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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00129129
First received: August 10, 2005
Last updated: June 26, 2014
Last verified: June 2014
  Purpose

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

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


Condition Intervention Phase
Haemophilus Influenzae Type b
Neisseria Meningitidis
Biological: GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccine
Biological: ActHIB
Biological: Pediarix
Biological: Prevnar
Biological: Menomune
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: Evaluate Immuno and Safety of GSKBiologicals' HibMenCYTT vs Licensed Hib Conjugate Vaccine, Each Coadministered With Pediarix® and Prevnar®, in Healthy Infants. An Exploratory Control Group Will Receive Licensed Menomune® at 3 to 5 Years

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (≥) Cut-off Value. [ Time Frame: One month after the 3-dose primary vaccination course (at Month 5) ] [ Designated as safety issue: No ]
    The anti-PRP antibody cut-off value used for this outcome was 1.0 microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Concentration of Antibodies Against Streptococcus Pneumoniae Serotypes [ Time Frame: One month after the 3-dose primary vaccination course (at Month 5) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL). Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations [ Time Frame: One month after the 3-dose primary vaccination course (at Month 5) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting Any Grade 3 Symptoms [ Time Frame: During the 4-day follow-up period after each primary vaccine dose ] [ Designated as safety issue: No ]
    "Symptoms" were defined as solicited local and general symptoms and unsolicited adverse events (AEs). A "Grade 3" symptom was defined as any symptom that prevented normal everyday activity. "Any" was defined as an occurrence of any specified symptom regardless of intensity grade. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (≥) Cut-off Value [ Time Frame: One month after the fourth dose (at Month 11-14) ] [ Designated as safety issue: No ]
    The anti-PRP antibody cut-off value used for this outcome was 1.0 microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB/ActHIB groups .


Secondary Outcome Measures:
  • Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers ≥ the Cut-off Values [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    rSBA-MenC antibody cut-off values for this outcome were 1:8 and 1:128.

  • Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers ≥ the Cut-off Values [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    rSBA-MenY antibody cut-off values for this outcome measure were 1:8 and 1:128.

  • Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers ≥ 1:4 [ Time Frame: One month after the primary vaccination course (at Month 5 for the MenHibrix and ActHIB groups)/one month after vaccination (at Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    A composite outcome variable was formulated as follows for this immunogenicity analysis outcome: hSBA-Men titers ≥ 1:4 for subjects with post-vaccination rSBA-Men antibody titers ≥ 1:8 and lower than (<) 1:128.

  • Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers ≥ 1:4 [ Time Frame: One month after the primary vaccination course (at Month 5 for the MenHibrix and ActHIB groups)/one month after vaccination (at Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    A composite outcome variable was formulated as follows for this immunogenicity analysis outcome: hSBA-Men titers ≥ 1:4 for subjects with post-vaccination rSBA-Men antibody titers ≥ 1:8 and lower than (<) 1:128.

  • Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Above ≥ the Cut-off Values [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    Anti-PSC antibody cut-off values for this outcome were 0.3 µg/mL and 2.0 µg/mL.

  • Anti-polysaccharide C (Anti-PSC) Antibody Concentrations [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).

  • Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations Equal to or Above ≥ the Cut-off Values [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    Anti-PSY antibody cut-off values for this outcome were 0.3 µg/mL and 2.0 µg/mL.

  • Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5 for the MenHibrix and ActHIB groups)/ prior to and one month after vaccination (at Day 0 and Month 1 for the Menomune Group) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)

  • Number of Subjects Reporting Medically Attended Visits [ Time Frame: During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0 ] [ Designated as safety issue: No ]
    A medically attended visit was defined as an hospitalization, an emergency room visit or a visit to or from medical personnel. This Outcome Measure only concerns subjects in the Menomune Group.

  • Number of Subjects Reporting Rash [ Time Frame: During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0 ] [ Designated as safety issue: No ]
    An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae. This Outcome Measure only concerns subjects in the Menomune Group.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0 ] [ 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 subject . This Outcome Measure only concerns subjects in the Menomune Group.

