Comparison of GSKBiologicals' Hib-MenCY-TT Vaccine vs Licensed Hib Conjugate or Meningococcal Vaccine

Haemophilus Influenzae Type b Clinical Trial

Official title:

Evaluate Immuno and Safety of GSKBiologicals' HibMenCYTT vs Licensed Hib Conjugate Vaccine, Each Coadministered With Pediarix® and Prevnar®, in Healthy Infants. An Exploratory Control Group Will Receive Licensed Menomune® at 3 to 5 Years

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00129129
• Other study ID #: 101858
• Secondary ID: 102015
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2004
• Est. completion date: March 29, 2006

Study information

• Verified date: September 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is evaluating the safety and immunogenicity of GSK Biologicals' Hib-MenCY-TT vaccine compared to a control group receiving licensed Hib conjugate vaccine, each administered at 2, 4, and 6 months of age, and compared to licensed meningococcal serogroups A, C, Y, and W-135 polysaccharide vaccine administered at 3 to 5 years of age.

The safety and immunogenicity of a booster dose of Hib-MenCY-TT vaccine will be compared to a booster dose of licensed Hib conjugate vaccine, each administered at 12 to 15 months of age. The group primed with the Hib conjugate vaccine will re-randomized at 12-15 months of age to receive a booster dose of Hib-MenCY-TT or a booster dose of the Hib conjugate vaccine.

Description:

The non-inferiority of the immunogenicity, safety, and antibody persistence of Hib-MenCY-TT vaccine will be compared to ActHIB®, a monovalent Hib conjugate vaccine licensed in the US.

All subjects will be vaccinated at 2, 4, 6, and 12 to 15 months. The immunogenicity of the MenC and MenY antigens will be summarized.

MenC and MenY immunogenicity will be compared to Menomune® (a quadrivalent meningococcal A, C, Y, and W-135 plain polysaccharide vaccine licensed in the US) administered to children 3 to 5 years of age.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 756
• Est. completion date: March 29, 2006
• Est. primary completion date: September 15, 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 15 Months

Eligibility

Inclusion Criteria:

• For Groups A and B

• Subjects for whom the investigator believes that parents/guardians can and will comply with the requirements of the protocol.

• Healthy male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination.

• Written informed consent obtained from the parent or guardian of the subject.

• Free of obvious health problems as established by medical history and clinical examination before entering the study.

• Born after a gestation period between 36 and 42 weeks.

• Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrollment.

• For Group C

• Subjects for whom the investigator believes that parents/guardians can and will comply with the requirements of the protocol.

• Healthy male or female between, and including, 3 and 5 years of age at the time of the first vaccination.

• Written informed consent obtained from the parent or guardian of the subject.

• Free of obvious health problems as established by medical history and clinical examination before entering the study.

Exclusion Criteria:

-For Groups A and B

• 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.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine(s).

• Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, poliovirus, and/or Streptococcus pneumoniae; more than one previous dose of hepatitis B vaccine.

• History of Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, hepatitis B, poliovirus, and/or Streptococcus pneumoniae disease.

• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including dry natural latex rubber.

• Major congenital defects or serious chronic illness.

• History of any neurologic disorders or seizures.

• Acute disease at time of enrollment.

• Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

For Group C

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose.

• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the dose of study vaccine.

• Previous vaccination against Neisseria meningitidis.

• History of Neisseria meningitidis disease.

• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including dry natural latex rubber

• Major congenital defects or serious chronic illness.

• Acute disease at time of enrollment.

• Administration of immunoglobulins and/or any blood products within the 3 months preceding vaccination or planned administration during the study period.

Related Conditions & MeSH terms

• Haemophilus Influenzae Type b
• Neisseria Meningitidis

Intervention

Biological:
• GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccine
Primary phase: 3 IM doses Booster phase: 1 IM dose
• ActHIB
Primary phase: 3 IM doses Booster phase: 1 IM dose
• Pediarix
Primary phase: 3 IM doses
• Prevnar
Primary phase: 3 IM doses Booster phase: 1 IM dose
• Menomune
Primary phase: 1 SC dose

