Immunogenicity and Reactogenicity of a Booster Dose of GSK Bio's DTPa-HBV-IPV/Hib Vaccine

Study Overview
=================
Brief Summary
-----------------
The purpose of this booster study is to evaluate, in subjects primed in the primary study 106786, the persistence, at the time of the booster vaccination, of antibodies elicited by the different formulation of DTPa-HBV-IPV/ Hib vaccine (Infanrix Hexa TM). The study will also evaluate the immune response of these subjects to a DTPa-HBV-IPV/Hib booster. This protocol posting deals with the objectives and outcome measures of the booster phase. The objectives and outcomes measures of the primary phase are presented in a separate protocol posting (NCT = 00376779).

Detailed Description
-----------------
This protocol posting has been updated in order to comply with the FDA AA, Sep 2007.

Official Title
-----------------
Immunogenicity and Reactogenicity of GSK Biologicals' DTPa-HBV-IPV/Hib Vaccine When Given as a Booster Dose

Conditions
-----------------
Acellular Pertussis, Diphtheria, Poliomyelitis, Haemophilus Influenzae Type b, Tetanus, Hepatitis B

Intervention / Treatment
-----------------
* Biological: Infanrix Hexa


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol Subjects must have completed the full three-dose primary vaccination course with one of the formulations of the DTPa-HBV-IPV/Hib vaccine in primary study 106786. A male or female between, and including, 16 and 20 months of age at the time of booster 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. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the booster dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the booster vaccine dose. Participation in another clinical study, between the primary study 106786 and the present booster study, or at any time during the study, in which the subject has been or will be exposed to an investigational or a non-investigational product. Planned administration or administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the administration of the booster dose and ending 30 days after the booster dose. Evidence of previous diphtheria, tetanus, pertussis, polio, hepatitis B and/or Hib booster vaccination or disease since the conclusion visit of study 106786. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on physical examination. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products within the three months preceding the booster dose or planned administration during the study period.

