillary fever ≥ 37.5°C, irritability and loss of appetite. Data across doses are presented in the table. | 4-day period following each dose of study vaccine(s) | 
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | An Adverse Event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | 31-day period following each dose of study vaccine(s) | 
| Number of Subjects Reporting Serious Adverse Events (SAEs), New Chronic Illnesses and Medically Significant Events | Since the related information about medically significant events was not specifically collected and new chronic illnesses were only collected in the extended safety follow-up phase, all unsolicited adverse events (AEs) throughout the study are reported in the table without identifying which event was a medically significant or new chronic illness. | Active Phase and the 6-months Extended Safety Follow-up (ESFU) Phase. | 

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