  • Number of Subjects With Anti-PRP Antibody Concentrations ≥ the Cut-off Values [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    Anti-PRP antibody cut-off values for this outcome were 0.15 µg/mL and 1.0 µg/mL. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Anti-PRP Antibody Concentrations [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations ≥ Cut-off [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.05 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations ≥ Cut-off [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.2 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups

  • Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations ≥ Cut-off [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.5 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentration ≥ 0.1 International Units Per Milliliter (IU/mL) [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    The anti-diphtheria and anti-tetanus antibody cut-off value for this outcome was ≥ 0.1 IU/mL. This Outcome Measure only concerns the MenHibrix and ActHIB groups.

  • Anti-diphtheria and Anti-tetanus Antibody Concentrations [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as international units per milliliter (IU/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentration ≥ 10.0 Milli-international Units Per Milliliter (mIU/mL) [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentrations [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration ≥ 5.0 EL.U/mL [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Anti PT, Anti-FHA and Anti-PRN Antibody Concentrations [ Time Frame: Prior to the primary vaccination course (at Day 0) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as GMCs expressed as EL.U/mL. Results for one month after the 3-dose primary vaccination course (at Month 5) are presented under the Primary Outcome Measures section. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Anti-poliovirus Types 1, 2 and 3 Antibody Titer ≥ 1:8 [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Anti-poliovirus Types 1, 2 and 3 Antibody Titers [ Time Frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5) ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects With Vaccine Response to PT, FHA and PRN [ Time Frame: One month after the 3-dose primary vaccination course (at Month 5) ] [ Designated as safety issue: No ]
    Vaccine response to PT/FHA/PRN was defined as, for initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL one month post-primary vaccination course, and, for initially seropositive subjects, antibody concentration one month post-primary vaccination course ≥ 1-fold the pre-vaccination antibody concentration. A seronegative/seronegative subject was defined as a subject with antibody concentration </≥ 5 EL.U/mL for anti-PT/FHA/PRN prior to vaccination. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms [ Time Frame: Within 4 days (Day 0-3) after the 3-dose primary vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms were pain, redness and swelling at injection site. "Any" = any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling larger than (>) 10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling > 30 mm. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms [ Time Frame: Within 8 days (Day 0-7) after the 3-dose primary vaccination ] [ Designated as safety issue: No ]
    Solicited local symptoms were pain, redness and swelling at injection site. "Any" = any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling larger than (>) 10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling > 30 mm. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms [ Time Frame: Within 4 days (Day 0-3) after the 3-dose primary vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms were fever, irritability/fussiness, drowsiness, and loss of appetite. "Any" = any report of the specified symptom irrespective of intensity grade and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness and Loss of appetite = symptom that interfered with normal activity; "Grade 3" for Drowsiness and Irritability/Fussiness = symptom that prevented normal activity; "Grade 3" Loss of appetite = not eating at all. Fever = rectal temperature ≥ 38.0 degrees Celsius (°C); "Grade 2 or 3" fever = rectal temperature higher than (>) 39°C; "Grade 3" fever = rectal temperature > 40°C. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms [ Time Frame: Within 8 days (Day 0-7) after the 3-dose primary vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms were fever, irritability/fussiness, drowsiness, and loss of appetite. "Any" = any report of the specified symptom irrespective of intensity grade and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness and Loss of appetite = symptom that interfered with normal activity; "Grade 3" for Drowsiness and Irritability/Fussiness = symptom that prevented normal activity; "Grade 3" Loss of appetite = not eating at all. Fever = rectal temperature ≥ 38.0 degrees Celsius (°C); "Grade 2 or 3" fever = rectal temperature higher than (>) 39°C; "Grade 3" fever = rectal temperature > 40°C. This Outcome Measure only concerns the MenHibrix and ActHIB groups

