Immune Memory of DTPw-HBV/Hib Vaccine Following Primary Vaccination, Immuno & Reacto of a Booster Dose Given in Infants

Study Overview
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Brief Summary
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To assess the immune memory following primary vaccination of DTPw-HBV/Hib vaccine and to assess immunogenicity and reactogenicity of a booster dose given at 15 - 18 months of age.

Detailed Description
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Subjects who received DTPw-HBV/Hib in the primary vaccination without HBV at birth will be randomised (1:3 ratio) to receive either: Plain PRP at 10 months of age followed by DTPw-HBV at 15-18 months of age or DTPw-HBV/Hib at 15-18 months of age. Subjects who received DTPw-HBV + Hib in the primary vaccination without HBV at birth will receive DTPw-HBV + Hib as a booster. Subjects who received DTPw-HBV/Hib in the primary vaccination with HBV at birth will receive DTPw-HBV/Hib vaccine as a booster.

Official Title
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Immune Memory of GSK's DTPw-HBV/Hib Vaccine by Giving Plain PRP Polysaccharide at 10 Mths. Immuno & Reacto of a Booster Dose of DTPw-HBV/Hib or DTPw-HBV or DTPw-HBV+Hib at 15-18 Mths in Infants Previously Primed With DTPw-HBV/Hib

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

Intervention / Treatment
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* Biological: Tritanrix™-HepB/Hiberix™ Kft.
* Biological: Tritanrix™-HepB/Hiberix™
* Biological: Hiberix™
* Biological: Polyribosil-Ribitol-Phosphate (PRP) vaccine
* Biological: Tritanrix™-HepB Kft


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: For subjects receiving Plain PRP followed by DTPw-HBV: Male or female infant, 10 to 11 months of age, who previously completed the three-dose primary vaccination course with the DTPw-HBV/Hib vaccine. For subjects receiving DTPw-HBV/Hib or DTPw-HBV + Hib: Male or female infant, 15-18 months of age, who previously completed the three-dose primary vaccination course with the DTPw-HBV/Hib vaccine. For all subjects: Subjects who the investigator believes that their parent/guardian can and will comply with the requirements of the protocol. Free of obvious health problems as established by medical history and clinical examination Exclusion criteria: Use of any investigational or non-registered product other than the study vaccine(s) within 30 days preceding administration of the study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to administration of the study vaccine. Planned administration/administration of a vaccine not foreseen by the study protocol starting 30 days before and ending 30 days after administration of the study vaccine with the exception of oral polio vaccine.

