Safety and Immunogenicity Study of Hib-MenCY-TT Vaccine Compared to Licensed Hib Conjugate Vaccine

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00289783
• Collaborator: (none)
• Enrollment: 4,441
• Locations: 93
• Arms: 5
• Duration (Months): 24.1
• Patients Per Site: 47.8
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This study evaluates the immunogenicity and consistency of 3 Hib-MenCY-TT vaccine lots and the safety and immunogenicity of Hib-MenCY-TT vaccine compared to a control group receiving licensed Hib conjugate vaccine, when each are co-administered with Pediarix® to healthy infants at 2, 4, and 6 months of age. The study will also evaluate the safety and immunogenicity of Hib-MenCY-TT vaccine compared to a control group receiving licensed Hib conjugate vaccine, when each are co-administered with M-M-R® II and Varivax® at 12 to 15 months of age.

Condition or Disease	Intervention/Treatment	Phase
Haemophilus Influenzae Type b; Neisseria Meningitidis	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine; Biological: ActHIB; Biological: PedvaxHIB; Biological: Pediarix; Biological: Prevnar; Biological: M-M-R II; Biological: Varivax	Phase 3

Detailed Description

The subjects from this study will participate in one of three cohorts:

• US Safety and Immunogenicity (Cohort 1): All immunogenicity analyses in the primary and booster phases will be evaluated in this cohort. These subjects will also contribute to the safety analyses in the primary and booster phases.

• Safety Only (Cohort 2): Only safety objectives will be assessed in the primary and booster phases for this cohort.

• Non-US Safety and Immunogenicity (Cohort 3): Only descriptive immunogenicity results in the primary and booster phases will be reported for this cohort. These subjects will also contribute to the safety analyses in the primary and booster phases.

Treatment allocation:

Primary phase: Subjects will be randomized with balanced allocation (1:1:1:1) to 1 of the 4 treatment groups and with a stratification according to the cohort. Assignment to a cohort will be based on study site.

Booster phase: Subjects who received Hib-MenCY-TT vaccine in the primary phase will receive a booster dose of Hib-MenCY-TT vaccine. Subjects who received ActHIB in the primary phase will receive a booster dose of PedvaxHIB.

During the 3-dose primary vaccination course, co-administration of Prevnar, Synagis, and/or rotavirus vaccine is permitted; co-administration of influenza vaccine is permitted at dose 3.

During the booster vaccination, co-administration of Prevnar, hepatitis A vaccine and influenza vaccine is permitted for all subjects in Cohort 1, 2 and 3; and co-administration of measles, mumps, rubella and varicella vaccine is permitted for all subjects in Cohort 2 and 3.

The study will be conducted in a double-blind fashion with regard to consistency of the 3 manufacturing lots of Hib-MenCY-TT vaccine and single-blind fashion for Hib-MenCY-TT vaccine versus monovalent Hib vaccine. The parents/guardians will be blinded up to collection of all data pertaining to the period up to one month after booster vaccination. Therefore, the extended safety follow-up after the booster dose will be conducted in an unblinded manner. The person administering the vaccines will ensure that the parent/guardian does not see the vaccine vial used in reconstituting the vaccine. Due to the differences in the presentations of the candidate Hib-MenCY-TT vaccine and control vaccines, it is not possible to blind study personnel who administer the vaccines.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4441 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase III, Randomized, Multinational Study, Double-blinded for the Immunogenicity and Consistency Evaluation of 3 Hib-MenCY-TT Vaccine Lots and Single-blinded and Controlled for the Evaluation of Safety and Immunogenicity of GSK Biologicals' Haemophilus Influenzae Type b and Neisseria Meningitidis Serogroups C and Y-tetanus Toxoid Conjugate Vaccine Combined (Hib-MenCY-TT) Compared to Monovalent Hib Vaccine in Healthy Infants at 2, 4, 6, and 12 to 15 Months of Age.
• Study Start Date: Feb 22, 2006
• Actual Primary Completion Date: Aug 27, 2007
• Actual Study Completion Date: Feb 26, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Menhibrix A Group Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: Pediarix; 3-dose intramuscular injection at 2, 4 and 6 months of age.; Other Names: Infanrix penta ; Biological: Prevnar; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: M-M-R II; 1 booster dose by subcutaneous injection at 12 to 15 months of age.; Biological: Varivax; 1 booster dose by subcutaneous injection at 12 to 15 months of age
Experimental: Menhibrix B Group Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: Pediarix; 3-dose intramuscular injection at 2, 4 and 6 months of age.; Other Names: Infanrix penta ; Biological: Prevnar; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: M-M-R II; 1 booster dose by subcutaneous injection at 12 to 15 months of age.; Biological: Varivax; 1 booster dose by subcutaneous injection at 12 to 15 months of age
Experimental: Menhibrix C Group Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: Pediarix; 3-dose intramuscular injection at 2, 4 and 6 months of age.; Other Names: Infanrix penta ; Biological: Prevnar; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: M-M-R II; 1 booster dose by subcutaneous injection at 12 to 15 months of age.; Biological: Varivax; 1 booster dose by subcutaneous injection at 12 to 15 months of age
Experimental: Menhibrix Group Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Biological: GSK Biologicals' Haemophilus influenzae type b and Neisseria meningitidis 792014 vaccine; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: Pediarix; 3-dose intramuscular injection at 2, 4 and 6 months of age.; Other Names: Infanrix penta ; Biological: Prevnar; 3-dose intramuscular injection at 2, 4 and 6 months of age, and 1 booster dose by intramuscular injection at 12 to 15 months of age.; Biological: M-M-R II; 1 booster dose by subcutaneous injection at 12 to 15 months of age.; Biological: Varivax; 1 booster dose by subcutaneous injection at 12 to 15 months of age
Active Comparator: ActHIB Group Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Biological: ActHIB; 3-dose intramuscular injection at 2, 4 and 6 months of age.; Biological: PedvaxHIB; 1 booster dose by intramuscular injection at 12 to 15 months of age.

Outcome Measures

Primary Outcome Measures

1. Anti-Polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations [One month after primary vaccination]

   Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

2. Neisseria Meningitidis Serogroup C (MenC) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers [One month after primary vaccination]

   Titers were expressed as Geometric Mean Titers (GMTs) This analysis occured on the cohort 1 : Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

3. Neisseria Meningitidis Serogroup Y (MenY) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers [One month after primary vaccination]

   Titers are expressen as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

4. hSBA-MenC Antibody Titers [Prior to the fourth dose vaccination and 42 days after the fourth dose]

   Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

5. hSBA-MenY Antibody Titers [Prior to the fourth dose vaccination and 42 days after the fourth dose]

   Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

6. Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL) [One month after primary vaccination]

   This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

7. Number of Subjects With hSBA-MenC Titer Equal to or Above 1:8 [42 days after the fourth dose]

   This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

8. Number of Subjects With hSBA-MenY Titer Equal to or Above 1:8 [42 days after the fourth dose]

   This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

9. Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 150 Milli-international Units Per Milli-liter (mIU/ML) [42 days after the fourth dose]

   The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 150 mIU/mL. Co-administration with MMR-II vaccine

10. Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter [42 days after the fourth dose]

    This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

11. Number of Subjects With Anti-mumps Titer Equal to or Above 28 Estimated Dose 50 (ED50) [42 days after the fourth dose]

    The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-mumps antibody titers below 28 ED50 Co-administration with MMR-II vaccine.

12. Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 10 International Units Per Milli-litre (IU/mL) [42 days after the fourth dose]

    The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 4 IU/mL. Co-administration with MMR-II vaccine.

13. Number of Subjects With Anti-varicella Titer Equal to or Above 1:5 [42 days after the fourth dose]

    The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody titer below 1:5. Co-administration with Varivax vaccine.

Secondary Outcome Measures

1. Number of Subjects With Anti-tetanus (Anti-T) and Anti-diphtheria Toxoid (Anti-D) Antibody Concentrations Equal to or Above 0.1 International Units Per Millilitre (IU/mL) [One month after primary vaccination]

   This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

2. Anti-D and Anti-T Antibody Concentrations [One month after primary vaccination]

   Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in international units per milliliter (IU/mL). This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

3. Number of Subjects With Anti Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above 10.0 Milli-international Units Per Millilitre (mIU/mL) [One month after primary vaccination]

   Results are stratified by the presence or absence of a birth dose of hepatitis B vaccine. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

4. Anti-HBS Antibody Concentrations [One month after primary vaccination]

   Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in milli-International units per milliliter (mIU/mL) Results are stratified by the presence or absence of a birth dose of hepatitis B vaccine. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

5. Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations Equal to or Above 5 ELISA Units Per Millilitre (EL.U/mL) [One month after primary vaccination]

   This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

6. Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations [One month after primary vaccination]

   This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

7. Number of Subjects With Anti-poliovirus Types 1, 2 and 3 Equal to or Above 8 Estimated Dose 50 (ED50) [One month after primary vaccination]

   This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

8. Anti-poliovirus Types 1, 2 and 3 Titers [One month after primary vaccination]

   Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

9. Number of Subjects With Antibodies to Neisseria Meningitidis Serogroup C and Y Polysaccharide Capsule (Anti-PSC and Anti-PSY) Concentrations Equal to or Above the Cut-off Values [One month after primary vaccination]

   Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 microgram per milliliter (µg/mL) and >=2.0 µg/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

10. Anti-PSC and Anti-PSY Antibody Concentrations [One month after primary vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per milliliter (µg/mL) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

11. Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Values [One month after the primary vaccination course]

    Anti-PRP antibody cut-off values assessed were >=0.15 microgram per milliliter (µg/mL) and >=1.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

12. Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Values [Prior to the fourth dose vaccination and one month after fourth dose vaccination]

    Anti-PRP antibody cut-off values assessed were >=0.15 microgram per milliliter (µg/mL) and >=1.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

13. Anti-PRP Antibody Concentrations [One month after the primary vaccination course]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

14. Anti-PRP Antibody Concentrations [Prior to the fourth dose vaccination and one month after fourth dose vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

15. Number of Subjects With hSBA-MenC and hSBA-MenY Titers Equal to or Above the Cut-off Values [One month after the primary vaccination course]

    hSBA-MenC/Y antibody cut-off values assessed were >=1:4 and >=1:8 The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

16. Number of Subjects With hSBA-MenC and hSBA-MenY Titers Equal to or Above the Cut-off Values [Prior to the fourth dose vaccination and one month after fourth dose vaccination]

    hSBA-MenC/Y antibody cut-off values assessed were >=1:4 and >=1:8. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

17. hSBA-MenC and hSBA-MenY Antibody Titers [One month after the primary vaccination course]

    Titres are expressed as Geometric Mean Titers (GMTs). The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

18. hSBA-MenC and hSBA-MenY Antibody Titers [Prior to the fourth dose vaccination and one month after fourth dose vaccination]

    Titers are expressed as Geometric Mean Titers (GMTs) The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

19. Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values [One month after the primary vaccination course]

    Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 microgram per milliliter (µg/mL) and >=2.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

20. Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values [Prior to the fourth dose vaccination and one month after fourth dose vaccination]

    Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 µg/mL and >=2.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

21. Anti-PSC and Anti-PSY Antibodies Concentrations [One month after the primary vaccination course]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per milliliter (µg/mL). The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

22. Anti-PSC and Anti-PSY Antibody Concentrations [Prior to the fourth dose vaccination and one month after fourth dose vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL). The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.

23. Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Value [One month after the primary vaccination course]

    Anti-PRP antibody cut-off values assessed were >=0.15 µg/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

24. Anti-PRP Antibody Concentrations [One month after the primary vaccination course and prior to the fourth dose vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL). This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

25. Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titers Equal to or Above the Cut-off Values [One month after the primary vaccination course]

    hSBA-MenC and hSBA-MenY antibody cut-off values assessed were >=1:4 and >=1:8. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

26. Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values [Prior to the fourth dose vaccination and 42 days after fourth dose vaccination]

    Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 µg/mL and >=2.0 µg/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

27. Anti-PSC and Anti-PSY Antibody Concentrations [Prior to the fourth dose vaccination and 42 days after fourth dose vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL). This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

28. Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above 0.15 Microgram Per Milliliter (µg/mL) [Prior to the fourth dose vaccination and 42 days after fourth vaccination]

    This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

29. Anti-PRP Antibody Concentrations [Prior to the fourth vaccination and 42 days after fourth vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

30. Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Concentrations Equal to or Above 1:4 [Prior to the fourth dose vaccination and 42 days after fourth vaccination]

    This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

31. Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 200 Milli-international Units Per Millilitre (mIU/mL) [42 days after fourth vaccination]

    The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 150 mIU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

32. Anti-measles Antibody Concentrations [42 days after fourth vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in milli-international units per milliliter (mIU/mL). The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 150 mIU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

33. Number of Subjects With Anti-mumps Titer Equal to or Above the Cut-off Values [42 days after fourth vaccination]

    Anti-mumps antibody cut-off values assessed were >=28 estimated dose 50 (ED50) and >=51 ED50. The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-mumps antibody titers below 24 ED50. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

34. Anti-mumps Antibody Titers [42 days after fourth vaccination]

    Titers are expressed as Geometric Mean Titers (GMTs). The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody titers below 24 ED50. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

35. Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 4 International Units Per Millilitre (IU/mL) [42 days after fourth vaccination]

    The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-rubella antibody concentrations below 4 IU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

36. Anti-rubella Antibody Concentrations [42 days after fourth vaccination]

    Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in international units per milliliter (IU/mL). The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-rubella antibody concentrations below 4 IU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

37. Number of Subjects With Anti-varicella Titer Equal to or Above 1:40 [42 days after fourth vaccination]

    The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-rubella antibody concentrations below 1:5 This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

38. Anti-varicella Antibody Titers [42 days after fourth vaccination]

    Titers are expressed as Geometric Mean Titers (GMTs) The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-varicella antibody titers below 1:5 This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

39. Number of Subjects With Anti-H1N1, Anti-H3N2 and Anti-influenza-B (Anti B) Antibody Titers Equal to or Above 1:40 [Prior to the fourth dose vaccination and one month after the fourth dose vaccination]

    anti-H1N1, anti-H3N2 and anti-influenza-B (anti B) antibody were measured by hemagglutination inhibition assay (HIA), in subjects who received 2 doses of influenza vaccine within the same influenza season of which at least one dose is concomitant with the study vaccine. For the purposes of this study, concomitant administration of influenza vaccine was defined as administration within 28 days before to 7 days after administration of study vaccines. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based.

40. Number of Subjects Reporting Fever Above 39.5 Degrees Celsius/103.1 Degrees Fahrenheit [In the 4-day (Day 0-3) follow-up period after primary vaccination course]

    Fever is defined as temperature (rectal or axillary/tympanic) above 39.5 degrees Celsius (°C) or 103.1 degrees Fahrenheit (°F).

41. Number of Subjects Reporting Fever Above 39.5 Degrees Celsius/103.1 Degrees Fahrenheit [In the 4-day (Day0-3) follow-up period after the fourth dose]

    Fever is defined as temperature (rectal or axillary/tympanic) above 39.5 degrees Celsius (°C) or 103.1 degrees Fahrenheit (°F).

42. Number of Subjects Reporting Solicited Local and General Symptoms [Within the 4 days (Day 0-3) following each dose of the primary vaccination course]

    Solicited local symptoms assessed were pain, redness and swelling. Solicited genral symptoms assessed were fever, irritability/fussiness, drowsiness and loss of appetite. Fever is defined as temperature (rectal or axillary/tympanic) equal to or above 38.0°C.

43. Number of Subjects Reporting Solicited Local and General Symptoms [Within the 4 days (Day 0-3) post-vaccination period following the fourth dose]

    Solicited local symptoms assessed were pain, redness, swelling and an increase in limb circumference. Solicited general symptoms assessed were fever, irritability/fussiness, drowsiness and lost of appetite. Fever is defined as temperature (rectal or axillary/tympanic) equal to or above 38.0°C

44. Number of Subjects Reporting Unsolicited Adverse Events (AEs) [Within 31 days (Day 0-30) following the primary vaccination course]

    Unsolicited AE covers any AE 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.

45. Number of Subjects Reporting Unsolicited Adverse Events (AEs) [Within 31 days (Day 0-30) following the fourth dose]

    Unsolicited AE covers any AE 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.

46. Number of Subjects Reporting Increased Circumferential Swelling at the Injection Limb(s) [Within 4 days (Day 0 to Day 3) after fourth dose vaccination]

    Increased circumferential swelling defined as either swelling with a diameter of >50 mm or a >50 mm increase in the circumference of the mid-limb when compared to the baseline (pre-vaccination) measurement, or any diffuse swelling that interferes with or prevents everyday activities (for example, active playing, eating, sleeping).

47. Number of Subjects Reporting General Symptoms Specific to Measles, Mumps, Rubella and Varicella Vaccination [Within 43 days (Day 0 through Day 42) after vaccination]

    Symptoms assessed were fever, rash/exanthem, parotid/salivary gland swelling, and any suspected signs of meningism including febrile convulsions. Fever is defined as temperature (rectal or axillary/tympanic) equal to or above 38.0°C.

48. Number of Subjects Reporting Serious Adverse Events (SAEs) [From Dose 0 through 6 months after the last primary dose or untill administration of the fourth dose]

    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.

49. Number of Subjects Reporting Serious Adverse Events (SAEs) [From the fourth dose through the end of the 6-month safety follow-up]

    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.

50. Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCDs) [From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose]

    NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.

51. Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCDs) [From the fourth dose through the end of the 6-month safety follow-up]

    NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.

52. Number of Subjects Reporting Rash [From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose]

    Rash assessed was hives, idiopathic thrombocytopenic purpura, petechiae.

53. Number of Subjects Reporting Rash [From the fourth dose through the end of the 6-month safety follow-up]

    Rash assessed was hives, idiopathic thrombocytopenic purpura, petechiae.

54. Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits [From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose]

    Emergency room (ER) visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.

55. Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits. [From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose]

    Physicians (MD) office visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.

56. Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits [From the fourth dose through the end of the 6-month safety follow-up]

    Emergency room (ER) visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.

57. Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits [From the fourth dose through the end of the 6-month safety follow-up]

    Physicians (MD) office visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.

58. Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL). [Prior to the fourth dose vaccination]

    This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

59. Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titer Equal to or Above 1:8. [Prior to the fourth dose vaccination]

    This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 15 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

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

• A 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.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Born after 36 weeks gestation.

• 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.

• Infants may have received a birth dose of Bacillus Calmette-Guérin (BCG) vaccine.

Exclusion Criteria:

• 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 since birth.

• Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine(s). (Synagis® [palivizumab, MedImmune], Prevnar (Prevenar), rotavirus vaccine, and influenza vaccine are allowed.

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

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

• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required).

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, 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.

• Concurrent participation in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

Additional specific criteria for the US subjects in Cohort 1. In addition, for Cohorts 2 and 3, subjects should not be administered M-M-R II and Varivax if any of these criteria apply:

• History of measles, mumps, rubella or varicella.

• Previous vaccination against measles, mumps, rubella or varicella.

• Hypersensitivity to any component of the vaccines, including gelatin or neomycin.

• Patients receiving immunosuppressive therapy.

• Individuals with blood dyscrasias, leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic systems.

• Individuals with primary and acquired immunodeficiency states.

• Individuals with a family history of congenital or hereditary immunodeficiency, until the immune competence of the potential vaccine recipient is demonstrated.

• Individuals with active tuberculosis.