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: From Dose 1 (at Day 0) through Day 30 following the last vaccine dose administered (Day 30 post Month 4 vaccination for MenHibrix and ActHIB groups, Day 30 post Month 1 for Menomune Group). ] [ Designated as safety issue: No ]
    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: During the entire Primary Phase of the study, from Day 0 up to the end of Primary Phase safety follow-up period (6 months after the last vaccination). ] [ 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 Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine. ] [ 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. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCIs) [ Time Frame: From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine ] [ Designated as safety issue: No ]
    NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting Rash [ Time Frame: From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine. ] [ Designated as safety issue: No ]
    An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

  • Number of Subjects Reporting Emergency Room (ER) Visits or Visits to Physicians' Office, Related or Not to Common Illnesses [ Time Frame: From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine. ] [ Designated as safety issue: No ]
    Emergency room (ER) visits or physicians office visits assessed were those unrelated to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infections, otitis media, pharyngitis, gastroenteritis. This Outcome Measure only concerns the MenHibrix and ActHIB groups.

  • Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC and Y) [ Time Frame: One month post fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Fourth dose responses to rSBA-MenC and rSBA-MenY were defined as follows (Definition 1):

    • Initially seronegative subjects (pre-fourth dose antibody titer below cut-off: < 1:8) should have an antibody titer at least four-fold higher than the cut-off, one month after fourth dose (post-fourth dose antibody titer ≥1:32),
    • Initially seropositive subjects (pre-fourth dose antibody titer above cut-off: ≥1:8) should have an antibody titer at least four-fold higher than the pre-fourth dose antibody titer, one month after fourth dose.

  • Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC and Y) [ Time Frame: One month post fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Fourth dose responses to rSBA-MenC and rSBA-MenY were also assessed using a second definition (Definition 2):

    • Post-fourth dose rSBA antibody titers ≥1:32 in subjects seronegative at the pre-fourth dose time point (rSBA antibody titers < 1:8),
    • At least (i.e., greater than or equal to) a 4-fold rise in rSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:8 but < 1:128,
    • At least (i.e., greater than or equal to) a 2-fold rise in rSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:128.

  • Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Human Complement (hSBA-MenC and Y) [ Time Frame: One month post fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Fourth dose responses to hSBA-MenC and hSBA-MenY were defined as follows (Definition 1):

    • Initially seronegative subjects (pre-fourth dose antibody titer below cut-off: < 1:8) should have an antibody titer at least four-fold higher than the cut-off, one month after the fourth dose (post-fourth dose antibody titer ≥1:16),
    • Initially seropositive subjects (pre-fourth dose antibody titer above cut-off: ≥1:8) should have an antibody titer at least four-fold higher than the pre-fourth dose antibody titer, one month after the fourth dose.

  • Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Human Complement (hSBA-MenC and Y) [ Time Frame: One month post fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Fourth dose responses to hSBA-MenC and hSBA-MenY were also assessed using a second definition (Definition 2):

    • Post-fourth dose hSBA antibody titers ≥1:16 in subjects seronegative at the pre-fourth dose time point (hSBA antibody titers < 1:8),
    • At least (i.e., greater than or equal to) a 4-fold rise in hSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:4 but < 1: 8,
    • At least (i.e., greater than or equal to) a 2-fold rise in hSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:8.

  • Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.05 Microgram Per Milliliter (µg/mL) [ Time Frame: One month after fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Streptococcus pneumoniae antibody cut-off values assessed was ≥0.05 µg/mL for the 7 serotypes in Prevnar vaccine.

    Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.


  • Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.2 Microgram Per Milliliter (µg/mL) [ Time Frame: One month after fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Streptococcus pneumoniae antibody cut-off values assessed was ≥0.2 µg/mL for the 7 serotypes in Prevnar vaccine.

    Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.


  • Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.5 Microgram Per Milliliter (µg/mL) [ Time Frame: One month after fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Streptococcus pneumoniae antibody cut-off values assessed was ≥0.5 µg/mL for the 7 serotypes in Prevnar vaccine.

    Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.


  • Concentration of Antibodies Against Streptococcus Pneumonia Serotypes [ Time Frame: One month post fourth dose vaccination (at Month 11-14) ] [ Designated as safety issue: No ]

    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).

    Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.


  • Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Anti-PRP antibody cut-off values assessed were ≥0.15 µg/mL and ≥1.0 µg/mL.

  • Anti-PRP Antibody Concentrations [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)

  • Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers Equal to or Above the Cut-off Values [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    rSBA-MenC antibody cut-off values assessed were ≥1:8 and ≥1:128

  • rSBA-MenC Antibody Titers [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers Equal to or Above the Cut-off Values [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    rSBA-MenY antibody cut-off values assesse were ≥1:8 and ≥1:128.

  • rSBA-MenY Antibody Titers [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers Equal to or Above the Cut-off Values [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    hSBA-MenC antibody cut-off values assessed were ≥1:4 and ≥1:8.

  • hSBA-MenC Antibody Titers [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Human Complement (hSBA-MenY) Antibody Titers Equal to or Above the Cut-off Values [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    hSBA-MenY antibody cut-off values assessed were ≥1:4 and ≥1:8.

  • hSBA-MenY Antibody Titers [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Titers are presented as geometric mean titers (GMTs).

  • Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Anti-PSC antibody cut-off values assessed were ≥0.3 µg/mL and ≥2.0 µg/mL.

  • Anti-PSC Antibody Concentrations [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).

  • Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Anti-PSY antibody cut-off values assessed were ≥0.3 µg/mL and ≥2.0 µg/mL.

  • Anti-PSY Antibody Concentrations [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)

  • Number of Subjects With Anti-tetanus Antibody Concentration Equal to or Above 0.1 International Units Per Milliliter (IU/mL) [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
  • Anti-tetanus Antibody Concentrations [ Time Frame: Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14) ] [ Designated as safety issue: No ]
    Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as international units per milliliter (IU/mL).

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms [ Time Frame: Within 4 days (Day 0-3) after fourth dose vaccination ] [ Designated as safety issue: No ]
    Solicited symptoms assessed were pain, redness, swelling at the injection site and increase in limb circumference. "Any"= any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling >10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling >30 mm; "Grade 2" limb circumference (LC) = LC >20 mm; "Grade 3" LC = LC >40 mm

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms [ Time Frame: Within 8 days (Day 0-7) after fourth dose vaccination ] [ Designated as safety issue: No ]
    Solicited symptoms assessed were pain, redness, swelling at the injection site and increase in limb circumference. "Any"= any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling >10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling >30 mm; "Grade 2" limb circumference (LC) = LC >20 mm; "Grade 3" LC = LC >40 mm

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms [ Time Frame: Within 4 days (Day 0-3) after fourth dose vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were fever, irritability/fussiness, drowsiness, loss of appetite. "Any"= any report of the specified symptom irrespective of intensity and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness & Loss of appetite = interfered with normal activity; "Grade 3" for Drowsiness, Irritability/Fussiness = prevented normal activity; "Grade 3" Loss of appetite = not eating at all; Fever = rectal temperature (T) ≥38.0 degrees Celsius (°C); "Grade 2 or 3" for fever = T >39.0°C; "Grade 3" for fever = T >40.0°C

  • Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms [ Time Frame: Within 8 days (Day 0-7) after fourth dose vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were fever, irritability/fussiness, drowsiness, loss of appetite. "Any"= any report of the specified symptom irrespective of intensity and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness & Loss of appetite = interfered with normal activity; "Grade 3" for Drowsiness, Irritability/Fussiness = prevented normal activity; "Grade 3" Loss of appetite = not eating at all; Fever = rectal temperature (T) ≥38.0 degrees Celsius (°C); "Grade 2 or 3" for fever = T >39.0°C; "Grade 3" for fever = T >40.0°C

  • Number of Subjects Reporting Unsolicited Adverse Events (AEs) [ Time Frame: During the 31-day follow-up period following the fourth dose ] [ Designated as safety issue: No ]
    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

  • Number of Subjects Reporting New Onset of Chronic Illness(es) [ Time Frame: From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.