Ages Eligible for Study
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Minimum Age: 10 Months
Maximum Age: 18 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: Tritanrix-HepB/Hiberix Kft. Mix Group<br>Healthy male and female infants who were primed with Tritanrix™-HepB/Hiberix™ Kft. vaccine, received a booster dose of Tritanrix™-HepB/Hiberix™ Kft. administered intramuscularly into the right upper thigh, at 15-18 months of age. | Biological: Tritanrix™-HepB/Hiberix™ Kft.<br>* GlaxoSmithKline (GSK) Biologicals Korlatolt Felelossegu Tarsasag [Kft] (Limited Company) combined diphtheria (D), tetanus (T), whole cell Bordetella pertussis (Pw), hepatitis B vaccine with new sources of D, T and Pw antigens mixed with Haemophilus influenzae type b (Hib2.5) vaccine.<br>* Other names: DTPw-HBV/Hib Kft;|
| Experimental: Tritanrix-HepB/Hiberix Kft. Ref Group<br>Healthy male and female infants who were primed with Tritanrix™-HepB/Hiberix™ vaccine, received a booster dose of Tritanrix™-HepB/Hiberix™ Kft. administered intramuscularly into the right upper thigh, at 15-18 months of age. | Biological: Tritanrix™-HepB/Hiberix™ Kft.<br>* GlaxoSmithKline (GSK) Biologicals Korlatolt Felelossegu Tarsasag [Kft] (Limited Company) combined diphtheria (D), tetanus (T), whole cell Bordetella pertussis (Pw), hepatitis B vaccine with new sources of D, T and Pw antigens mixed with Haemophilus influenzae type b (Hib2.5) vaccine.<br>* Other names: DTPw-HBV/Hib Kft;Biological: Tritanrix™-HepB/Hiberix™<br>* GSK Biologicals' combined diphtheria, tetanus, whole cell Bordetella pertussis, hepatitis B and Haemophilus Influenzae type b vaccine<br>* Other names: DTPw-HBV/Hib;|
| Experimental: HB Tritanrix-HepB/Hiberix Kft. Mix Group<br>Healthy male and female infants who were primed with Tritanrix™-HepB/Hiberix™ Kft. vaccine (with HepB at birth), received a booster dose of Tritanrix™-HepB/Hiberix™ Kft. administered intramuscularly into the right upper thigh, at 15-18 months of age. | Biological: Tritanrix™-HepB/Hiberix™ Kft.<br>* GlaxoSmithKline (GSK) Biologicals Korlatolt Felelossegu Tarsasag [Kft] (Limited Company) combined diphtheria (D), tetanus (T), whole cell Bordetella pertussis (Pw), hepatitis B vaccine with new sources of D, T and Pw antigens mixed with Haemophilus influenzae type b (Hib2.5) vaccine.<br>* Other names: DTPw-HBV/Hib Kft;|
| Experimental: Tritanrix-HepB Kft.+Hiberix Group<br>Healthy male and female infants who were primed with Tritanrix™-HepB Kft. and Hiberix™ vaccines, were boosted with Tritanrix™-HepB Kft. vaccine administered intramuscularly into the right upper thigh and Hiberix™ vaccine, administered intramuscularly into the left upper thigh, at 15-18 months of age. | Biological: Hiberix™<br>* GSK Biologicals' Haemophilus influenzae type b vaccine<br>Biological: Tritanrix™-HepB Kft<br>* GSK Biologicals Korlatolt Felelossegu Tarsasag [Kft] (Limited Company) combined diphtheria, tetanus, whole cell Bordetella pertussis, hepatitis B vaccine with new sources of D, T and Pw antigens produced at GSK Biologicals Kft., Gödöllö, Hungary.<br>* Other names: DTPw-HBV Kft;|
| Experimental: PRP Tritanrix-HepB Kft. Mix Group<br>Healthy male and female infants who were primed with Tritanrix™-HepB/Hiberix™ Kft. vaccine, received plain Polyribosil-Ribitol-Phosphate (PRP) polysaccharide vaccine administered intramuscularly into the right upper thigh, at 10 months of age, followed by a booster dose of Tritanrix™-HepB Kft. administered intramuscularly into the right upper thigh, at 15-18 months of age. | Biological: Tritanrix™-HepB/Hiberix™ Kft.<br>* GlaxoSmithKline (GSK) Biologicals Korlatolt Felelossegu Tarsasag [Kft] (Limited Company) combined diphtheria (D), tetanus (T), whole cell Bordetella pertussis (Pw), hepatitis B vaccine with new sources of D, T and Pw antigens mixed with Haemophilus influenzae type b (Hib2.5) vaccine.<br>* Other names: DTPw-HBV/Hib Kft;Biological: Polyribosil-Ribitol-Phosphate (PRP) vaccine<br>* plain PRP polysaccharide vaccine<br>Biological: Tritanrix™-HepB Kft<br>* GSK Biologicals Korlatolt Felelossegu Tarsasag [Kft] (Limited Company) combined diphtheria, tetanus, whole cell Bordetella pertussis, hepatitis B vaccine with new sources of D, T and Pw antigens produced at GSK Biologicals Kft., Gödöllö, Hungary.<br>* Other names: DTPw-HBV Kft;|
| Experimental: PRP Tritanrix-HepB Kft. Ref Group<br>Healthy male and female infants who were primed with Tritanrix™-HepB/Hiberix™ vaccine, received plain Polyribosil-Ribitol-Phosphate (PRP) polysaccharide vaccine administered intramuscularly into the right upper thigh, at 10 months of age, followed by a booster dose of Tritanrix™-HepB Kft. administered intramuscularly into the right upper thigh, at 15-18 months of age. | Biological: Tritanrix™-HepB/Hiberix™<br>* GSK Biologicals' combined diphtheria, tetanus, whole cell Bordetella pertussis, hepatitis B and Haemophilus Influenzae type b vaccine<br>* Other names: DTPw-HBV/Hib;Biological: Polyribosil-Ribitol-Phosphate (PRP) vaccine<br>* plain PRP polysaccharide vaccine<br>Biological: Tritanrix™-HepB Kft<br>* GSK Biologicals Korlatolt Felelossegu Tarsasag [Kft] (Limited Company) combined diphtheria, tetanus, whole cell Bordetella pertussis, hepatitis B vaccine with new sources of D, T and Pw antigens produced at GSK Biologicals Kft., Gödöllö, Hungary.<br>* Other names: DTPw-HBV Kft;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL | The number of subjects with anti-PRP antibody concentrations equal to or above (≥) 0.15 μg/mL and ≥ 1.0 μg/mL, at one month after the PRP challenge. | At Month 1, post-PRP challenge | 
| Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL. | The number of subjects with anti-PRP antibody concentrations equal to or above (≥) 0.15 μg/mL and ≥ 1.0 μg/mL, at one month post-booster vaccination. | At Month 1, post-booster vaccination | 
| Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T) | A seroprotected subject was defined as a vaccinated subject, with anti-D and anti-T antibody concentrations equal to or above (≥) 0.1 International Units per milliliter (IU/mL). | At Month 1, post-booster vaccination | 
