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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00289783
First received: February 9, 2006
Last updated: October 18, 2012
Last verified: October 2012
  Purpose

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 Intervention Phase
Meningococcal Infection
Haemophilus Influenzae Type b Infection
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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Anti-Polyribosyl Ribitol Phosphate (PRP) Antibody Concentrations [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • Neisseria Meningitidis Serogroup C (MenC) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • Neisseria Meningitidis Serogroup Y (MenY) Serum Bactericidal Assay Using Human Complement (hSBA) Antibody Titers [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • hSBA-MenC Antibody Titers [ Time Frame: Prior to the fourth dose vaccination and 42 days after the fourth dose ] [ Designated as safety issue: No ]

    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.


  • hSBA-MenY Antibody Titers [ Time Frame: Prior to the fourth dose vaccination and 42 days after the fourth dose ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL) [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With hSBA-MenC Titer Equal to or Above 1:8 [ Time Frame: 42 days after the fourth dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With hSBA-MenY Titer Equal to or Above 1:8 [ Time Frame: 42 days after the fourth dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter [ Time Frame: 42 days after the fourth dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 150 Milli-international Units Per Milli-liter (mIU/ML) [ Time Frame: 42 days after the fourth dose ] [ Designated as safety issue: No ]

    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


  • Number of Subjects With Anti-mumps Titer Equal to or Above 28 Estimated Dose 50 (ED50) [ Time Frame: 42 days after the fourth dose ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 10 International Units Per Milli-litre (IU/mL) [ Time Frame: 42 days after the fourth dose ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-varicella Titer Equal to or Above 1:5 [ Time Frame: 42 days after the fourth dose ] [ Designated as safety issue: No ]

    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:
  • 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) [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]
    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.

  • Anti-D and Anti-T Antibody Concentrations [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • 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) [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-HBS Antibody Concentrations [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • 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) [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]
    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.

  • Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Anti-poliovirus Types 1, 2 and 3 Equal to or Above 8 Estimated Dose 50 (ED50) [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]
    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.

  • Anti-poliovirus Types 1, 2 and 3 Titers [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • 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 [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-PSC and Anti-PSY Antibody Concentrations [ Time Frame: One month after primary vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: Prior to the fourth dose vaccination and one month after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-PRP Antibody Concentrations [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • Anti-PRP Antibody Concentrations [ Time Frame: Prior to the fourth dose vaccination and one month after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With hSBA-MenC and hSBA-MenY Titers Equal to or Above the Cut-off Values [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With hSBA-MenC and hSBA-MenY Titers Equal to or Above the Cut-off Values [ Time Frame: Prior to the fourth dose vaccination and one month after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • hSBA-MenC and hSBA-MenY Antibody Titers [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • hSBA-MenC and hSBA-MenY Antibody Titers [ Time Frame: Prior to the fourth dose vaccination and one month after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: Prior to the fourth dose vaccination and one month after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-PSC and Anti-PSY Antibodies Concentrations [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • Anti-PSC and Anti-PSY Antibody Concentrations [ Time Frame: Prior to the fourth dose vaccination and one month after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above the Cut-off Value [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • Anti-PRP Antibody Concentrations [ Time Frame: One month after the primary vaccination course and prior to the fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titers Equal to or Above the Cut-off Values [ Time Frame: One month after the primary vaccination course ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PSC and Anti-PSY Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: Prior to the fourth dose vaccination and 42 days after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-PSC and Anti-PSY Antibody Concentrations [ Time Frame: Prior to the fourth dose vaccination and 42 days after fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-PRP Antibody Concentrations Equal to or Above 0.15 Microgram Per Milliliter (µg/mL) [ Time Frame: Prior to the fourth dose vaccination and 42 days after fourth vaccination ] [ Designated as safety issue: No ]
    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.

