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

Phase 3

Completed

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

Registration Number: NCT00169442

Lead Sponsor: GlaxoSmithKline

Brief Summary: 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: * 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 745

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL.	At Month 1, post-booster vaccination	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.
Number of Seroprotected Subjects Against Diphteria (D) and Tetanus (T)	At Month 1, post-booster vaccination	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).
Number of Seroprotected Subjects Against Hepatitis B Surface Antigen (HBs)	At Month 1, post-booster vaccination	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).
Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL	At Month 1, post-PRP challenge	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.
Seroprotection Rates for Anti-D Antibodies	At Month 1, post-booster vaccination	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.
Number of Seroprotected Subjects Against Bordetella Pertussis (BPT)	At Month 1, post-booster vaccination	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).
Number of Subjects With Booster Response to BPT Antigen	At Month 1, post-booster vaccination	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.
Anti-PRP Antibody Concentrations	At Month 1, post-PRP challenge	Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA.
Anti-PRP Antibody Concentrations.	At Month 1, post-booster vaccination	Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA.
Anti-D and Anti-T Antibody Concentrations	At Month 1, post-booster vaccination	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.
Anti-HBs Antibody Concentrations	At Month 1, post-booster vaccination	Anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL), as assessed by ELISA.
Anti-BPT Antibody Concentrations	At Month 1, post-booster vaccination	Anti-BPT antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL), as assessed by ELISA.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL	At Month 0, prior to the PRP challenge	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.
Number of Subjects With Anti-PRP Antibody Concentrations ≥ 0.15 μg/mL and ≥ 1.0 μg/mL.	At Month 0, prior to the PRP challenge	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.
Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ the Cut-off Value	At Month 0, prior to the PRP challenge	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.
Number of Subjects With Anti-HBs Antibody Concentrations ≥ the Cut-off Value	At Month 0, prior to the PRP challenge	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.
Anti- PRP Antibody Concentrations	At Month 0, prior to the PRP challenge	Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	During the 4-Day (Days 0-3) post-PRP challenge	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.
Seroprotection Rates for Anti-D Antibodies	At Month 0, prior to the PRP challenge	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.
Number of Subjects With Anti-BPT Antibody Concentrations ≥ the Cut-off Value	At Month 0, prior to the PRP challenge	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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	During the 4-Day (Days 0-3) post-PRP challenge	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.
Anti- PRP Antibody Concentrations.	At Month 0, prior to the PRP challenge	Anti-PRP antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in microgram per milliliter (μg/mL), as assessed by ELISA.
Anti-D and Anti-T Antibody Concentrations.	At Month 0, prior to the PRP challenge	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.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms.	During the 4-Day (Days 0-3) post-booster vaccination period	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.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.	During the 4-Day (Days 0-3) post-booster vaccination period	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.
Number of Subjects With Unsolicited Adverse Events (AEs)	During the 31-Day (Day 0-30) follow-up period	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.
Number of Subjects With Serious Adverse Events (SAEs)	During the entire study period (from Month 0 to Month 9.5)	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Anti-HBs Antibody Concentrations.	At Month 0, prior to the PRP challenge	Anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL), as assessed by ELISA.
Anti-BPT Antibody Concentrations.	At Month 0, prior to the PRP challenge	Anti-BPT antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL), as assessed by ELISA.