3 Formulations of Hib-MenCY-TT Vaccine & 1 Formulation of Hib-MenC-TT Vaccine Compared to Licensed Meningococcal Serogroup C Conjugate Vaccine, Each Administered at 2,3,4 Mths of Age

Phase 2

Completed

Conditions: Haemophilus Influenzae Type b
Neisseria Meningitidis

Interventions: Biological: Hib-MenCY-TT vaccine
Biological: Hib-MenC-TT vaccine
Biological: Menjugate ®
Biological: Infanrix penta ®
Biological: Infanrix hexa ®

Registration Number: NCT00129116

Lead Sponsor: GlaxoSmithKline

Brief Summary: This study evaluated the safety and immunogenicity of 3 formulations of Hib-MenCY-TT vaccine and 1 formulation of Hib-MenC-TT vaccine compared to a control group receiving licensed meningococcal serogroup C conjugate vaccine, each administered at 2, 3, and 4 months of age. Antibody persistence and immune responses to booster vaccinations were additionally assessed at 12 to 18 months of age.

Detailed Description: Primary \& booster vaccination study to evaluate the immuno,reacto \& safety of 3 diff. formulations of GSKBio'combined Haemophilus influenzae typeb-meningococcal serogroups C \& Y-conjugate vaccine \& one formulation of GSKBio' Haemophilus influenzae typeb-meningococcal serogroup C conjugate vaccine each given concomitantly With Infanrix penta (DTaP-IPV-HepB vaccine), vs Meningitec meningococcal SerogroupC conj.vaccine) given concomitantly With Infanrix hexa (DTaP-IPV-HepB-Hib vaccine) in infants according a 2-3-4 mth schedule

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 388

Inclusion Criteria

Healthy infants without major congenital illness, immunosuppression, or chronic disease born at 36 to 42 weeks of gestation, between 6 and 12 weeks of age at enrollment, and vaccinated against hepatitis B at birth.

Exclusion Criteria

Infants should not have received any investigational drug, vaccine, chronic immunosuppressants, or immunoglobulin or blood products.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Menhibrix F3/Infanrix-penta Group	Infanrix penta ®	Subjects received Menhibrix vaccine formulation 3 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menhibrix F2/Infanrix-penta Group	Hib-MenCY-TT vaccine	Subjects received Menhibrix vaccine formulation 2 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menhibrix F2/Infanrix-penta Group	Infanrix penta ®	Subjects received Menhibrix vaccine formulation 2 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menitorix/Infanrix-penta Group	Hib-MenC-TT vaccine	Subjects received Menitorix vaccine and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menitorix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menhibrix F1/Infanrix-penta Group	Infanrix penta ®	Subjects received Menhibrix vaccine formulation 1 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menhibrix F3/Infanrix-penta Group	Hib-MenCY-TT vaccine	Subjects received Menhibrix vaccine formulation 3 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menhibrix F1/Infanrix-penta Group	Hib-MenCY-TT vaccine	Subjects received Menhibrix vaccine formulation 1 and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menhibrix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menjugate/Infanrix-hexa Group	Infanrix hexa ®	Subjects received Menjugate vaccine and Infanrix-hexa vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menjugate and Infanrix-hexa vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menitorix/Infanrix-penta Group	Infanrix penta ®	Subjects received Menitorix vaccine and Infanrix-penta vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menitorix and Infanrix-penta vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.
Menjugate/Infanrix-hexa Group	Menjugate ®	Subjects received Menjugate vaccine and Infanrix-hexa vaccine. Vaccines were administered as a 3-dose primary vaccination course at 2, 3 and 4 months of age (at study Months 0, 1 and 2 of the primary phase). At 12-18 months of age (at study Month 0 of the booster phase), subjects received a booster dose of the two vaccines administered in the primary vaccination course. Menjugate and Infanrix-hexa vaccines were administered intramuscularly in the left and right anterolateral thigh, respectively.

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1 Microgram Per Millilitre (µg/mL).	One month after the booster vaccination (at study Month 1 - booster phase)	Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 1 microgram per millilitre (µg/mL)
Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:8	One month after the booster vaccination (at study Month 1 - booster phase)	rSBA-MenC antibody titre cut-off value assessed was ≥1:8
Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:8	One month after the booster vaccination (at study Month 1 - booster phase)	rSBA-MenY antibody titre cut-off value assessed was ≥1:8