Locations

Country	Name	City	State
United States	GSK Investigational Site	Bardstown	Kentucky
United States	GSK Investigational Site	Beaver Falls	Pennsylvania
United States	GSK Investigational Site	Boardman	Ohio
United States	GSK Investigational Site	Bossier City	Louisiana
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Centennial	Colorado
United States	GSK Investigational Site	Des Moines	Iowa
United States	GSK Investigational Site	Erie	Pennsylvania
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Greenville	Pennsylvania
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	New Bedford	Massachusetts
United States	GSK Investigational Site	Norristown	Pennsylvania
United States	GSK Investigational Site	Norwich	Connecticut
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	Rydal	Pennsylvania
United States	GSK Investigational Site	University Heights	Ohio
United States	GSK Investigational Site	Warwick	Rhode Island

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (4)

Bryant KA, Marshall GS. Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers. Expert Rev Vaccines. 2011 Jul;10(7):941-50. doi: 10.1586/erv.11.90. Review. — View Citation

Marchant CD, Miller JM, Marshall GS, Blatter M, Aris E, Friedland LR, Boutriau D; HibMenCY-TT 005 Study Group. Randomized trial to assess immunogenicity and safety of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in infants. Pediatr Infect Dis J. 2010 Jan;29(1):48-52. doi: 10.1097/INF.0b013e3181c3ce88. — View Citation

Marshall GS, Marchant CD, Blatter M, Aris E, Boutriau D, Poolman JT, Friedland LR, Miller JM. Immune response and one-year antibody persistence after a fourth dose of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY) at 12 to 15 months of age. Pediatr Infect Dis J. 2010 May;29(5):469-71. doi: 10.1097/INF.0b013e3181cdd379. — View Citation