  • Anti-PRP Antibody Concentrations [ Time Frame: Prior to the fourth vaccination and 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Concentrations Equal to or Above 1:4 [ Time Frame: Prior to the fourth dose vaccination and 42 days after fourth vaccination ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Anti-measles Antibody Concentrations Equal to or Above 200 Milli-international Units Per Millilitre (mIU/mL) [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-measles Antibody Concentrations [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-mumps Titer Equal to or Above the Cut-off Values [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-mumps Antibody Titers [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-rubella Antibody Concentrations Equal to or Above 4 International Units Per Millilitre (IU/mL) [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-rubella Antibody Concentrations [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-varicella Titer Equal to or Above 1:40 [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Anti-varicella Antibody Titers [ Time Frame: 42 days after fourth vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects With Anti-H1N1, Anti-H3N2 and Anti-influenza-B (Anti B) Antibody Titers Equal to or Above 1:40 [ Time Frame: Prior to the fourth dose vaccination and one month after the fourth dose vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Subjects Reporting Fever Above 39.5 Degrees Celsius/103.1 Degrees Fahrenheit [ Time Frame: In the 4-day (Day 0-3) follow-up period after primary vaccination course ] [ Designated as safety issue: No ]
    Fever is defined as temperature (rectal or axillary/tympanic) above 39.5 degrees Celsius (°C) or 103.1 degrees Fahrenheit (°F).

  • Number of Subjects Reporting Fever Above 39.5 Degrees Celsius/103.1 Degrees Fahrenheit [ Time Frame: In the 4-day (Day0-3) follow-up period after the fourth dose ] [ Designated as safety issue: No ]
    Fever is defined as temperature (rectal or axillary/tympanic) above 39.5 degrees Celsius (°C) or 103.1 degrees Fahrenheit (°F).

  • Number of Subjects Reporting Solicited Local and General Symptoms [ Time Frame: Within the 4 days (Day 0-3) following the primary vaccination course ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Solicited Local and General Symptoms [ Time Frame: Within the 4 days (Day 0-3) post-vaccination period following the fourth dose ] [ Designated as safety issue: No ]
    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

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: Within 31 days (Day 0-30) following the primary vaccination course ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: Within 31 days (Day 0-30) following the fourth dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Increased Circumferential Swelling at the Injection Limb(s) [ Time Frame: Within 4 days (Day 0 to Day 3) after fourth dose vaccination ] [ Designated as safety issue: No ]
    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).

  • Number of Subjects Reporting General Symptoms Specific to Measles, Mumps, Rubella and Varicella Vaccination [ Time Frame: Within 43 days (Day 0 through Day 42) after vaccination ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: From Dose 0 through 6 months after the last primary dose or untill administration of the fourth dose ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: From the fourth dose through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects.

  • Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCDs) [ Time Frame: From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose ] [ Designated as safety issue: No ]
    NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.

  • Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCDs) [ Time Frame: From the fourth dose through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.

  • Number of Subjects Reporting Rash [ Time Frame: From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose ] [ Designated as safety issue: No ]
    Rash assessed was hives, idiopathic thrombocytopenic purpura, petechiae.

  • Number of Subjects Reporting Rash [ Time Frame: From the fourth dose through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    Rash assessed was hives, idiopathic thrombocytopenic purpura, petechiae.

  • Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits [ Time Frame: From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits. [ Time Frame: From Dose 0 through 6 months after the last primary dose or until administration of the fourth dose ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Adverse Events Resulting in Emergency Room (ER) Visits [ Time Frame: From the fourth dose through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects Reporting Adverse Events Resulting in Physicians (MD) Office Visits [ Time Frame: From the fourth dose through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Anti-PRP Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL). [ Time Frame: Prior to the fourth dose vaccination ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With hSBA-MenC and hSBA-MenY Antibody Titer Equal to or Above 1:8. [ Time Frame: Prior to the fourth dose vaccination ] [ Designated as safety issue: No ]
    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.


Enrollment: 4441
Study Start Date: February 2006
Study Completion Date: August 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   6 Weeks to 15 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00289783

  Show 83 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Bryant KA et al. (2011) Immunogenicity and Safety of H influenzae Type b-N meningitidis C/Y Conjugate Vaccine in Infants. Pediatrics. 127(6):1375-1385.
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00289783     History of Changes
Other Study ID Numbers: 103813, 105067
Study First Received: February 9, 2006
Results First Received: June 15, 2012
Last Updated: October 18, 2012
Health Authority: United States: Food and Drug Administration

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
Meningococcal Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on August 28, 2014