Secondary Outcome Measures

Name	Time	Method
rSBA-MenC Antibody Titres	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Titres are expressed as geometric mean titres (GMTs)
Number of Subjects With Anti-FHA, Anti-PRN and Anti-PT Antibody Concentration Equal to or Above 5 Enzyme-Linked Immunosorbent Assay (ELISA) Units Per Millilitre (EL.U/mL)	Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase)	Anti-FHA, anti-PRN and anti-PT antibody concentration cut-off value assessed was ≥ 5 ELISA units per millilitre.
Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Equal to or Above 2.0 Microgram Per Millilitre (µg/mL)	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Anti-PSC antibody concentration cut-off value assessed was ≥2.0 µg/mL
Anti-diphtheria Antibody Concentrations	One month after the third dose (at study Month 3 - primary phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in IU/mL.
Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations	One month after the third dose (at study Month 3 - primary phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in milli-International Units per millilitre (mIU/mL).
Number of Seroprotected Subjects for Anti-hepatitis B Antibodies	One month after the third dose (at study Month 3 - primary phase)	Seroprotection status is defined as anti-HBs antibody concentrations ≥ 10 mIU/mL
Anti-PRP Antibody Concentrations	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL.
Anti-PSY Antibody Concentrations	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL.
Anti-poliovirus Types 1, 2, 3 Antibody Titres	One month after the third dose (at study Month 3 - primary phase)	Titres are expressed as geometric mean titres (GMTs)
Number of Subjects With Solicited Local Symptoms	During the 8-day (Day 0-7) follow-up period (during the booster phase)	Solicited local symptoms assessed were pain, redness and swelling.
Number of Subjects Reporting Serious Adverse Events (SAEs)	Over the full course of the booster phase (up to study Month 1 - booster phase)	SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.
Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:8	Prior to the booster vaccination (at study Month 0 - booster phase)	rSBA-MenC antibody titre cut-off value assessed was ≥1:8
Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:8	Prior to the booster vaccination (at study Month 0 - booster phase)	rSBA-MenY antibody titre cut-off value assessed was ≥1:8
rSBA-MenY Antibody Titres	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Titres are expressed as geometric mean titres (GMTs)
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1 Microgram Per Millilitre (µg/mL).	Prior to the booster vaccination (at study Month 0 - booster phase)	Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 1 microgram per millilitre (µg/mL)
Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentration Equal to or Above 0.30 Microgram Per Millilitre (µg/mL)	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Anti-PSC antibody concentration cut-off value assessed was ≥0.30 µg/mL
Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentration Equal to or Above 0.30 Microgram Per Millilitre (µg/mL)	Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase)	Anti-PSY antibody concentration cut-off value assessed was ≥0.30 µg/mL
Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 0.15 Microgram Per Millilitre (µg/mL).	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Anti-PRP antibody concentration cut-off value assessed was equal to or above (≥) 0.15 microgram per millilitre (µg/mL)
Anti-PSC Antibody Concentrations	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in µg/mL.
Anti-tetanus Antibody Concentrations	Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in International Units per millilitre (IU/mL).
Number of Subjects With Meningococcal Serogroup C Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenC) Titre Equal to or Above 1:128	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	rSBA-MenC antibody titre cut-off value assessed was ≥1:128
Number of Seroprotected Subjects for Anti-poliovirus Types 1, 2 and 3 Antibodies	One month after the third dose (at study Month 3 - primary phase)	Seroprotection status is defined as anti-polio 1, 2 and 3 antibody titres ≥ 1:8
Anti-filamentous Haemagglutinin (Anti-FHA), Anti-pertactin (Anti-PRN), Anti-pertussis Toxoid (Anti-PT) Antibody Concentrations	Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in Enzyme-Linked Immunosorbent Assay (ELISA) Units per millilitre.
Number of Seroprotected Subjects for Anti-tetanus Antibodies	Prior to the first dose and one month after the third dose (at study Months 0 and 3 - primary phase)	Seroprotection status is defined as anti-tetanus toxoid antibody concentration ≥ 0.1 International Units per millilitre (IU/mL)
Number of Subjects With Meningococcal Serogroup Y Serum Bactericidal Assay Using Rabbit Complement (rSBA-MenY) Titre Equal to or Above 1:128	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	rSBA-MenY antibody titre cut-off value assessed was ≥1:128
Number of Subjects With Anti-tetanus Toxoid (Anti-T) Antibody Concentration Equal to or Above 0.1 International Units Per Millilitre (IU/mL).	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Anti-tetanus toxoid antibody concentration cut-off value assessed was ≥ 0.1 IU/mL
Anti-T Antibody Concentrations	Prior to and one month post booster vaccination (at study Months 0 and 1 - booster phase)	Antibody concentrations are expressed as geometric mean concentrations (GMCs) in International Units per millilitre (IU/mL).
Number of Subjects With Solicited General Symptoms	During the 8-day (Day 0-7) follow-up period (during the booster phase)	Solicited general symptoms assessed were drowsiness, irritability, loss of appetite and fever (fever is defined as rectal temperature ≥ 38.0 degrees Celsius (°C)).
Number of Seroprotected Subjects for Anti-diphtheria Antibodies	One month after the third dose (at study Month 3 - primary phase)	Seroprotection status is defined as anti-diphtheria antibody concentrations ≥ 0.1 IU/mL
Number of Subjects With Vaccine Response to PT, FHA and PRN	One month after the third dose (at study Month 3 - primary phase)	Vaccine response rates are defined as appearance of antibodies in subjects who were initially seronegative (i.e., with concentrations \< cut-off value) or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., with concentrations ≥ cut-off value), taking into consideration the decreasing maternal antibodies.
Number of Subjects With Unsolicited Adverse Events (AEs)	During the 31-day (Day 0-30) follow-up period (during the booster phase)	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.