| Seroprotection Rates for Anti-D Antibodies | The seroprotection rate is defined as the estimated proportion of subjects with protective antibodies as assessed by the Enzyme-Linked Immunosorbent Assay (ELISA) (antibody concentration ≥ 0.1 IU/mL), or by Vero-cell neutralisation assay (antibody concentration ≥ 0.016 IU/mL), for subjects seronegative as assessed by ELISA. | At Month 1, post-booster vaccination | 
| Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs) | A seroprotected subject was defined as a vaccinated subject with an anti-HBs antibody concentration equal to or above (≥) 10 milli International Units per milliliter (mIU/mL). | At Month 1, post-booster vaccination | 
| Number of Seroprotected Subjects Against Bordetella Pertussis (BPT) | A seroprotected subject was defined as a vaccinated subject with an anti-BPT antibody concentration equal to or above (≥) 15 ELISA units per milliliter (EL.U/mL). | At Month 1, post-booster vaccination | 
| Number of Subjects With Booster Response to BPT Antigen | The booster response was defined as: an anti-BPT antibody concentration equal to or above (≥) the cut-off value (15 EL.U/mL) at post-booster vaccination in subjects seronegative (anti-BPT antibody concentration < 15 EL.U/mL) prior to administration of the booster dose; or at least a 2-fold increase in antibody concentration from pre- to post-vaccination time points, in subjects who were seropositive (anti-BPT antibody concentration ≥ 15 EL.U/mL) prior to the administration of the booster dose. | At Month 1, post-booster vaccination | 
| Anti-PRP Antibody Concentrations | Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA. | At Month 1, post-PRP challenge | 
| Anti-PRP Antibody Concentrations. | Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA. | At Month 1, post-booster vaccination | 
| Anti-D and Anti-T Antibody Concentrations | Anti-D and anti-T antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in International Units per milliliter (IU/mL), as assessed by ELISA. | At Month 1, post-booster vaccination | 
| Anti-HBs Antibody Concentrations | Anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL), as assessed by ELISA. | At Month 1, post-booster vaccination | 
| Anti-BPT Antibody Concentrations | Anti-BPT antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL), as assessed by ELISA. | At Month 1, post-booster vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL | The number of subjects with anti-PRP antibody concentrations equal to or above (≥) 0.15 μg/mL and ≥ 1.0 μg/mL, prior to the PRP challenge. | At Month 0, prior to the PRP challenge | 
| Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL. | The number of subjects with anti-PRP antibody concentrations equal to or above (≥) 0.15 μg/mL and ≥ 1.0 μg/mL, prior to the booster vaccination. | At Month 0, prior to the PRP challenge | 
| Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ the Cut-off Value | The number of subjects with anti-D antibody concentrations equal to or above (≥) the cut-off value of 0.1 IU/mL as assessed by ELISA, (or ≥ 0.016 IU/mL as assessed by the neutralisation assay on Vero cells in subjects seronegative by ELISA testing) and, the number of subjects with anti-T antibody concentrations ≥ the cut-off value of 0.1 IU/mL as assessed by ELISA. | At Month 0, prior to the PRP challenge | 
| Seroprotection Rates for Anti-D Antibodies | The seroprotection rate is defined as the estimated proportion of subjects with protective antibodies as assessed by ELISA (antibody concentration ≥ 0.1 IU/mL), or by Vero-cell neutralisation assay (antibody concentration ≥ 0.016 IU/mL), for subjects seronegative as assessed by ELISA. | At Month 0, prior to the PRP challenge | 
| Number of Subjects With Anti-HBs Antibody Concentrations ≥ the Cut-off Value | The number of subjects with anti-HBs antibody concentrations equal to or above (≥) the cut-off value of 10 mIU/mL, prior to the booster vaccination. | At Month 0, prior to the PRP challenge | 
| Number of Subjects With Anti-BPT Antibody Concentrations ≥ the Cut-off Value | The number of subjects with anti-BPT antibody concentrations equal to or above (≥) the cut-off value of 15 EL.U/mL, prior to the booster vaccination. | At Month 0, prior to the PRP challenge | 
| Anti- PRP Antibody Concentrations | Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA. | At Month 0, prior to the PRP challenge | 
| Anti- PRP Antibody Concentrations. | Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA. | At Month 0, prior to the PRP challenge | 
| Anti-D and Anti-T Antibody Concentrations. | Anti-D and anti-T antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in International Units per milliliter (IU/mL), as assessed by ELISA. | At Month 0, prior to the PRP challenge | 
| Anti-HBs Antibody Concentrations. | Anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL), as assessed by ELISA. | At Month 0, prior to the PRP challenge | 
| Anti-BPT Antibody Concentrations. | Anti-BPT antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL), as assessed by ELISA. | At Month 0, prior to the PRP challenge | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the 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 (Days 0-3) post-PRP challenge | 
| 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 the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Grade 3 irritability = crying that could not be comforted and prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-Day (Days 0-3) post-PRP challenge | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms. | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the 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 (Days 0-3) post-booster vaccination period | 
| 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 the symptom regardless of intensity grade. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Grade 3 irritability = crying that could not be comforted and prevented normal activity. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination. | During the 4-Day (Days 0-3) post-booster vaccination period | 
| 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 | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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 (from Month 0 to Month 9.5) |