  • Number of Subjects Reporting Rash [ Time Frame: From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae.

  • Number of Subjects Reporting Emergency Room (ER) Visits or Physicians Office Visits Related or Not to Common Illnesses [ Time Frame: From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up ] [ Designated as safety issue: No ]
    Emergency room (ER) visits or physicians office visits assessed were those unrelated to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infections, otitis media, pharyngitis, gastroenteritis. This Outcome Measure only concerns the MenHibrix and ActHIB groups.

  • Number of Subjects Reporting Large Swelling Reactions of the Injected Limb(s) [ Time Frame: Within 4 days (Day 0-3) and within 8 days (Day 0-7) following the fourth dose ] [ Designated as safety issue: No ]
    Large injection site reactions were defined as either swelling with a diameter of > 30 mm or a > 30 mm increase in the circumference of the mid-thigh when compared to the baseline (pre-vaccination) measurement, or any diffuse swelling that interfered with or prevented everyday activities (for example, active playing, eating, sleeping).


Enrollment: 756
Study Start Date: August 2004
Study Completion Date: March 2006
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MenHibrix Group
Subjects in the Group were followed during the entire study period, from Day 0 up to study end 6 months post fourth dose vaccinationDuring Primary Phase (Study 101858), subjects in this group, aged 6-12 weeks at enrolment, received 3 doses of Menhibrix™ co-administered with Pediarix™ and Prevnar™ (at Day 0 and Months 2 and 4). During Fourth-Dose Phase (Study 102015), subjects primed with 3 doses of Menhibrix™ during the Primary Phase received one dose of Menhibrix™ and one concomitant dose of Prevnar™ at Month 10-13. During Primary Phase, Menhibrix™ was administered intramuscularly (IM) in the right upper thigh, and Pediarix™ and Prevnar™ IM in the left upper and lower thighs, respectively. During Fourth-Dose Phase, Menhibrix™ was administered by the same route and at the same site as during Primary Phase, and Prevnar™ was administered IM in the left upper thigh.
Biological: GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccine
Primary phase: 3 IM doses Booster phase: 1 IM dose
Biological: Pediarix
Primary phase: 3 IM doses
Biological: Prevnar
Primary phase: 3 IM doses Booster phase: 1 IM dose
Active Comparator: ActHIB Group
During Primary Phase (Study 101858), subjects in this group, aged 6-12 weeks at enrolment, received 3 doses of ActHIB™ vaccine co-administered with the Pediarix™ and Prevnar™ vaccines (at Day 0 and Months 2 and 4). Subjects in this Group were followed from Day 0 up to Month 10-13 solely. During Fourth-Dose Phase (Study 102015), these subjects were followed as subjects either in the ActHIB/MenHibrix Group or in the ActHIB/ActHIB Group, receiving then one dose of either Menhibrix™ or ActHIB™ concomitantly with one dose of Prevnar™. During Primary Phase, ActHIB™ was administered intramuscularly (IM) in the right upper thigh, and the Pediarix™ and Prevnar™ vaccines IM in the left upper and lower thighs, respectively.
Biological: ActHIB
Primary phase: 3 IM doses Booster phase: 1 IM dose
Biological: Pediarix
Primary phase: 3 IM doses
Biological: Prevnar
Primary phase: 3 IM doses Booster phase: 1 IM dose
Active Comparator: Menomune Group
Subjects in the Group were followed solely during the period of Primary Phase (Study 101858), up to Month 10. Subjects in the Group, aged 3-5 years at enrolment, received one dose of Menomune™ at Day 0. Menomune™ was administered subcutaneously in the left deltoid region.
Biological: Pediarix
Primary phase: 3 IM doses
Biological: Prevnar
Primary phase: 3 IM doses Booster phase: 1 IM dose
Biological: Menomune
Primary phase: 1 SC dose
Experimental: ActHIB/Menhibrix Group
Subjects in the Group were followed solely during the period of the Fourth-Dose Phase of the study (Study 102015), from Month 10-13 to Month 11-14. Subjects in this Group had been primed with ActHIB™ during Primary Phase (study 101858) and received at Month 10-13 a fourth dose of Menhibrix™ and a concomitant fourth dose of Prevnar™. Menhibrix™ and Prevnar™ were administered intramuscularly in the right and left upper thighs, respectively.
Biological: GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccine
Primary phase: 3 IM doses Booster phase: 1 IM dose
Biological: ActHIB
Primary phase: 3 IM doses Booster phase: 1 IM dose
Biological: Pediarix
Primary phase: 3 IM doses
Biological: Prevnar
Primary phase: 3 IM doses Booster phase: 1 IM dose
Experimental: ActHIB/ActHIB Group
Subjects in the Group were followed solely during the period of the Fourth-Dose Phase of the study (Study 102015), from Month 10-13 to Month 11-14. Subjects in this Group had been primed with ActHIB™ during Primary Phase of the study (study 101858) and received at Month 10-13 a fourth dose of ActHIB™ and a concomitant fourth dose of Prevnar™. ActHIB™ and Prevnar™ were administered intramuscularly in the right and left upper thighs, respectively.
Biological: ActHIB
Primary phase: 3 IM doses Booster phase: 1 IM dose
Biological: Pediarix
Primary phase: 3 IM doses
Biological: Prevnar
Primary phase: 3 IM doses Booster phase: 1 IM dose