• Acute disease at time of booster vaccination.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35216
2	GSK Investigational Site	Birmingham	Alabama	United States	35235
3	GSK Investigational Site	Phoenix	Arizona	United States	85003
4	GSK Investigational Site	Bryant	Arkansas	United States	72011
5	GSK Investigational Site	Fayetteville	Arkansas	United States	72703
6	GSK Investigational Site	Little Rock	Arkansas	United States	72202
7	GSK Investigational Site	Little Rock	Arkansas	United States	72205
8	GSK Investigational Site	East Artesia	California	United States	90706
9	GSK Investigational Site	Fountain Valley	California	United States	92708
10	GSK Investigational Site	Fresno	California	United States	93710
11	GSK Investigational Site	Fresno	California	United States	93720
12	GSK Investigational Site	Fresno	California	United States	93726
13	GSK Investigational Site	La Jolla	California	United States	92037
14	GSK Investigational Site	Oakland	California	United States	94609
15	GSK Investigational Site	Paramount	California	United States	90723
16	GSK Investigational Site	Rolling Hills Estates	California	United States	90274
17	GSK Investigational Site	Sacramento	California	United States	95817
18	GSK Investigational Site	West Covina	California	United States	91790
19	GSK Investigational Site	Longmont	Colorado	United States	80501
20	GSK Investigational Site	Norwich	Connecticut	United States	06360
21	GSK Investigational Site	Cocoa Beach	Florida	United States	32931
22	GSK Investigational Site	Melbourne	Florida	United States	332901
23	GSK Investigational Site	Pembroke Pines	Florida	United States	33024
24	GSK Investigational Site	Rockledge	Florida	United States	32955
25	GSK Investigational Site	Nampa	Idaho	United States	208 463 3126
26	GSK Investigational Site	Des Moines	Iowa	United States	50266
27	GSK Investigational Site	Des Moines	Iowa	United States	50309
28	GSK Investigational Site	Arkansas City	Kansas	United States	67005
29	GSK Investigational Site	Kansas City	Kansas	United States	66160
30	GSK Investigational Site	Bardstown	Kentucky	United States	40004
31	GSK Investigational Site	Lexington	Kentucky	United States	40503
32	GSK Investigational Site	Louisville	Kentucky	United States	40272
33	GSK Investigational Site	Bossier City	Louisiana	United States	71111
34	GSK Investigational Site	Baltimore	Maryland	United States	21201
35	GSK Investigational Site	Boston	Massachusetts	United States	02118
36	GSK Investigational Site	Fall River	Massachusetts	United States	02724
37	GSK Investigational Site	Jamaica Plain	Massachusetts	United States	02130
38	GSK Investigational Site	Kalamazoo	Michigan	United States	49008
39	GSK Investigational Site	Portage	Michigan	United States	49024
40	GSK Investigational Site	Stevensville	Michigan	United States	49127
41	GSK Investigational Site	Brainerd	Minnesota	United States	56401
42	GSK Investigational Site	Saint Paul	Minnesota	United States	55108
43	GSK Investigational Site	Omaha	Nebraska	United States	68131
44	GSK Investigational Site	North Las Vegas	Nevada	United States	89025
45	GSK Investigational Site	Bronx	New York	United States	10467
46	GSK Investigational Site	Ithaca	New York	United States	14850
47	GSK Investigational Site	New Hartford	New York	United States	13413
48	GSK Investigational Site	Rochester	New York	United States	14618
49	GSK Investigational Site	Stony Brook	New York	United States	11794
50	GSK Investigational Site	Syracuse	New York	United States	13210
51	GSK Investigational Site	Durham	North Carolina	United States	27705
52	GSK Investigational Site	Durham	North Carolina	United States	27710
53	GSK Investigational Site	Raleigh	North Carolina	United States	27609
54	GSK Investigational Site	Sylva	North Carolina	United States	28779
55	GSK Investigational Site	Boardman	Ohio	United States	44512
56	GSK Investigational Site	Canton	Ohio	United States	44718
57	GSK Investigational Site	Cleveland	Ohio	United States	44121
58	GSK Investigational Site	Columbus	Ohio	United States	43205
59	GSK Investigational Site	Huber Heights	Ohio	United States	45424
60	GSK Investigational Site	South Euclid	Ohio	United States	44121
61	GSK Investigational Site	Tulsa	Oklahoma	United States	74127
62	GSK Investigational Site	Gresham	Oregon	United States	97030
63	GSK Investigational Site	Beaver Falls	Pennsylvania	United States	15010
64	GSK Investigational Site	Erie	Pennsylvania	United States	16501
65	GSK Investigational Site	Greenville	Pennsylvania	United States	16125
66	GSK Investigational Site	Hershey	Pennsylvania	United States	17033-0850
67	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19114
68	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15212
69	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213
70	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15236
71	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15241
72	GSK Investigational Site	Sellersville	Pennsylvania	United States	18960
73	GSK Investigational Site	Providence	Rhode Island	United States	02903
74	GSK Investigational Site	Charleston	South Carolina	United States	29406
75	GSK Investigational Site	Lexington	South Carolina	United States	29072
76	GSK Investigational Site	Amarillo	Texas	United States	79124
77	GSK Investigational Site	Fort Worth	Texas	United States	76107
78	GSK Investigational Site	Galveston	Texas	United States	77555-0188
79	GSK Investigational Site	San Antonio	Texas	United States	78205
80	GSK Investigational Site	Temple	Texas	United States	76508
81	GSK Investigational Site	Layton	Utah	United States	84041
82	GSK Investigational Site	Pleasant Grove	Utah	United States	84062
83	GSK Investigational Site	Saint George	Utah	United States	84790
84	GSK Investigational Site	South Jordan	Utah	United States	84095
85	GSK Investigational Site	Mechanicsville	Virginia	United States	23111
86	GSK Investigational Site	Norfolk	Virginia	United States	23510
87	GSK Investigational Site	Vancouver	Washington	United States	98664
88	GSK Investigational Site	La Crosse	Wisconsin	United States	54601
89	GSK Investigational Site	Randwick	New South Wales	Australia	2031
90	GSK Investigational Site	Herston	Queensland	Australia	4029
91	GSK Investigational Site	South Brisbane	Queensland	Australia	4101
92	GSK Investigational Site	Carlton	Victoria	Australia	3053
93	GSK Investigational Site	Mexico, D.F.		Mexico	06720

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Bryant K, McVernon J, Marchant C, Nolan T, Marshall G, Richmond P, Marshall H, Nissen M, Lambert S, Aris E, Mesaros N, Miller J. Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials. Hum Vaccin Immunother. 2012 Aug;8(8):1036-41. doi: 10.4161/hv.20357. Epub 2012 Aug 1.
• Bryant KA et al. Immune response to measles, mumps, rubella (MMR) and varicella (V) vaccine coadministered with a fourth dose of Haemophilus influenzae type b - Neisseria meningitidis serogroups C and Y - tetanus toxoid conjugate (HibMenCY) vaccine in toddlers. Abstract presented at the Annual meeting of Pediatric Academic Societies (PAS). Vancouver, Canada, 1-4 May 2010.
• Bryant KA, Marshall GS, Marchant CD, Pavia-Ruiz N, Nolan T, Rinderknecht S, Blatter M, Aris E, Lestrate P, Boutriau D, Friedland LR, Miller JM. Immunogenicity and safety of H influenzae type b-N meningitidis C/Y conjugate vaccine in infants. Pediatrics. 2011 Jun;127(6):e1375-85. doi: 10.1542/peds.2009-2992. Epub 2011 May 29.
• 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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00289783
• Other Study ID Numbers: 103813; 105067
• First Posted: Feb 10, 2006
• Last Update Posted: Aug 24, 2018
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Primary and booster vaccination; Neisseria meningitidis; Hib disease; Meningococcal vaccine; Meningococcal disease; Children; Immunogenicity; Safety; Infants
• Additional relevant MeSH terms: Influenza, Human; Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Recruitment Details	Subjects were randomized at the beginning of the primary phase and kept their group assignment during the fourth dose vaccination phase. The study protocol identified 3 different study cohorts : United States (US) Safety and Immunogenicity (Cohort 1), Safety Only (Cohort 2: from all investigation sites), Non-US Safety and Immunogenicity (Cohort 3).
Pre-assignment Detail	The data for 261 subjects from one study center in the US were not included in the analyses as vaccine accountability could not be fully reconciled (i.e. treatment group assignment for the different subjects could not be verified).

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Period Title: Primary Phase
STARTED	3136	1044
COMPLETED	2888	961
NOT COMPLETED	248	83
Period Title: Primary Phase
STARTED	2769	923
COMPLETED	2682	899
NOT COMPLETED	87	24

Baseline Characteristics

Arm/Group Title	Menhibrix Group	ActHIB Group	Total
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Total of all reporting groups
Overall Participants	3136	1044	4180
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	2.11 (0.26)	2.11 (0.27)	2.11 (0.27)
Sex: Female, Male (Count of Participants)
Female	1523 48.6%	498 47.7%	2021 48.3%
Male	1613 51.4%	546 52.3%	2159 51.7%

Outcome Measures

1. Primary Outcome

Title	Anti-Polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	162	180	176	518	171
Geometric Mean (95% Confidence Interval) [microgram per milliliter (µg/mL)]	10.170	11.424	11.438	11.021	6.463