Marshall GS, Marchant CD, Blatter M, Friedland LR, Aris E, Miller JM. Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States. Hum Vaccin. 2011 Feb;7(2):258-64. Epub 2011 Feb 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (=) Cut-off Value.	The anti-PRP antibody cut-off value used for this outcome was 1.0 microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .	One month after the 3-dose primary vaccination course (at Month 5)
Primary	Concentration of Antibodies Against Streptococcus Pneumoniae Serotypes	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL). Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	One month after the 3-dose primary vaccination course (at Month 5)
Primary	Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .	One month after the 3-dose primary vaccination course (at Month 5)
Primary	Number of Subjects Reporting Any Grade 3 Symptoms	"Symptoms" were defined as solicited local and general symptoms and unsolicited adverse events (AEs). A "Grade 3" symptom was defined as any symptom that prevented normal everyday activity. "Any" was defined as an occurrence of any specified symptom regardless of intensity grade. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	During the 4-day follow-up period after each primary vaccine dose
Primary	Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (=) Cut-off Value	The anti-PRP antibody cut-off value used for this outcome was 1.0 microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB/ActHIB groups .	One month after the fourth dose (at Month 11-14)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers = the Cut-off Values	rSBA-MenC antibody cut-off values for this outcome were 1:8 and 1:128.	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers	Titers are presented as geometric mean titers (GMTs).	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers = the Cut-off Values	rSBA-MenY antibody cut-off values for this outcome measure were 1:8 and 1:128.	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers	Titers are presented as geometric mean titers (GMTs).	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers = 1:4	A composite outcome variable was formulated as follows for this immunogenicity analysis outcome: hSBA-Men titers = 1:4 for subjects with post-vaccination rSBA-Men antibody titers = 1:8 and lower than (<) 1:128.	One month after the primary vaccination course (at Month 5 for the MenHibrix and ActHIB groups)/one month after vaccination (at Month 1 for the Menomune Group)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers = 1:4	A composite outcome variable was formulated as follows for this immunogenicity analysis outcome: hSBA-Men titers = 1:4 for subjects with post-vaccination rSBA-Men antibody titers = 1:8 and lower than (<) 1:128.	One month after the primary vaccination course (at Month 5 for the MenHibrix and ActHIB groups)/one month after vaccination (at Month 1 for the Menomune Group)
Secondary	Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Above = the Cut-off Values	Anti-PSC antibody cut-off values for this outcome were 0.3 µg/mL and 2.0 µg/mL.	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Anti-polysaccharide C (Anti-PSC) Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations Equal to or Above = the Cut-off Values	Anti-PSY antibody cut-off values for this outcome were 0.3 µg/mL and 2.0 µg/mL.	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)	Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group)
Secondary	Number of Subjects Reporting Medically Attended Visits	A medically attended visit was defined as an hospitalization, an emergency room visit or a visit to or from medical personnel. This Outcome Measure only concerns subjects in the Menomune Group.	During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0
Secondary	Number of Subjects Reporting Rash	An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae. This Outcome Measure only concerns subjects in the Menomune Group.	During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0
Secondary	Number of Subjects Reporting Serious Adverse Events (SAEs)	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 subject . This Outcome Measure only concerns subjects in the Menomune Group.	During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0
Secondary	Number of Subjects With Anti-PRP Antibody Concentrations = the Cut-off Values	Anti-PRP antibody cut-off values for this outcome were 0.15 µg/mL and 1.0 µg/mL. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Anti-PRP Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations = Cut-off	The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.05 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations = Cut-off	The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.2 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations = Cut-off	The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.5 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentration = 0.1 International Units Per Milliliter (IU/mL)	The anti-diphtheria and anti-tetanus antibody cut-off value for this outcome was = 0.1 IU/mL. This Outcome Measure only concerns the MenHibrix and ActHIB groups.	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Anti-diphtheria and Anti-tetanus Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as international units per milliliter (IU/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Number of Subjects With Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentration = 10.0 Milli-international Units Per Milliliter (mIU/mL)	This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration = 5.0 EL.U/mL	This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Anti PT, Anti-FHA and Anti-PRN Antibody Concentrations	Concentrations of antibodies are presented as GMCs expressed as EL.U/mL. Results for one month after the 3-dose primary vaccination course (at Month 5) are presented under the Primary Outcome Measures section. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to the primary vaccination course (at Day 0)
Secondary	Number of Subjects With Anti-poliovirus Types 1, 2 and 3 Antibody Titer = 1:8	This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Anti-poliovirus Types 1, 2 and 3 Antibody Titers	Titers are presented as geometric mean titers (GMTs). This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)
Secondary	Number of Subjects With Vaccine Response to PT, FHA and PRN	Vaccine response to PT/FHA/PRN was defined as, for initially seronegative subjects, antibody concentration = 5 EL.U/mL one month post-primary vaccination course, and, for initially seropositive subjects, antibody concentration one month post-primary vaccination course = 1-fold the pre-vaccination antibody concentration. A seronegative/seronegative subject was defined as a subject with antibody concentration	One month after the 3-dose primary vaccination course (at Month 5)
