Non-inferiority of GSK Biologicals' DTPw-HBV/Hib Compared to Two Formulations of GSK Biologicals' DTPw-HBV/Hib

Study Overview
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Brief Summary
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The purpose of this observer-blind study is to generate immunogenicity data with one formulation of GSK Biologicals' DTPw-HBV/Hib vaccine after the primary vaccination course and to demonstrate non-inferiority of this vaccine as compared to two formulations of GSK Biologicals' DTPw-HBV/Hib vaccine with respect to the anti-PRP antibody response. Additionally to assess the reactogenicity and safety of GSK Biologicals' DTPw-HBV/Hib vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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Non-inferiority of One Formulation of GSK Biologicals' DTPw-HBV/Hib to 2 Formulations of GSK Biologicals' DTPw-HBV/Hib With Respect to the Immune Response to the PRP Antigen, When Administered to Healthy Infants at 6, 10, 14 Weeks of Age

Conditions
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Tetanus, Whole Cell Pertussis, Haemophilus Influenzae Type b, Diphtheria, Hepatitis B

Intervention / Treatment
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* Biological: Zilbrix-Hib
* Biological: Tritanrix™-HepB/ Hiberix™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. A male or female between, and including, 6 and 8 weeks of age at the time of the first vaccination. Written informed consent obtained from the parent or guardian of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Born after a gestation period of 36 to 42 weeks inclusive. Administration of one dose of hepatitis B vaccine at birth Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period with the exception of OPV. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the administration of the first vaccine dose, (with the exception of OPV). Bacille Calmette-Guérin (BCG) vaccine received after the first 2 weeks of life. Hepatitis B vaccine received after the first week of life. Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae or hepatitis B (except hepatitis B at birth). History of diphtheria, tetanus, pertussis, Haemophilus influenzae or hepatitis B diseases. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Major congenital defects or serious chronic illness. History of any neurologic disorders or seizures. Acute disease at the time of enrolment. Other conditions which in the opinion of the investigator may potentially interfere with interpretation of study outcomes. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 Weeks

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRITANRIX-HEPB/HIBERIX KFT. GROUP<br>Subjects, male or female, aged 6 to 8 weeks received 3 doses of Tritanrix™-HepB/Hiberix™ Kft. vaccine, administered intramuscularly in the anterolateral thigh at 6, 10 and 14 weeks of age. | Biological: Zilbrix-Hib<br>* Intramuscular injection, 1 dose<br>|
| Active Comparator: TRITANRIX-HEPB/HIBERIX LD GROUP<br>Subjects, male or female, aged 6 to 8 weeks received 3 doses of Tritanrix™-HepB/Hiberix™ low-dose (LD) formulation vaccine, administered intramuscularly in the anterolateral thigh at 6, 10 and 14 weeks of age. | Biological: Tritanrix™-HepB/ Hiberix™<br>* Intramuscular injection, 1 dose<br>|
| Active Comparator: TRITANRIX-HEPB/HIBERIX HD GROUP<br>Subjects, male or female, aged 6 to 8 weeks received 3 doses of Tritanrix™-HepB/Hiberix™ high-dose (HD) formulation vaccine, administered intramuscularly in the anterolateral thigh at 6, 10 and 14 weeks of age. | Biological: Tritanrix™-HepB/ Hiberix™<br>* Intramuscular injection, 1 dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigens | A seroprotected subject was defined as a subject with anti-PRP concentrations greater than or equal to (≥) 0.15 microgram per milliliter (µg/mL). | At Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs) | A seroprotected subject is defined as a vaccinated subject with anti-hepatitis B antibody concentration greater than or equal to (≥) 10 milli-international units per milliliter (mIU/mL). | At Month 3 | 
| Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Antigen | A seroprotected subject is defined as a vaccinated subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). Seroprotection was assesed via enzyme-linked immunosorbent assay (ELISA). | At Month 3 | 
| Number of Seroprotected Subjects Against Diphteria (D) With Antibody Concentrations Above the Cut-off | Seroprotection cut-off values assessed were greater than or equal to (≥) 0.016 international units per milliliter (IU/mL) in the sera of subjects seronegative before vaccination. Concentrations were assessed via neutralization assay on Vero cells. | At Month 3 | 
| Number of Seropositive Subjects Against Polyribosyl-ribitol-phosphate (PRP) Antigens | Seropositivity was defined as antibody concentrations greater than or equal to (≥) 1 microgram/milliliter (µg/mL). | At Month 3 | 
| Number of Seropositive Subjects Against Bordetella Pertussis (BPT) Antigen | A seropositive subject was defined as a vaccinated subject with anti-BPT antibody concentration greater than or equal to (≥) 15 ELISA units (EL.U) per milliliter (EL.U/mL). | At Month 3 | 
| Number of Subjects With Vaccine Response to Bordetella Pertussis (BPT) Antigen | Vaccine response was defined as: for initially seronegative subjects, antibody concentration greater than or equal to (≥) 15 EL.U/mL; and for initially seropositive subjects, antibody concentration ≥ 1 fold the pre-vaccination antibody concentration. | At Month 3 | 
| Concentration of Antibodies Against Polyribosyl-ribitol-phosphate (PRP) Antigens | Concentrations are presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (μg/mL). | At Month 3 | 
| Concentration of Antibodies Against Diphtheria (D) and Tetanus (T) Antigens | Concentrations are presented as geometric mean concentrations (GMCs), expressed in international units per milliliter (IU/mL). | At Month 3 | 
| Concentration of Antibodies Against Hepatitis B Surface Antigen (HBs) | Concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL). | At Month 3 | 
| Concentration of Antibodies Against Bordetella Pertussis (BPT) Antigen | Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). | At Month 3 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site. | During the 4-day (Day 0-3) follow-up period post-vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade. Grade 3 Irritability= crying that could not be comforted/prevented normal activity. Grade 3 Drowsiness/Loss of appetite= Drowsiness/Loss of appetite that prevented normal activity. Grade 3 fever = fever above (>) 39.5°C. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-day (Day 0-3) follow-up period post-vaccination | 
| Number of Subjects With Any Unsolicited Adverse Events (AEs) | An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | During the 31-day (Day 0-30) follow-up period post-vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period (Day 0-Month 3) | 

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