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for polyribosylribitol phosphate (PRP) as measured by ELISA.
	Type of Statistical Test	Equivalence
	Comments	Criteria for lot-to-lot consistency (1 month after primary vaccination): For each pair of lots and for the immune response to anti-PRP measured by Enzyme Linked Immunosorbent Assay (ELISA) the two-sided 95% confidence interval (CI) on the geometric mean concentrations (GMCs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix C Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for polyribosylribitol phosphate (PRP) as measured by ELISA.
	Type of Statistical Test	Equivalence
	Comments	Criteria for lot-to-lot consistency (1 month after primary vaccination): For each pair of lots and for the immune response to anti-PRP measured by ELISA the two-sided 95% confidence interval (CI) on the geometric mean concentrations (GMCs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Menhibrix B Group, Menhibrix C Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for polyribosylribitol phosphate (PRP) as measured by ELISA.
	Type of Statistical Test	Equivalence
	Comments	Criteria for lot-to-lot consistency (1 month after primary vaccination): For each pair of lots and for the immune response to anti-PRP measured by ELISA the two-sided 95% confidence interval (CI) on the geometric mean concentrations (GMCs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1
	Confidence Interval	(2-Sided) 95%; 0.8 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Neisseria Meningitidis Serogroup C (MenC) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers
Description	Titers were expressed as Geometric Mean Titers (GMTs) This analysis occured on the cohort 1 : Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	158	168	165	491	164
Geometric Mean (95% Confidence Interval) [Titers]	910.0	1118.0	885.7	967.6	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for N. meningitidis serogroup C (MenC) as measured by a serum bactericidal assay using human complement (hSBA).
	Type of Statistical Test	Equivalence
	Comments	For each pair of lots and for the immune response to hSBA-MenC, the two-sided 95% confidence interval (CI) on the geometric mean titers (GMTs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix C Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for N. meningitidis serogroup C (MenC) as measured by a serum bactericidal assay using human complement (hSBA).
	Type of Statistical Test	Equivalence
	Comments	For each pair of lots and for the immune response to hSBA-MenC, the two-sided 95% confidence interval (CI) on the geometric mean titers (GMTs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Menhibrix B Group, Menhibrix C Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for N. meningitidis serogroup C (MenC) as measured by a serum bactericidal assay using human complement (hSBA).
	Type of Statistical Test	Equivalence
	Comments	For each pair of lots and for the immune response to hSBA-MenC, the two-sided 95% confidence interval (CI) on the geometric mean titers (GMTs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.6 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Neisseria Meningitidis Serogroup Y (MenY) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers
Description	Titers are expressen as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	150	168	163	481	162
Geometric Mean (95% Confidence Interval) [Titers]	178.9	288.1	249.6	236.6	2.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for N. meningitidis serogroup Y (MenY) as measured by a serum bactericidal assay using human complement (hSBA).
	Type of Statistical Test	Equivalence
	Comments	For each pair of lots and for the immune response to hSBA-MenY, the two-sided 95% confidence interval (CI) on the geometric mean titers (GMTs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 1.14 to 2.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix C Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for N. meningitidis serogroup Y (MenY) as measured by a serum bactericidal assay using human complement (hSBA).
	Type of Statistical Test	Equivalence
	Comments	For each pair of lots and for the immune response to hSBA-MenY, the two-sided 95% confidence interval (CI) on the geometric mean titers (GMTs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; 0.99 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Menhibrix B Group, Menhibrix C Group
	Comments	To demonstrate the lot-to-lot consistency of 3 manufacturing lots of Hib-MenCY-TT vaccine co-administered with DTPa-HBV-IPV vaccine following 3 primary doses in terms of immunogenicity for N. meningitidis serogroup Y (MenY) as measured by a serum bactericidal assay using human complement (hSBA).
	Type of Statistical Test	Equivalence
	Comments	For each pair of lots and for the immune response to hSBA-MenY, the two-sided 95% confidence interval (CI) on the geometric mean titers (GMTs) ratio between lots is within the [0.5; 2.0] interval.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	hSBA-MenC Antibody Titers
Description	Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and 42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	331	119
hSBA-MenC [post-dose 4]	2039.8	4.3
hSBA-MenC [pre-dose 4]	180.3	3.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group
	Comments	To evaluate the specific effect of a fourth dose of Menhibrix vaccine co-administered with M-M-R II and Varivax vaccines at 12 to 15 months of age in terms of a fourth dose vaccine response as measured by hSBA-MenC.
	Type of Statistical Test	Non-Inferiority
	Comments	Criteria for immunogenicity of MenC (42 days after the fourth dose): Lower limit of the asymptotic 95% CI for the geometric mean of individual ratio of post-dose 4/pre-dose 4 is ≥ 2.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	12
	Confidence Interval	(2-Sided) 95%; 10.4 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Menhibrix B Group
	Comments	To evaluate the specific effect of a fourth dose of Menhibrix vaccine co-administered with M-M-R II and Varivax vaccines at 12 to 15 months of age in terms of a fourth dose vaccine response as measured by hSBA-MenC.
	Type of Statistical Test	Non-Inferiority
	Comments	Point estimate = Lower limit (LL) = Upper limit (UL) as LL and UL values were not available due to the departure from lognormal distribution (large number of imputed values)
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; 1.4 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	hSBA-MenY Antibody Titers
Description	Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and 42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	342	120
hSBA-MenY [post-dose 4]	1389.5	48.6
hSBA-MenY [pre-dose 4]	119.1	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group
	Comments	To evaluate the specific effect of a fourth dose of Menhibrix vaccine co-administered with M-M-R II and Varivax vaccines at 12 to 15 months of age in terms of a fourth dose vaccine response as measured by hSBA-MenY.
	Type of Statistical Test	Non-Inferiority
	Comments	Criteria for immunogenicity of MenY (42 days after the fourth dose): Lower limit of the asymptotic 95% CI for the geometric mean of individual ratio of post-dose 4/pre-dose 4 is ≥ 2.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	11.8
	Confidence Interval	(2-Sided) 95%; 10.2 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Menhibrix B Group
	Comments	To evaluate the specific effect of a fourth dose of Menhibrix vaccine co-administered with M-M-R II and Varivax vaccines at 12 to 15 months of age in terms of a fourth dose vaccine response as measured by hSBA-MenY.
	Type of Statistical Test	Non-Inferiority
	Comments	Point estimate = Lower limit (LL) = Upper limit (UL) as LL and UL values were not available due to the departure from lognormal distribution (large number of imputed values).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT ratio
	Estimated Value	21.1
	Confidence Interval	(2-Sided) 95%; 21.1 to 21.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL)
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	162	180	176	518	171
Count of Participants [Participants]	158 5%	175 16.8%	166 4%	499 NaN	156 NaN

7. Primary Outcome

Title	Number of Subjects With hSBA-MenC Titer Equal to or Above 1:8
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	331	119
Count of Participants [Participants]	326 10.4%	26 2.5%

8. Primary Outcome

Title	Number of Subjects With hSBA-MenY Titer Equal to or Above 1:8
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	342	120
Count of Participants [Participants]	338 10.8%	87 8.3%

9. Primary Outcome

Title	Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 150 Milli-international Units Per Milli-liter (mIU/ML)
Description	The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 150 mIU/mL. Co-administration with MMR-II vaccine
Time Frame	42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	852	286
Count of Participants [Participants]	815 26%	274 26.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate the non-inferiority of M-M-R II vaccine when co-administered with a fourth dose of Menhibrix vaccine compared to M-M-R II vaccine co-administered with a fourth dose of PedvaxHIB vaccine, each co-administered with Varivax vaccine.
	Type of Statistical Test	Non-Inferiority
	Comments	Lower limit of the standardized asymptotic 95% CI for the difference (Menhibrix vaccine fourth dose group minus ActHIB fourth dose group) in the percentage of subjects with seroconversion ≥ 150 mIU/mL, in initially seronegative subjects (<150 mIU/mL), for anti-measles antibody is ≥-5% (clinical limit for non-inferiority).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -2.56 to 3.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Primary Outcome

Title	Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	361	126
Count of Participants [Participants]	358 11.4%	125 12%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate that, following a fourth dose, the immune response to Hib polysaccharide (PRP) in the group that received 3 primary vaccine doses of Menhibrix vaccine and a fourth dose of Menhibrix vaccine coadministered with M-M-R II and Varivax vaccines was non-inferior to the corresponding immune response in the group that received 3 primary vaccine doses of ActHIB vaccine and a fourth dose of PedvaxHIB vaccine co-administered with M-M-R II and Varivax vaccines.
	Type of Statistical Test	Non-Inferiority
	Comments	Criteria for non-inferiority (42 days after the fourth dose): Lower limit of the two-sided standardized asymptotic 95% CI on the difference (Menhibrix vaccine fourth dose group minus ActHIB fourth dose group) in the percentage of subjects with anti-PRP concentration ≥ 1.0 µg/mL is ≥ -10% (clinical limit for non-inferiority)
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -1.78 to 3.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Primary Outcome

Title	Number of Subjects With Anti-mumps Titer Equal to or Above 28 Estimated Dose 50 (ED50)
Description	The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-mumps antibody titers below 28 ED50 Co-administration with MMR-II vaccine.
Time Frame	42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	601	191
Count of Participants [Participants]	595 19%	191 18.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate the non-inferiority of M-M-R II vaccine when co-administered with a fourth dose of Menhibrix vaccine compared to M--M-R II vaccine co-administered with a fourth dose of PedvaxHIB vaccine, each co-administered with Varivax vaccine.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for non-inferiority (42 days after fourth dose vaccination): Lower limit of the standardized asymptotic 95% CI for the difference (Menhibrix vaccine fourth dose group minus ActHIB fourth dose group) in the percentage of subjects with a seroconversion ≥28 ED50, in subjects with initial anti-mumps antibody < 28 ED50, for anti-mumps antibody is ≥ -5% (clinical limit for non-inferiority).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-1
	Confidence Interval	(2-Sided) 95%; -2.16 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Primary Outcome

Title	Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 10 International Units Per Milli-litre (IU/mL)
Description	The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 4 IU/mL. Co-administration with MMR-II vaccine.
Time Frame	42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	850	285
Count of Participants [Participants]	848 27%	284 27.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate the non-inferiority of M-M-R II vaccine when co-administered with a fourth dose of Menhibrix vaccine compared to M-M-R II vaccine co-administered with a fourth dose of PedvaxHIB vaccine, each co-administered with Varivax vaccine.
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for non-inferiority (42 days after fourth dose vaccination): Lower limit of the standardized asymptotic 95% CI for the difference (Menhibrix vaccine fourth dose group minus ActHIB fourth dose group) in the percentage of subjects with seroresponse ≥10 IU/ml, in initially seronegative subjects (< 4 IU/ml), for anti-rubella antibody is ≥ -5% (clinical limit for non-inferiority).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.57 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Primary Outcome

Title	Number of Subjects With Anti-varicella Titer Equal to or Above 1:5
Description	The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody titer below 1:5. Co-administration with Varivax vaccine.
Time Frame	42 days after the fourth dose