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms	Solicited local symptoms were pain, redness and swelling at injection site. "Any" = any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling larger than (>) 10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling > 30 mm. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Within 4 days (Day 0-3) after the 3-dose primary vaccination
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms	Solicited local symptoms were pain, redness and swelling at injection site. "Any" = any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling larger than (>) 10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling > 30 mm. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Within 8 days (Day 0-7) after the 3-dose primary vaccination
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms	Solicited general symptoms were fever, irritability/fussiness, drowsiness, and loss of appetite. "Any" = any report of the specified symptom irrespective of intensity grade and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness and Loss of appetite = symptom that interfered with normal activity; "Grade 3" for Drowsiness and Irritability/Fussiness = symptom that prevented normal activity; "Grade 3" Loss of appetite = not eating at all. Fever = rectal temperature = 38.0 degrees Celsius (°C); "Grade 2 or 3" fever = rectal temperature higher than (>) 39°C; "Grade 3" fever = rectal temperature > 40°C. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	Within 4 days (Day 0-3) after the 3-dose primary vaccination
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms	Solicited general symptoms were fever, irritability/fussiness, drowsiness, and loss of appetite. "Any" = any report of the specified symptom irrespective of intensity grade and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness and Loss of appetite = symptom that interfered with normal activity; "Grade 3" for Drowsiness and Irritability/Fussiness = symptom that prevented normal activity; "Grade 3" Loss of appetite = not eating at all. Fever = rectal temperature = 38.0 degrees Celsius (°C); "Grade 2 or 3" fever = rectal temperature higher than (>) 39°C; "Grade 3" fever = rectal temperature > 40°C. This Outcome Measure only concerns the MenHibrix and ActHIB groups	Within 8 days (Day 0-7) after the 3-dose primary vaccination
Secondary	Number of Subjects Reporting Unsolicited Adverse Events (AEs)	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.	From Dose 1 (at Day 0) through Day 30 following the last vaccine dose administered (Day 30 post Month 4 vaccination for MenHibrix and ActHIB groups, Day 30 post Month 1 for Menomune Group).
Secondary	Number of Subjects Reporting Serious Adverse Events (SAEs)	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.	During the entire Primary Phase of the study, from Day 0 up to the end of Primary Phase safety follow-up period (6 months after the last vaccination).
Secondary	Number of Subjects Reporting Serious Adverse Events (SAEs)	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. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.
Secondary	Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCIs)	NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine
Secondary	Number of Subjects Reporting Rash	An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae. This Outcome Measure only concerns the MenHibrix and ActHIB groups .	From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.
Secondary	Number of Subjects Reporting Emergency Room (ER) Visits or Visits to Physicians' Office, Related or Not to Common Illnesses	Emergency room (ER) visits or physicians office visits assessed were those unrelated to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infections, otitis media, pharyngitis, gastroenteritis. This Outcome Measure only concerns the MenHibrix and ActHIB groups.	From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.
Secondary	Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC and Y)	Fourth dose responses to rSBA-MenC and rSBA-MenY were defined as follows (Definition 1): Initially seronegative subjects (pre-fourth dose antibody titer below cut-off: < 1:8) should have an antibody titer at least four-fold higher than the cut-off, one month after fourth dose (post-fourth dose antibody titer =1:32),; Initially seropositive subjects (pre-fourth dose antibody titer above cut-off: =1:8) should have an antibody titer at least four-fold higher than the pre-fourth dose antibody titer, one month after fourth dose.	One month post fourth dose vaccination (at Month 11-14)
Secondary	Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC and Y)	Fourth dose responses to rSBA-MenC and rSBA-MenY were also assessed using a second definition (Definition 2): Post-fourth dose rSBA antibody titers =1:32 in subjects seronegative at the pre-fourth dose time point (rSBA antibody titers < 1:8),; At least (i.e., greater than or equal to) a 4-fold rise in rSBA antibody titers in subjects with pre-fourth dose antibody titers =1:8 but < 1:128,; At least (i.e., greater than or equal to) a 2-fold rise in rSBA antibody titers in subjects with pre-fourth dose antibody titers =1:128.	One month post fourth dose vaccination (at Month 11-14)
Secondary	Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Human Complement (hSBA-MenC and Y)	Fourth dose responses to hSBA-MenC and hSBA-MenY were defined as follows (Definition 1): Initially seronegative subjects (pre-fourth dose antibody titer below cut-off: < 1:8) should have an antibody titer at least four-fold higher than the cut-off, one month after the fourth dose (post-fourth dose antibody titer =1:16),; Initially seropositive subjects (pre-fourth dose antibody titer above cut-off: =1:8) should have an antibody titer at least four-fold higher than the pre-fourth dose antibody titer, one month after the fourth dose.	One month post fourth dose vaccination (at Month 11-14)
Secondary	Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Human Complement (hSBA-MenC and Y)	Fourth dose responses to hSBA-MenC and hSBA-MenY were also assessed using a second definition (Definition 2): Post-fourth dose hSBA antibody titers =1:16 in subjects seronegative at the pre-fourth dose time point (hSBA antibody titers < 1:8),; At least (i.e., greater than or equal to) a 4-fold rise in hSBA antibody titers in subjects with pre-fourth dose antibody titers =1:4 but < 1: 8,; At least (i.e., greater than or equal to) a 2-fold rise in hSBA antibody titers in subjects with pre-fourth dose antibody titers =1:8.	One month post fourth dose vaccination (at Month 11-14)
Secondary	Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.05 Microgram Per Milliliter (µg/mL)	Streptococcus pneumoniae antibody cut-off values assessed was =0.05 µg/mL for the 7 serotypes in Prevnar vaccine.; Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.	One month after fourth dose vaccination (at Month 11-14)