Ages Eligible for Study
-----------------
Minimum Age: 16 Months
Maximum Age: 20 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INFANRIX HEXA PF GROUP<br>Healthy male and female subjects between, and including 16 and 20 months of age at the time of booster vaccination, who were given the preservative-free (PF) formulation of Infanrix Hexa™ in the primary vaccination study 106786, additionally received a single booster dose of Infanrix Hexa™ vaccine, administered intramuscularly into the anterolateral quadrant of the right thigh. | Biological: Infanrix Hexa<br>* Vaccine administered as a booster dose at 16-20 months of age<br>* Other names: GSK Biological's combined DTPa-HBV-IPV/Hib vaccine;|
| Experimental: INFANRIX HEXA PC GROUP<br>Healthy male and female subjects between, and including 16 and 20 months of age at the time of booster vaccination, who were given the preservative-containing (PC) formulation of Infanrix Hexa™ in the primary vaccination study 106786, additionally received a single booster dose of Infanrix Hexa™ vaccine, administered intramuscularly into the anterolateral quadrant of the right thigh. | Biological: Infanrix Hexa<br>* Vaccine administered as a booster dose at 16-20 months of age<br>* Other names: GSK Biological's combined DTPa-HBV-IPV/Hib vaccine;|
| Active Comparator: CONTROL GROUP<br>Healthy male and female subjects between, and including 16 and 20 months of age at the time of booster vaccination, who were given the licensed formulation of Infanrix Hexa™ in the primary vaccination study 106786, additionally received a single booster dose of Infanrix Hexa™ vaccine, administered intramuscularly into the anterolateral quadrant of the right thigh. | Biological: Infanrix Hexa<br>* Vaccine administered as a booster dose at 16-20 months of age<br>* Other names: GSK Biological's combined DTPa-HBV-IPV/Hib vaccine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Toxoids | A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). | Before the booster administration (At Month 0) | 
| Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Toxoids | A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations greater than or equal to (≥) 0.1 IU/mL. | One month after the booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs) | A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 milli international units per milliliter (mIU/mL). Also reported are the number of participants with anti-HBs antibody concentrations ≥ 100 mIU/mL. | Before the booster vaccination (At Month 0) | 
| Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs) | A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL. Also reported are the number of participants with anti-HBs antibody concentrations ≥ 100 mIU/mL. | One month after the booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects Against Poliovirus Type 1, Type 2 and Type 3 | A seroprotected subject was defined as a subject with anti-Polio 1, 2 and 3 antibody titers ≥ the value of 8. | Before the booster vaccination (At Month 0) | 
| Number of Seroprotected Subjects Against Poliovirus Type 1, Type 2 and Type 3 | A seroprotected subject was defined as a subject with anti-Polio 1, 2 and 3 antibody titers ≥ the value of 8. | One month after the booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) | A seroprotected subject was defined as a subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | Before the booster vaccination (At Month 0) | 
| Number of Seroprotected Subjects Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) | A seroprotected subject was defined as a subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 EL.U/mL. | One month after the booster vaccination (At Month 1) | 
| Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) | A seroprotected subject was defined as a subject with anti-PRP antibody concentrations greater than or equal to (≥) 0.15 micrograms per milliliter (µg/mL). Also reported are the number of participants with anti-PRP antibody concentrations ≥ 1.0 µg/mL. | Before the booster vaccination (At Month 0) | 
| Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) | A seroprotected subject was defined as a subject with anti-PRP antibody concentrations ≥ 0.15 µg/mL. Also reported are the number of participants with anti-PRP antibody concentrations ≥ 1.0 µg/mL. | One month after the booster vaccination (At Month 1) | 
| Number of Subjects With a Vaccine Response to PT, FHA and PR | Vaccine response was defined as the appearance of antibodies in subjects who were initially seronegative (S-) [i.e. with concentrations lower than (<) the cut-off value] or at least doubling of pre-vaccination antibody concentrations in subjects who were initially seropositive (S+) [i.e. with concentrations greater than (>) the cut-off value). | One month after the booster vaccination (At Month 1) | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL. | Before the booster vaccination (At Month 0) | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL. | One month after the booster vaccination (At Month 1) | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. | Before the booster vaccination (At Month 0) | 
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. | One month after the booster vaccination (At Month 1) | 
| Anti-HBs Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL. | Before the booster vaccination (At Month 0) | 
| Anti-HBs Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL. | One month after the booster vaccination (At Month 1) | 
| Anti-poliovirus Type 1, Type 2 and Type 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | Before the booster vaccination (At Month 0) | 
| Anti-poliovirus Type 1, Type 2 and Type 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | One month after the booster vaccination (At Month 1) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in micrograms per milliliter (µg/mL). | Before the booster vaccination (At Month 0) | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in µg/mL. | One month after the booster vaccination (At Month 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Diphtheria (D) and Tetanus (T) Toxoids | A seroprotected subject was defined as a subject with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL . | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs) | A seroprotected subject was defined as a subject with anti-HBs antibody concentrations ≥ 10 mIU/mL. Also reported are the number of participants with anti-HBs antibody concentrations ≥ 100 mIU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seroprotected Subjects Against Poliovirus Type 1, Type 2 and Type 3 | A seroprotected subject was defined as a subject with anti-polio 1, 2 and 3 antibody titers ≥ the value of 8. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seroprotected Subjects Against PT, FHA and PRN | A seroprotected subject was defined as a subject with anti-PT, anti-FHA and anti-PRN antibody concentrations ≥ 5 EL.U/mL . | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Seroprotected Subjects Against Polyribosyl-ribitol-phosphate (PRP) | A seroprotected subject was defined as a subject with anti-PRP antibody concentrations ≥ 0.15 μg/mL. Also reported are the number of participants with anti-PRP antibody concentrations ≥ 1.0 µg/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-D and Anti-T Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in IU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-HBs Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in mIU/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-poliovirus Type 1, 2 and 3 Antibody Titers | Antibody titers were presented as geometric mean titers (GMTs). | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Anti-PRP Antibody Concentrations | Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in µg/mL. | Before (Month 0) and one month after (Month 1) the booster vaccination | 
| Number of Subjects With a Vaccine Response to PT, FHA and PR | Vaccine response was defined as the appearance of antibodies in subjects who were initially seronegative (S-) (i.e. with concentrations < cut-off value) or at least doubling of pre-vaccination antibody concentrations in subjects who were initially seropositive (S+) (i.e. with concentrations > cut-off value). | One month after the booster dose (At Month 1) | 
| Number of Subjects With Any Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Days 0-3) follow-up period after the booster vaccination | 
| Number of Subjects With Any Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, fever [defined as rectal temperature equal to or above (≥) 38.0 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. | During the 4-day (Days 0-3) follow-up period after the booster vaccination | 
| Number of Subjects With 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 after the booster vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | Assessed SAEs include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From Month 0 to Month 1, during the entire study period | 
| Number of Subjects Reporting Concomitant Medications |  | During the 4-day (Days 0-3) follow-up period after the booster vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hexavalent vaccine, Booster