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	723	223
Count of Participants [Participants]	722 23%	223 21.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Menhibrix A Group, Menhibrix B Group
	Comments	To demonstrate the non-inferiority of Varivax vaccine co-administered with a fourth dose of Menhibrix vaccine compared to Varivax vaccine co-administered with a fourth dose of PedvaxHIB vaccine, each co-administered with M-M-R II vaccine in terms of immunogenicity to varicella as measured by fluorescent antibody to membrane antigen (FAMA).
	Type of Statistical Test	Non-Inferiority
	Comments	Criterion for non-inferiority (42 days after the fourth dose vaccination): Lower limit of the standardized asymptotic 95% CI for the difference (Menhibrix vaccine fourth dose group minus ActHIB fourth dose group) in the percentage of subjects with seroconversion ≥ 1:5 dilution, in initially seronegative subjects (< 1:5), for anti-varicella antibody is ≥ -10% (clinical limit for non-inferiority).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.78 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Number of Subjects With Anti-tetanus (Anti-T) and Anti-diphtheria Toxoid (Anti-D) Antibody Concentrations Equal to or Above 0.1 International Units Per Millilitre (IU/mL)
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	365	120
Anti-D	365 11.6%	120 11.5%
Anti-T	365 11.6%	120 11.5%

15. Secondary Outcome

Title	Anti-D and Anti-T Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in international units per milliliter (IU/mL). This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	365	120
Anti-D	2.0	2.2
Anti-T	3.9	1.9

16. Secondary Outcome

Title	Number of Subjects With Anti Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above 10.0 Milli-international Units Per Millilitre (mIU/mL)
Description	Results are stratified by the presence or absence of a birth dose of hepatitis B vaccine. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	194	47
Anti-HBs with Hepatitis B at birth	193 6.2%	47 4.5%
Anti-HBs without Hepatitis B at birth	17 0.5%	8 0.8%

17. Secondary Outcome

Title	Anti-HBS Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in milli-International units per milliliter (mIU/mL) Results are stratified by the presence or absence of a birth dose of hepatitis B vaccine. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	194	47
Anti-HBs with Hepatitis B at birth	1963.2	2187.6
Anti-HBs without Hepatitis B at birth	1672.7	3593.2

18. Secondary Outcome

Title	Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations Equal to or Above 5 ELISA Units Per Millilitre (EL.U/mL)
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	327	101
Anti-PT	327 10.4%	100 9.6%
Anti-FHA	324 10.3%	97 9.3%
Anti-PRN	321 10.2%	99 9.5%

19. Secondary Outcome

Title	Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	327	101
Anti-PT	57.7	65.6
Anti-FHA	243.8	293.6
Anti-PRN	98.6	103.1

20. Secondary Outcome

Title	Number of Subjects With Anti-poliovirus Types 1, 2 and 3 Equal to or Above 8 Estimated Dose 50 (ED50)
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	285	90
Anti-Polio 1	285 9.1%	90 8.6%
Anti-Polio 2	285 9.1%	90 8.6%
Anti-Polio 3	285 9.1%	89 8.5%

21. Secondary Outcome

Title	Anti-poliovirus Types 1, 2 and 3 Titers
Description	Titers are expressed as Geometric Mean Titers (GMTs) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	285	90
Anti-Polio 1	591.8	590.7
Anti-Polio 2	496.7	452.7
Anti-Polio 3	1367.7	1239.2

22. Secondary Outcome

Title	Number of Subjects With Antibodies to Neisseria Meningitidis Serogroup C and Y Polysaccharide Capsule (Anti-PSC and Anti-PSY) Concentrations Equal to or Above the Cut-off Values
Description	Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 microgram per milliliter (µg/mL) and >=2.0 µg/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	421	119
Anti-PSC >=0.3 µg/mL	418 13.3%	5 0.5%
Anti-PSY >=0.3 µg/mL	402 12.8%	1 0.1%
Anti-PSC >=2.0 µg/mL	379 12.1%	2 0.2%
Anti-PSY >=2.0 µg/mL	396 12.6%	0 0%

23. Secondary Outcome

Title	Anti-PSC and Anti-PSY Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per milliliter (µg/mL) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after primary vaccination

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	421	119
Anti-PSC	5.8	0.2
Anti-PSY	17.5	0.2

24. Secondary Outcome

Title	Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Values
Description	Anti-PRP antibody cut-off values assessed were >=0.15 microgram per milliliter (µg/mL) and >=1.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	49	42	43	134	46
Anti-PRP >=0.15 µg/mL	49 1.6%	42 4%	43 1%	134 NaN	46 NaN
Anti-PRP >=1.0 µg/mL	49 1.6%	42 4%	43 1%	134 NaN	46 NaN

25. Secondary Outcome

Title	Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Values
Description	Anti-PRP antibody cut-off values assessed were >=0.15 microgram per milliliter (µg/mL) and >=1.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and one month after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	40	13
Anti-PRP pre-dose 4 >=0.15 µg/mL	38 1.2%	12 1.1%
Anti-PRP pre-dose 4 >=1.0 µg/mL	33 1.1%	11 1.1%
Anti-PRP post-dose 4 >=0.15 µg/mL	40 1.3%	13 1.2%
Anti-PRP post-dose 4 >=1.0 µg/mL	40 1.3%	13 1.2%

26. Secondary Outcome

Title	Anti-PRP Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	49	42	43	134	46
Geometric Mean (95% Confidence Interval) [µg/mL]	24.984	24.050	20.489	23.165	29.759

27. Secondary Outcome

Title	Anti-PRP Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and one month after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	40	13
Anti-PRP Pre-dose 4	3.340	4.123
Anti-PRP Post-dose 4	132.965	92.800

28. Secondary Outcome

Title	Number of Subjects With hSBA-MenC and hSBA-MenY Titers Equal to or Above the Cut-off Values
Description	hSBA-MenC/Y antibody cut-off values assessed were >=1:4 and >=1:8 The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	49	42	44	135	46
hSBA-MenC >=1:4	47 1.5%	42 4%	44 1.1%	133 NaN	2 NaN
hSBA-MenC >=1:8	47 1.5%	42 4%	44 1.1%	133 NaN	2 NaN
hSBA-MenY >=1:4	48 1.5%	42 4%	44 1.1%	134 NaN	1 NaN
hSBA-MenY >=1:8	48 1.5%	42 4%	44 1.1%	134 NaN	1 NaN

29. Secondary Outcome

Title	Number of Subjects With hSBA-MenC and hSBA-MenY Titers Equal to or Above the Cut-off Values
Description	hSBA-MenC/Y antibody cut-off values assessed were >=1:4 and >=1:8. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and one month after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	40	13
hSBA-MenC pre-dose 4 >=1:4	39 1.2%	2 0.2%
hSBA-MenC pre-dose 4 >=1:8	39 1.2%	2 0.2%
hSBA-MenC post-dose 4 >=1:4	39 1.2%	1 0.1%
hSBA-MenC post-dose 4 >=1:8	39 1.2%	1 0.1%
hSBA-MenY pre-dose 4 >=1:4	39 1.2%	3 0.3%
hSBA-MenY pre-dose 4 >=1:8	39 1.2%	3 0.3%
hSBA-MenY post-dose 4 >=1:4	40 1.3%	7 0.7%
hSBA-MenY post-dose 4 >=1:8	40 1.3%	7 0.7%

30. Secondary Outcome

Title	hSBA-MenC and hSBA-MenY Antibody Titers
Description	Titres are expressed as Geometric Mean Titers (GMTs). The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	49	42	44	135	46
hSBA-MenC	3055.8	3370.7	3119.3	3172.6	2.4
hSBA-MenY	666.5	916.7	989.6	837.2	2.2

31. Secondary Outcome

Title	hSBA-MenC and hSBA-MenY Antibody Titers
Description	Titers are expressed as Geometric Mean Titers (GMTs) The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and one month after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	40	13
hSBA-MenC pre-dose 4	504.7	3.6
hSBA-MenC post-dose 4	10132.9	2.5
hSBA-MenY pre-dose 4	446.5	5.3
hSBA-MenY post-dose 4	5775.8	27.4

32. Secondary Outcome

Title	Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values
Description	Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 microgram per milliliter (µg/mL) and >=2.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	134	46
Anti-PSC >=0.3 µg/mL	134 4.3%	2 0.2%
Anti-PSC >=2.0 µg/mL	134 4.3%	1 0.1%
Anti-PSY >=0.3 µg/mL	130 4.1%	1 0.1%
Anti-PSY >=2.0 µg/mL	130 4.1%	1 0.1%

33. Secondary Outcome

Title	Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values
Description	Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 µg/mL and >=2.0 µg/mL. The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and one month after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	40	13
Anti-PSC pre-dose 4 >=0.3 µg/mL	40 1.3%	0 0%
Anti-PSC pre-dose 4 >=2.0 µg/mL	22 0.7%	0 0%
Anti-PSC post-dose 4 >=0.3 µg/mL	39 1.2%	0 0%
Anti-PSC post-dose 4 >=2.0 µg/mL	39 1.2%	0 0%
Anti-PSY pre-dose 4 >=0.3 µg/mL	40 1.3%	0 0%
Anti-PSY pre-dose 4 >=2.0 µg/mL	36 1.1%	0 0%
Anti-PSY post-dose 4 >=0.3 µg/mL	40 1.3%	0 0%
Anti-PSY post-dose 4 >=2.0 µg/mL	40 1.3%	0 0%

34. Secondary Outcome

Title	Anti-PSC and Anti-PSY Antibodies Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per milliliter (µg/mL). The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary According-To-Protocol (ATP) cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol and met no elimination criteria during the study) for whom results were available for antibodies against the vaccine antigens after the third vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	134	46
Anti-PSC	13.4	0.2
Anti-PSY	36.7	0.2

35. Secondary Outcome

Title	Anti-PSC and Anti-PSY Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL). The analysis was performed on the cohort 3 (Non-US Safety and Immunogenicity): Cohort 3 was to include the subjects enrolled at 1 center in Mexico. Only descriptive immunogenicity results were reported for this cohort. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and one month after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	40	13
Anti-PSC pre-dose 4	2.20	0.15
Anti-PSC post-dose 4	15.63	0.15
Anti-PSY pre-dose 4	5.70	0.15
Anti-PSY post-dose 4	64.66	0.15

36. Secondary Outcome

Title	Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Value
Description	Anti-PRP antibody cut-off values assessed were >=0.15 µg/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary ATP cohort for immunogenicity included evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures and met no elimination criteria) for whom assay results were available for antibodies against at least 1 study vaccine antigen for the blood sample taken during primary vaccination (after the 3rd vaccine dose.