Secondary	Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.2 Microgram Per Milliliter (µg/mL)	Streptococcus pneumoniae antibody cut-off values assessed was =0.2 µg/mL for the 7 serotypes in Prevnar vaccine.; Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.	One month after fourth dose vaccination (at Month 11-14)
Secondary	Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.5 Microgram Per Milliliter (µg/mL)	Streptococcus pneumoniae antibody cut-off values assessed was =0.5 µg/mL for the 7 serotypes in Prevnar vaccine.; Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.	One month after fourth dose vaccination (at Month 11-14)
Secondary	Concentration of Antibodies Against Streptococcus Pneumonia Serotypes	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).; Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.	One month post fourth dose vaccination (at Month 11-14)
Secondary	Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations Equal to or Above the Cut-off Values	Anti-PRP antibody cut-off values assessed were =0.15 µg/mL and =1.0 µg/mL.	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Anti-PRP Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers Equal to or Above the Cut-off Values	rSBA-MenC antibody cut-off values assessed were =1:8 and =1:128	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	rSBA-MenC Antibody Titers	Titers are presented as geometric mean titers (GMTs).	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers Equal to or Above the Cut-off Values	rSBA-MenY antibody cut-off values assesse were =1:8 and =1:128.	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	rSBA-MenY Antibody Titers	Titers are presented as geometric mean titers (GMTs).	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers Equal to or Above the Cut-off Values	hSBA-MenC antibody cut-off values assessed were =1:4 and =1:8.	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	hSBA-MenC Antibody Titers	Titers are presented as geometric mean titers (GMTs).	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Human Complement (hSBA-MenY) Antibody Titers Equal to or Above the Cut-off Values	hSBA-MenY antibody cut-off values assessed were =1:4 and =1:8.	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	hSBA-MenY Antibody Titers	Titers are presented as geometric mean titers (GMTs).	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Equal to or Above the Cut-off Values	Anti-PSC antibody cut-off values assessed were =0.3 µg/mL and =2.0 µg/mL.	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Anti-PSC Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations Equal to or Above the Cut-off Values	Anti-PSY antibody cut-off values assessed were =0.3 µg/mL and =2.0 µg/mL.	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Anti-PSY Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects With Anti-tetanus Antibody Concentration Equal to or Above 0.1 International Units Per Milliliter (IU/mL)		Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Anti-tetanus Antibody Concentrations	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as international units per milliliter (IU/mL).	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms	Solicited symptoms assessed were pain, redness, swelling at the injection site and increase in limb circumference. "Any"= any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling >10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling >30 mm; "Grade 2" limb circumference (LC) = LC >20 mm; "Grade 3" LC = LC >40 mm	Within 4 days (Day 0-3) after fourth dose vaccination
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms	Solicited symptoms assessed were pain, redness, swelling at the injection site and increase in limb circumference. "Any"= any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling >10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling >30 mm; "Grade 2" limb circumference (LC) = LC >20 mm; "Grade 3" LC = LC >40 mm	Within 8 days (Day 0-7) after fourth dose vaccination
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms	Solicited general symptoms assessed were fever, irritability/fussiness, drowsiness, loss of appetite. "Any"= any report of the specified symptom irrespective of intensity and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness & Loss of appetite = interfered with normal activity; "Grade 3" for Drowsiness, Irritability/Fussiness = prevented normal activity; "Grade 3" Loss of appetite = not eating at all; Fever = rectal temperature (T) =38.0 degrees Celsius (°C); "Grade 2 or 3" for fever = T >39.0°C; "Grade 3" for fever = T >40.0°C	Within 4 days (Day 0-3) after fourth dose vaccination
Secondary	Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms	Solicited general symptoms assessed were fever, irritability/fussiness, drowsiness, loss of appetite. "Any"= any report of the specified symptom irrespective of intensity and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness & Loss of appetite = interfered with normal activity; "Grade 3" for Drowsiness, Irritability/Fussiness = prevented normal activity; "Grade 3" Loss of appetite = not eating at all; Fever = rectal temperature (T) =38.0 degrees Celsius (°C); "Grade 2 or 3" for fever = T >39.0°C; "Grade 3" for fever = T >40.0°C	Within 8 days (Day 0-7) after fourth dose vaccination
Secondary	Number of Subjects Reporting Unsolicited Adverse Events (AEs)	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.	During the 31-day follow-up period following the fourth dose
Secondary	Number of Subjects Reporting New Onset of Chronic Illness(es)	NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.	From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up
Secondary	Number of Subjects Reporting Rash	An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae.	From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up
Secondary	Number of Subjects Reporting Emergency Room (ER) Visits or Physicians Office Visits Related or Not to Common Illnesses	Emergency room (ER) visits or physicians office visits assessed were those unrelated to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infections, otitis media, pharyngitis, gastroenteritis. This Outcome Measure only concerns the MenHibrix and ActHIB groups.	From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up
Secondary	Number of Subjects Reporting Large Swelling Reactions of the Injected Limb(s)	Large injection site reactions were defined as either swelling with a diameter of > 30 mm or a > 30 mm increase in the circumference of the mid-thigh when compared to the baseline (pre-vaccination) measurement, or any diffuse swelling that interfered with or prevented everyday activities (for example, active playing, eating, sleeping).	Within 4 days (Day 0-3) and within 8 days (Day 0-7) following the fourth dose

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