Detailed Description:

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

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

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

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

  Eligibility

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

Inclusion Criteria:

  • For Groups A and B

    • Subjects for whom the investigator believes that parents/guardians can and will comply with the requirements of the protocol.
    • Healthy male or female between, and including, 6 and 12 weeks of age at the time of the first vaccination.
    • Written informed consent obtained from the parent or guardian of the subject.
    • Free of obvious health problems as established by medical history and clinical examination before entering the study.
    • Born after a gestation period between 36 and 42 weeks.
    • Infants who have not received a previous dose of hepatitis B vaccine or those who have received only 1 dose of hepatitis B vaccine administered at least 30 days prior to enrollment.
  • For Group C

    • Subjects for whom the investigator believes that parents/guardians can and will comply with the requirements of the protocol.
    • Healthy male or female between, and including, 3 and 5 years of age at the time of the first vaccination.
    • Written informed consent obtained from the parent or guardian of the subject.
    • Free of obvious health problems as established by medical history and clinical examination before entering the study.

Exclusion Criteria:

-For Groups A and B

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
  • Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine(s).
  • Previous vaccination against Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, poliovirus, and/or Streptococcus pneumoniae; more than one previous dose of hepatitis B vaccine.
  • History of Neisseria meningitidis, Haemophilus influenzae type b, diphtheria, tetanus, pertussis, hepatitis B, poliovirus, and/or Streptococcus pneumoniae disease.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s), including dry natural latex rubber.
  • Major congenital defects or serious chronic illness.
  • History of any neurologic disorders or seizures.
  • Acute disease at time of enrollment.
  • Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

For Group C

  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the vaccine dose.
  • Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the dose of study vaccine.
  • Previous vaccination against Neisseria meningitidis.
  • History of Neisseria meningitidis disease.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, including dry natural latex rubber
  • Major congenital defects or serious chronic illness.
  • Acute disease at time of enrollment.
  • Administration of immunoglobulins and/or any blood products within the 3 months preceding vaccination or planned administration during the study period.
  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: NCT00129129

  Show 27 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00129129     History of Changes
Other Study ID Numbers: 101858, 102015
Study First Received: August 10, 2005
Results First Received: June 15, 2012
Last Updated: June 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Immunogenicity
Primary & booster vaccination
Infants
Meningococcal vaccine
Safety
Children
Hib disease
Meningococcal disease

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 14, 2014