Arm/Group Title	Menhibrix Group	ActHIB Group	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	518	171	162	180	176
Count of Participants [Participants]	518 16.5%	168 16.1%	162 3.9%	180 NaN	176 NaN

37. Secondary Outcome

Title	Anti-PRP Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL). This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course and prior to the fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for safety included eligible subjects, who met inclusion criteria, who received 3 vaccine doses in the primary vaccination course, who received the fourth vaccine dose, who did not receive a vaccine not specified or forbidden and who were not excluded from from the Primary ATP cohort for immunogenicity.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	469	160
Anti-PRP post-primary	10.802	6.086
Anti-PRP pre-dose 4	1.615	0.832

38. Secondary Outcome

Title	Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titers Equal to or Above the Cut-off Values
Description	hSBA-MenC and hSBA-MenY antibody cut-off values assessed were >=1:4 and >=1:8. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	One month after the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary ATP cohort for immunogenicity included evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures and met no elimination criteria ) for whom assay results were available for antibodies against at least 1 study vaccine antigen for the blood sample taken during primary vaccination (after the 3rd vaccine dose

Arm/Group Title	Menhibrix Group	ActHIB Group	Menhibrix A Group	Menhibrix B Group	Menhibrix C Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot A co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot B co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of Menhibrix vaccine Lot C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	491	164	158	168	165
hSBA-MenC >=1:4	485 15.5%	11 1.1%	156 3.7%	167 NaN	162 NaN
hSBA-MenC >=1:8	485 15.5%	11 1.1%	156 3.7%	167 NaN	162 NaN
hSBA-MenY >=1:4	463 14.8%	3 0.3%	141 3.4%	165 NaN	157 NaN
hSBA-MenY >=1:8	461 14.7%	3 0.3%	140 3.3%	165 NaN	156 NaN

39. Secondary Outcome

Title	Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values
Description	Anti-PSC and anti-PSY antibody cut-off values assessed were >=0.3 µg/mL and >=2.0 µg/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and 42 days after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	334	109
Anti-PSC pre-dose 4 >=0.3 µg/mL	300 9.6%	3 0.3%
Anti-PSC pre-dose 4 >=2.0 µg/mL	73 2.3%	0 0%
Anti-PSC post-dose 4 >=0.3 µg/mL	313 10%	9 0.9%
Anti-PSC post-dose 4 >=2.0 µg/mL	262 8.4%	6 0.6%
Anti-PSY pre-dose 4 >=0.3 µg/mL	320 10.2%	1 0.1%
Anti-PSY pre-dose 4 >=2.0 µg/mL	235 7.5%	0 0%
Anti-PSY post-dose 4 >=0.3 µg/mL	332 10.6%	6 0.6%
Anti-PSY post-dose 4 >=2.0 µg/mL	325 10.4%	4 0.4%

40. Secondary Outcome

Title	Anti-PSC and Anti-PSY Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL). This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and 42 days after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	334	109
Anti-PSC pre-dose 4	1.04	0.16
Anti-PSC post-dose 4	4.81	0.19
Anti-PSY pre-dose 4	3.15	0.15
Anti-PSY post-dose 4	18.26	0.18

41. Secondary Outcome

Title	Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above 0.15 Microgram Per Milliliter (µg/mL)
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and 42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	361	126
Anti-PRP [post-dose 4]	361 11.5%	126 12.1%
Anti-PRP [pre-dose 4]	329 10.5%	98 9.4%

42. Secondary Outcome

Title	Anti-PRP Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in microgram per millilitre (µg/mL) This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth vaccination and 42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	361	126
Anti-PRP [post-dose 4]	34.851	20.200
Anti-PRP [pre-dose 4]	1.617	0.759

43. Secondary Outcome

Title	Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Concentrations Equal to or Above 1:4
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination and 42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	342	120
hSBA-MenC [post-dose 4]	326 10.4%	26 2.5%
hSBA-MenY [post-dose 4]	338 10.8%	87 8.3%
hSBA-MenC [pre-dose 4]	318 10.1%	12 1.1%
hSBA-MenY [pre-dose 4]	309 9.9%	6 0.6%

44. Secondary Outcome

Title	Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 200 Milli-international Units Per Millilitre (mIU/mL)
Description	The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 150 mIU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	852	286
Count of Participants [Participants]	812 25.9%	273 26.1%

45. Secondary Outcome

Title	Anti-measles Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in milli-international units per milliliter (mIU/mL). The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody concentrations below 150 mIU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	852	286
Geometric Mean (95% Confidence Interval) [mIU/mL]	1990.0	1989.5

46. Secondary Outcome

Title	Number of Subjects With Anti-mumps Titer Equal to or Above the Cut-off Values
Description	Anti-mumps antibody cut-off values assessed were >=28 estimated dose 50 (ED50) and >=51 ED50. The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-mumps antibody titers below 24 ED50. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	536	176
Anti-mumps >=28 ED50	532 17%	176 16.9%
Anti-mumps >=51 ED50	490 15.6%	160 15.3%

47. Secondary Outcome

Title	Anti-mumps Antibody Titers
Description	Titers are expressed as Geometric Mean Titers (GMTs). The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-measles antibody titers below 24 ED50. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	536	176
Geometric Mean (95% Confidence Interval) [Titers]	123.9	114.3

48. Secondary Outcome

Title	Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 4 International Units Per Millilitre (IU/mL)
Description	The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-rubella antibody concentrations below 4 IU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	850	285
Count of Participants [Participants]	850 27.1%	285 27.3%

49. Secondary Outcome

Title	Anti-rubella Antibody Concentrations
Description	Concentrations are given as Geometric Mean Concentrations (GMCs) and are expressed in international units per milliliter (IU/mL). The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-rubella antibody concentrations below 4 IU/mL. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	850	285
Geometric Mean (95% Confidence Interval) [IU/mL]	81.4	74.9

50. Secondary Outcome

Title	Number of Subjects With Anti-varicella Titer Equal to or Above 1:40
Description	The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-rubella antibody concentrations below 1:5 This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	723	223
Count of Participants [Participants]	722 23%	223 21.4%

51. Secondary Outcome

Title	Anti-varicella Antibody Titers
Description	Titers are expressed as Geometric Mean Titers (GMTs) The analysis was performed on initially seronegative subjects. Seronegative subjects are subjects with anti-varicella antibody titers below 1:5 This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	42 days after fourth vaccination

Outcome Measure Data

Analysis Population Description

The Pooled cohort consisted of all evaluable subjects in the Fourth dose ATP cohort for immunogenicity, HibMenCY-TT-008 and Cohort 1 from HibMenCY-TT-010

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	723	223
Geometric Mean (95% Confidence Interval) [Titers]	407.1	394.1

52. Secondary Outcome

Title	Number of Subjects With Anti-H1N1, Anti-H3N2 and Anti-influenza-B (Anti B) Antibody Titers Equal to or Above 1:40
Description	anti-H1N1, anti-H3N2 and anti-influenza-B (anti B) antibody were measured by hemagglutination inhibition assay (HIA), in subjects who received 2 doses of influenza vaccine within the same influenza season of which at least one dose is concomitant with the study vaccine. For the purposes of this study, concomitant administration of influenza vaccine was defined as administration within 28 days before to 7 days after administration of study vaccines. This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based.
Time Frame	Prior to the fourth dose vaccination and one month after the fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	5	4
Anti-H1N1 pre-dose 4	0 0%	0 0%
Anti-H1N1 post-dose 4	2 0.1%	1 0.1%
Anti-H3N2 pre-dose 4	0 0%	0 0%
Anti-H3N2 post-dose 4	3 0.1%	1 0.1%
Anti-B pre-dose 4	0 0%	0 0%
Anti-B post-dose 4	1 0%	1 0.1%

53. Secondary Outcome

Title	Number of Subjects Reporting Fever Above 39.5 Degrees Celsius/103.1 Degrees Fahrenheit
Description	Fever is defined as temperature (rectal or axillary/tympanic) above 39.5 degrees Celsius (°C) or 103.1 degrees Fahrenheit (°F).
Time Frame	In the 4-day (Day 0-3) follow-up period after primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3089	1015
Count of Participants [Participants]	46 1.5%	16 1.5%

54. Secondary Outcome

Title	Number of Subjects Reporting Fever Above 39.5 Degrees Celsius/103.1 Degrees Fahrenheit
Description	Fever is defined as temperature (rectal or axillary/tympanic) above 39.5 degrees Celsius (°C) or 103.1 degrees Fahrenheit (°F).
Time Frame	In the 4-day (Day0-3) follow-up period after the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2527	831
Count of Participants [Participants]	18 0.6%	5 0.5%

55. Secondary Outcome

Title	Number of Subjects Reporting Solicited Local and General Symptoms
Description	Solicited local symptoms assessed were pain, redness and swelling. Solicited genral symptoms assessed were fever, irritability/fussiness, drowsiness and loss of appetite. Fever is defined as temperature (rectal or axillary/tympanic) equal to or above 38.0°C.
Time Frame	Within the 4 days (Day 0-3) following each dose of the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3089	1016
Any Pain, Dose 1	1849 59%	672 64.4%
Any Pain, Dose 2	1679 53.5%	596 57.1%
Any Pain, Dose 3	1454 46.4%	522 50%
Any Pain, Across doses	2419 77.1%	819 78.4%
Any Redness, Dose 1	1152 36.7%	401 38.4%
Any Redness, Dose 2	1455 46.4%	483 46.3%
Any Redness, Dose 3	1409 44.9%	495 47.4%
Any Redness, Across doses	2052 65.4%	691 66.2%
Any Swelling, Dose 1	893 28.5%	281 26.9%
Any Swelling, Dose 2	1091 34.8%	350 33.5%
Any Swelling, Dose 3	1110 35.4%	381 36.5%
Any Swelling, Across doses	1707 54.4%	568 54.4%
Any Drowsiness, Dose 1	1864 59.4%	655 62.7%
Any Drowsiness, Dose 2	1588 50.6%	552 52.9%
Any Drowsiness, Dose 3	1260 40.2%	444 42.5%
Any Drowsiness, Across doses	2418 77.1%	804 77%
Any Temperature, Dose 1	688 21.9%	228 21.8%
Any Temperature, Dose 2	803 25.6%	276 26.4%
Any Temperature, Dose 3	609 19.4%	206 19.7%
Any Temperature, Across doses	1434 45.7%	463 44.3%
Any Irritability, Dose 1	2156 68.8%	782 74.9%
Any Irritability, Dose 2	2074 66.1%	708 67.8%
Any Irritability, Dose 3	1771 56.5%	600 57.5%
Any Irritability, Across doses	2740 87.4%	926 88.7%
Any Loss of appetite, Dose 1	1024 32.7%	375 35.9%
Any Loss of appetite, Dose 2	921 29.4%	317 30.4%
Any Loss of appetite, Dose 3	828 26.4%	285 27.3%
Any Loss of appetite, Across doses	1764 56.3%	609 58.3%

56. Secondary Outcome

Title	Number of Subjects Reporting Solicited Local and General Symptoms
Description	Solicited local symptoms assessed were pain, redness, swelling and an increase in limb circumference. Solicited general symptoms assessed were fever, irritability/fussiness, drowsiness and lost of appetite. Fever is defined as temperature (rectal or axillary/tympanic) equal to or above 38.0°C
Time Frame	Within the 4 days (Day 0-3) post-vaccination period following the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Pain	1319 42.1%	494 47.3%
Redness	1213 38.7%	463 44.3%
Swelling	936 29.8%	334 32%
Increase in limb circumference	1489 47.5%	503 48.2%
Drowsiness	1088 34.7%	381 36.5%
Fever	341 10.9%	134 12.8%
Irritability	1482 47.3%	534 51.1%
Loss of appetite	825 26.3%	287 27.5%

57. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Description	Unsolicited AE covers any AE 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.
Time Frame	Within 31 days (Day 0-30) following the primary vaccination course

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3136	1044
Count of Participants [Participants]	1820 58%	602 57.7%

58. Secondary Outcome

Title	Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Description	Unsolicited AE covers any AE 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.
Time Frame	Within 31 days (Day 0-30) following the fourth dose

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Count of Participants [Participants]	1010 32.2%	334 32%

59. Secondary Outcome

Title	Number of Subjects Reporting Increased Circumferential Swelling at the Injection Limb(s)
Description	Increased circumferential swelling defined as either swelling with a diameter of >50 mm or a >50 mm increase in the circumference of the mid-limb when compared to the baseline (pre-vaccination) measurement, or any diffuse swelling that interferes with or prevents everyday activities (for example, active playing, eating, sleeping).
Time Frame	Within 4 days (Day 0 to Day 3) after fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Count of Participants [Participants]	1489 47.5%	503 48.2%

60. Secondary Outcome

Title	Number of Subjects Reporting General Symptoms Specific to Measles, Mumps, Rubella and Varicella Vaccination
Description	Symptoms assessed were fever, rash/exanthem, parotid/salivary gland swelling, and any suspected signs of meningism including febrile convulsions. Fever is defined as temperature (rectal or axillary/tympanic) equal to or above 38.0°C.
Time Frame	Within 43 days (Day 0 through Day 42) after vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	545	175
Meningismus	0 0%	0 0%
Parotiditis	0 0%	0 0%
Rash	59 1.9%	19 1.8%
Fever	211 6.7%	70 6.7%

61. Secondary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs)
Description	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.
Time Frame	From Dose 0 through 6 months after the last primary dose or untill administration of the fourth dose

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3136	1044
Count of Participants [Participants]	126 4%	50 4.8%

62. Secondary Outcome

Title	Number of Subjects Reporting Serious Adverse Events (SAEs)
Description	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.
Time Frame	From the fourth dose through the end of the 6-month safety follow-up

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Count of Participants [Participants]	47 1.5%	18 1.7%

63. Secondary Outcome

Title	Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCDs)
Description	NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.
Time Frame	From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3136	1044
Count of Participants [Participants]	163 5.2%	52 5%

64. Secondary Outcome

Title	Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCDs)
Description	NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.
Time Frame	From the fourth dose through the end of the 6-month safety follow-up

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Count of Participants [Participants]	85 2.7%	33 3.2%

65. Secondary Outcome

Title	Number of Subjects Reporting Rash
Description	Rash assessed was hives, idiopathic thrombocytopenic purpura, petechiae.
Time Frame	From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3136	1044
Count of Participants [Participants]	470 15%	154 14.8%

66. Secondary Outcome

Title	Number of Subjects Reporting Rash
Description	Rash assessed was hives, idiopathic thrombocytopenic purpura, petechiae.
Time Frame	From the fourth dose through the end of the 6-month safety follow-up

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Count of Participants [Participants]	265 8.5%	94 9%

67. Secondary Outcome

Title	Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits
Description	Emergency room (ER) visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.
Time Frame	From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3136	1044
Count of Participants [Participants]	217 6.9%	72 6.9%

68. Secondary Outcome

Title	Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits.
Description	Physicians (MD) office visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.
Time Frame	From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose

Outcome Measure Data

Analysis Population Description

The Primary Total Vaccinated cohort included all vaccinated subjects (Cohort 1, Cohort 2 & Cohort 3) in the primary phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	3136	1044
Count of Participants [Participants]	1336 42.6%	433 41.5%

69. Secondary Outcome

Title	Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits
Description	Emergency room (ER) visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.
Time Frame	From the fourth dose through the end of the 6-month safety follow-up

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Count of Participants [Participants]	137 4.4%	54 5.2%

70. Secondary Outcome

Title	Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits
Description	Physicians (MD) office visits were not related to well-child care, vaccination, injury or common acute illness such as upper respiratory tract infections; otitis media, pharyngitis, gastroenteritis.
Time Frame	From the fourth dose through the end of the 6-month safety follow-up

Outcome Measure Data

Analysis Population Description

The Fourth dose Total Vaccinated cohort included all vaccinated subjects in the fourth dose vaccination phase.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	2769	923
Count of Participants [Participants]	668 21.3%	205 19.6%

71. Secondary Outcome

Title	Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL).
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	341	112
Count of Participants [Participants]	227 7.2%	52 5%

72. Secondary Outcome

Title	Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titer Equal to or Above 1:8.
Description	This analysis occurred on the cohort 1: Cohort 1 was to include subjects in the US on which all immunogenicity analyses were to be based. These subjects also contributed to the safety analysis.
Time Frame	Prior to the fourth dose vaccination

Outcome Measure Data

Analysis Population Description

The Fourth dose ATP cohort for immunogenicity included all evaluable subjects (i.e. those who met eligibility criteria, complied with the procedures defined in the protocol, with no elimination criteria during the study) for whom results were available for antibodies against vaccine antigens for the blood sample taken 43 days post-vaccination.

Arm/Group Title	Menhibrix Group	ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.	Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
Measure Participants	329	104
hSBA-MenC [pre-dose 4]	318 10.1%	12 1.1%
hSBA-MenY [pre-dose 4]	306 9.8%	6 0.6%

Adverse Events

Time Frame	SAEs: From Day 0 after Dose 1 through the day preceding the fourth dose; From the fourth dose phase through the end of the safety follow-up; AEs: within the 31-day (Day 0-30) post vaccination period; Solicited AEs: Duting the 4-day post vaccination period
Adverse Event Reporting Description	Results are presented for the primary phase and the fourth dose phase.
Arm/Group Title	Menhibrix Group		ActHIB Group
Arm/Group Description	Subjects were primed with 3 doses of Menhibrix vaccine Lot A, B or C co-administered with Pediarix and boosted with 1 dose of Menhibrix vaccine, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. Menhibrix and Pediarix vaccines were administered intramuscularly in the right or left upper thigh, respectively. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.		Subjects were primed with 3 doses of ActHIB co-administered with Pediarix and boosted with 1 dose of PedvaxHIB, with co-administration of M-M-R II and Varivax. Subjects received vaccination at approximately 2, 4, 6 months and the fourth dose at 12-15 months of age. ActHIB, PedvaxHIB vaccines were administered intramuscularly in the right upper thigh and Pediarix vaccine in the left upper thigh. M-M-R II and Varivax vaccines were administered subcutaneously respectively in the upper left arm and the upper right arm.
All Cause Mortality
	Menhibrix Group		ActHIB Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Menhibrix Group		ActHIB Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	126/3136 (4%)		50/1044 (4.8%)
Blood and lymphatic system disorders
Lymphoid tissue hyperplasia	1/3136 (0%)		0/1044 (0%)
Idiopathic thrombocytopenic purpura	1/2769 (0%)		0/923 (0%)
Lymphadenitis	0/2769 (0%)		1/923 (0.1%)
Neutropenia	1/2769 (0%)		0/923 (0%)
Thrombocytopenia	1/2769 (0%)		0/923 (0%)
Congenital, familial and genetic disorders
Coarctation of the aorta	1/3136 (0%)		0/1044 (0%)
Tuberous sclerosis	1/3136 (0%)		0/1044 (0%)
Ventricular septal defect	1/3136 (0%)		0/1044 (0%)
Ventricular septal defect	0/2769 (0%)		1/923 (0.1%)
Eye disorders
Conjunctivitis	0/3136 (0%)		1/1044 (0.1%)
Dacryostenosis acquired	1/3136 (0%)		0/1044 (0%)
Gastrointestinal disorders
Intussusception	4/3136 (0.1%)		2/1044 (0.2%)
Vomiting	2/3136 (0.1%)		2/1044 (0.2%)
Abdominal pain	1/3136 (0%)		0/1044 (0%)
Gastrooesophageal reflux disease	1/3136 (0%)		0/1044 (0%)
Haematemesis	0/3136 (0%)		1/1044 (0.1%)
Hiatus hernia	0/3136 (0%)		1/1044 (0.1%)
Inguinal hernia	0/3136 (0%)		1/1044 (0.1%)
Abdominal pain	1/2769 (0%)		0/923 (0%)
Vomiting	1/2769 (0%)		0/923 (0%)
General disorders
Pyrexia	5/3136 (0.2%)		1/1044 (0.1%)
Irritability	1/3136 (0%)		0/1044 (0%)
Sudden infant death syndrome	1/3136 (0%)		0/1044 (0%)
Immune system disorders
Hypersensitivity	1/3136 (0%)		0/1044 (0%)
Hypersensitivity	1/2769 (0%)		0/923 (0%)
Infections and infestations
Gastroenteritis	19/3136 (0.6%)		7/1044 (0.7%)
Bronchiolitis	18/3136 (0.6%)		5/1044 (0.5%)
Otitis media	8/3136 (0.3%)		4/1044 (0.4%)
Viral infection	11/3136 (0.4%)		1/1044 (0.1%)
Gastroenteritis rotavirus	8/3136 (0.3%)		2/1044 (0.2%)
Pneumonia	8/3136 (0.3%)		2/1044 (0.2%)
Urinary tract infection	8/3136 (0.3%)		1/1044 (0.1%)
Respiratory syncytial virus infection	4/3136 (0.1%)		4/1044 (0.4%)
Croup infectious	2/3136 (0.1%)		3/1044 (0.3%)
Bronchopneumonia	1/3136 (0%)		3/1044 (0.3%)
Upper respiratory tract infection	4/3136 (0.1%)		0/1044 (0%)
Cellulitis	2/3136 (0.1%)		1/1044 (0.1%)
Viral upper respiratory tract infection	2/3136 (0.1%)		1/1044 (0.1%)
Pneumonia viral	2/3136 (0.1%)		0/1044 (0%)
Pyelonephritis	1/3136 (0%)		1/1044 (0.1%)
Viral skin infection	2/3136 (0.1%)		0/1044 (0%)
Abdominal wall abscess	0/3136 (0%)		1/1044 (0.1%)
Abscess	1/3136 (0%)		0/1044 (0%)
Acarodermatitis	1/3136 (0%)		0/1044 (0%)
Bronchitis viral	1/3136 (0%)		0/1044 (0%)
Campylobacter gastroenteritis	1/3136 (0%)		0/1044 (0%)
Escherichia urinary tract infection	1/3136 (0%)		0/1044 (0%)
Gastroenteritis adenovirus	0/3136 (0%)		1/1044 (0.1%)
Gastroenteritis viral	0/3136 (0%)		1/1044 (0.1%)
Group b streptococcus neonatal sepsis	1/3136 (0%)		0/1044 (0%)
HIV infection	1/3136 (0%)		0/1044 (0%)
Influenza	0/3136 (0%)		1/1044 (0.1%)
Lobar pneumonia	1/3136 (0%)		0/1044 (0%)
Meningitis viral	0/3136 (0%)		1/1044 (0.1%)
Nasopharyngitis	0/3136 (0%)		1/1044 (0.1%)
Pertussis	1/3136 (0%)		0/1044 (0%)
Sinusitis	0/3136 (0%)		1/1044 (0.1%)
Staphylococcal infection	1/3136 (0%)		0/1044 (0%)
Typhoid fever	0/3136 (0%)		1/1044 (0.1%)
Vulval abscess	1/3136 (0%)		0/1044 (0%)
Gastroenteritis	5/2769 (0.2%)		4/923 (0.4%)
Viral infection	5/2769 (0.2%)		0/923 (0%)
Croup infectious	4/2769 (0.1%)		0/923 (0%)
Bronchiolitis	2/2769 (0.1%)		0/923 (0%)
Otitis media	1/2769 (0%)		1/923 (0.1%)
Pneumonia viral	1/2769 (0%)		1/923 (0.1%)
Staphylococcal infection	2/2769 (0.1%)		0/923 (0%)
Abscess	1/2769 (0%)		0/923 (0%)
Abscess neck	1/2769 (0%)		0/923 (0%)
Adenoviral upper respiratory infection	0/2769 (0%)		1/923 (0.1%)
Cellulitis	1/2769 (0%)		0/923 (0%)
Cellulitis of male external genital organ	1/2769 (0%)		0/923 (0%)
Gastroenteritis rotavirus	1/2769 (0%)		0/923 (0%)
Gastroenteritis salmonella	0/2769 (0%)		1/923 (0.1%)
Gastroenteritis viral	1/2769 (0%)		0/923 (0%)
Lobar pneumonia	1/2769 (0%)		0/923 (0%)
Lower respiratory tract infection	0/2769 (0%)		1/923 (0.1%)
Lymph node abscess	0/2769 (0%)		1/923 (0.1%)
Osteomyelitis	0/2769 (0%)		1/923 (0.1%)
Pneumonia	1/2769 (0%)		0/923 (0%)
Pneumonia bacterial	0/2769 (0%)		1/923 (0.1%)
Respiratory tract infection viral	1/2769 (0%)		0/923 (0%)
Upper respiratory tract infection	1/2769 (0%)		0/923 (0%)
Urinary tract infection	1/2769 (0%)		0/923 (0%)
Viral upper respiratory tract infection	0/2769 (0%)		1/923 (0.1%)
Injury, poisoning and procedural complications
Respiratory syncytial virus bronchiolitis	8/3136 (0.3%)		2/1044 (0.2%)
Child maltreatment syndrome	1/3136 (0%)		0/1044 (0%)
Foreign body trauma	1/3136 (0%)		0/1044 (0%)
Head injury	1/3136 (0%)		0/1044 (0%)
Head injury	1/2769 (0%)		2/923 (0.2%)
Accidental drug intake by child	0/2769 (0%)		1/923 (0.1%)
Accidental exposure	1/2769 (0%)		0/923 (0%)
Burns first degree	1/2769 (0%)		0/923 (0%)
Burns second degree	1/2769 (0%)		0/923 (0%)
Multiple injuries	1/2769 (0%)		0/923 (0%)
Seroma	1/2769 (0%)		0/923 (0%)
Skin laceration	1/2769 (0%)		0/923 (0%)
Thermal burn	1/2769 (0%)		0/923 (0%)
Investigations
Aspiration bronchial	0/3136 (0%)		1/1044 (0.1%)
Metabolism and nutrition disorders
Dehydration	15/3136 (0.5%)		2/1044 (0.2%)
Failure to thrive	2/3136 (0.1%)		0/1044 (0%)
Acidosis	1/3136 (0%)		0/1044 (0%)
Dehydration	3/2769 (0.1%)		2/923 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemangioma	2/3136 (0.1%)		0/1044 (0%)
Neuroblastoma	1/3136 (0%)		0/1044 (0%)
Nervous system disorders
Febrile convulsion	2/3136 (0.1%)		2/1044 (0.2%)
Convulsion	2/3136 (0.1%)		1/1044 (0.1%)
Cerebellar ataxia	1/3136 (0%)		0/1044 (0%)
Hypotonia	1/3136 (0%)		0/1044 (0%)
Infantile spasms	1/3136 (0%)		0/1044 (0%)
Convulsion	2/2769 (0.1%)		1/923 (0.1%)
Febrile convulsion	1/2769 (0%)		0/923 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory distress	5/3136 (0.2%)		0/1044 (0%)
Asthma	3/3136 (0.1%)		1/1044 (0.1%)
Bronchial hyperreactivity	3/3136 (0.1%)		1/1044 (0.1%)
Hypoxia	3/3136 (0.1%)		1/1044 (0.1%)
Apparent life threatening event	2/3136 (0.1%)		0/1044 (0%)
Acute respiratory failure	0/3136 (0%)		1/1044 (0.1%)
Apnoea	1/3136 (0%)		0/1044 (0%)
Haemoptysis	1/3136 (0%)		0/1044 (0%)
Respiratory disorder	1/3136 (0%)		0/1044 (0%)
Stridor	1/3136 (0%)		0/1044 (0%)
Wheezing	1/3136 (0%)		0/1044 (0%)
Asthma	4/2769 (0.1%)		1/923 (0.1%)
Bronchial hyperreactivity	1/2769 (0%)		1/923 (0.1%)
Respiratory distress	1/2769 (0%)		1/923 (0.1%)
Wheezing	1/2769 (0%)		0/923 (0%)
Skin and subcutaneous tissue disorders
Erythema multiforme	1/3136 (0%)		0/1044 (0%)
Rash papular	1/2769 (0%)		0/923 (0%)
Urticaria	1/2769 (0%)		0/923 (0%)
Vascular disorders
Hypertension	1/3136 (0%)		0/1044 (0%)
Other (Not Including Serious) Adverse Events
	Menhibrix Group		ActHIB Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3034/3136 (96.7%)		998/1044 (95.6%)
Gastrointestinal disorders
Vomiting	197/3136 (6.3%)		65/1044 (6.2%)
Diarrhoea	185/3136 (5.9%)		57/1044 (5.5%)
Teething	180/3136 (5.7%)		55/1044 (5.3%)
Teething	115/2769 (4.2%)		46/923 (5%)
General disorders
Pyrexia	176/3136 (5.6%)		73/1044 (7%)
Pyrexia	176/2769 (6.4%)		64/923 (6.9%)
Pain	2419/3088 (78.3%)		819/1016 (80.6%)
Redness	2052/3088 (66.5%)		691/1016 (68%)
Swelling	1707/3088 (55.3%)		568/1016 (55.9%)
Drowsiness	2418/3088 (78.3%)		804/1015 (79.2%)
Fever	1434/3089 (46.4%)		463/1015 (45.6%)
Irritability	2740/3088 (88.7%)		926/1015 (91.2%)
Loss of appetite	1764/3088 (57.1%)		609/1015 (60%)
Pain	1319/2528 (52.2%)		494/832 (59.4%)
Redness	1213/2528 (48%)		463/833 (55.6%)
Swelling	936/2526 (37.1%)		334/832 (40.1%)
Increase in limb circumference	1489/2769 (53.8%)		503/923 (54.5%)
Drowsiness	1088/2526 (43.1%)		381/830 (45.9%)
Fever	341/2527 (13.5%)		134/831 (16.1%)
Irritability	1482/2526 (58.7%)		534/830 (64.3%)
Loss of appetite	825/2526 (32.7%)		287/830 (34.6%)
Infections and infestations
Upper respiratory tract infection	524/3136 (16.7%)		173/1044 (16.6%)
Otitis media	335/3136 (10.7%)		104/1044 (10%)
Upper respiratory tract infection	152/2769 (5.5%)		50/923 (5.4%)
Otitis media	135/2769 (4.9%)		47/923 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	163/3136 (5.2%)		50/1044 (4.8%)
Nasal congestion	146/3136 (4.7%)		53/1044 (5.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.