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

Phase 2

Completed

• Conditions: Haemophilus Influenzae Type b; Neisseria Meningitidis
• Interventions: Biological: GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccine; Biological: Pediarix; Biological: ActHIB; Biological: Menomune; Biological: Prevnar

• Registration Number: NCT00129129
• Lead Sponsor: GlaxoSmithKline

Brief Summary

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

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

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.

Study Timeline

• Study Start: 2004-08-01
• Study First Submitted: 2005-08-10
• Study First Submitted QC: 2005-08-10
• Study First Posted: 2005-08-11
• Primary Completion: 2005-09-15
• Study Completion: 2006-03-29
• Results First Submitted: 2012-06-15
• Results First Submitted QC: 2013-12-05
• Results First Posted: 2013-12-30
• Status Verified: 2016-09
• Last Update Submitted: 2018-07-26
• Last Update Posted: 2018-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 756

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MenHibrix Group	Pediarix	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.
Menomune Group	Menomune	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.
ActHIB Group	Pediarix	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.
ActHIB Group	Prevnar	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.
Menomune Group	Pediarix	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.
MenHibrix Group	Prevnar	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.
ActHIB/Menhibrix Group	Prevnar	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.
ActHIB/ActHIB Group	Pediarix	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.
MenHibrix Group	GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccine	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.
Menomune Group	Prevnar	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.
ActHIB/Menhibrix Group	ActHIB	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.
ActHIB/ActHIB Group	Prevnar	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.
ActHIB Group	ActHIB	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.
ActHIB/Menhibrix Group	GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccine	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.
ActHIB/Menhibrix Group	Pediarix	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.
ActHIB/ActHIB Group	ActHIB	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.

Primary Outcome Measures

Name	Time	Method
Concentration of Antibodies Against Streptococcus Pneumoniae Serotypes	One month after the 3-dose primary vaccination course (at Month 5)	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	One month after the 3-dose primary vaccination course (at Month 5)	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 With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (≥) Cut-off Value.	One month after the 3-dose primary vaccination course (at Month 5)	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 .
Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (≥) Cut-off Value	One month after the fourth dose (at Month 11-14)	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 .
Number of Subjects Reporting Any Grade 3 Symptoms	During the 4-day follow-up period after each primary vaccine dose	"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 .

Secondary Outcome Measures

Name	Time	Method
Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers	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)	Titers are presented as geometric mean titers (GMTs).
Number of Subjects Reporting Medically Attended Visits	During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0	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 Serious Adverse Events (SAEs)	From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.	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 .
Anti-polysaccharide C (Anti-PSC) Antibody Concentrations	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)	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).
Anti-PRP Antibody Concentrations	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)
Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations ≥ Cut-off	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	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 Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers ≥ the Cut-off Values	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)	rSBA-MenC antibody cut-off values for this outcome were 1:8 and 1:128.
Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers ≥ the Cut-off Values	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)	rSBA-MenY antibody cut-off values for this outcome measure were 1:8 and 1:128.
Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers ≥ 1:4	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)	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	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)	Anti-PSC antibody cut-off values for this outcome were 0.3 µg/mL and 2.0 µg/mL.
Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations Equal to or Above ≥ the Cut-off Values	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)	Anti-PSY antibody cut-off values for this outcome were 0.3 µg/mL and 2.0 µg/mL.
Anti-diphtheria and Anti-tetanus Antibody Concentrations	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	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 .
Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenY) Antibody Titers	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)	Titers are presented as geometric mean titers (GMTs).
Number of Subjects With Neisseria Meningitidis Serogroup Y Serum Bacterial Assay Using Human Complement (hSBA-MenC) Antibody Titers ≥ 1:4	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)	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.
Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations	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)	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)
Number of Subjects Reporting Rash	From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up	An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae.
Number of Subjects With Anti-PRP Antibody Concentrations ≥ the Cut-off Values	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	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 .
Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentration ≥ 0.1 International Units Per Milliliter (IU/mL)	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	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.
Number of Subjects With Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentration ≥ 10.0 Milli-international Units Per Milliliter (mIU/mL)	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	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	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	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	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	This Outcome Measure only concerns the MenHibrix and ActHIB groups .
Anti-poliovirus Types 1, 2 and 3 Antibody Titers	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	Titers are presented as geometric mean titers (GMTs). 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	Within 8 days (Day 0-7) after fourth dose vaccination	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 New Onset of Chronic Illness(es) (NOCIs)	From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine	NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. 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 Human Complement (hSBA-MenC and Y)	One month post fourth dose vaccination (at Month 11-14)	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)	One month after fourth dose vaccination (at Month 11-14)	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.
Concentration of Antibodies Against Streptococcus Pneumonia Serotypes	One month post fourth dose vaccination (at Month 11-14)	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.
rSBA-MenC Antibody Titers	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	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	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	hSBA-MenC antibody cut-off values assessed were ≥1:4 and ≥1:8.
Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentrations	Prior to and one month after the primary vaccination course (at Day 0 and Month 5)	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 .
Anti PT, Anti-FHA and Anti-PRN Antibody Concentrations	Prior to the primary vaccination course (at Day 0)	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 Reporting Emergency Room (ER) Visits or Visits to Physicians' Office, Related or Not to Common Illnesses	From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.	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)	One month post fourth dose vaccination (at Month 11-14)	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 Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.2 Microgram Per Milliliter (µg/mL)	One month after fourth dose vaccination (at Month 11-14)	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.
Anti-PSY Antibody Concentrations	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL)
Number of Subjects Reporting Large Swelling Reactions of the Injected Limb(s)	Within 4 days (Day 0-3) and within 8 days (Day 0-7) following the fourth dose	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).
Number of Subjects With Vaccine Response to PT, FHA and PRN	One month after the 3-dose primary vaccination course (at Month 5)	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 General Symptoms	Within 8 days (Day 0-7) after fourth dose vaccination	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)	During the 31-day follow-up period following the fourth dose	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 With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers Equal to or Above the Cut-off Values	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	rSBA-MenC antibody cut-off values assessed were ≥1:8 and ≥1:128
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	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	rSBA-MenY antibody cut-off values assesse were ≥1:8 and ≥1:128.
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	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	hSBA-MenY antibody cut-off values assessed were ≥1:4 and ≥1:8.
Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Equal to or Above the Cut-off Values	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Anti-PSC antibody cut-off values assessed were ≥0.3 µg/mL and ≥2.0 µg/mL.
Number of Subjects With Anti-polysaccharide Y (Anti-PSY) Antibody Concentrations Equal to or Above the Cut-off Values	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Anti-PSY antibody cut-off values assessed were ≥0.3 µg/mL and ≥2.0 µg/mL.
Number of Subjects Reporting New Onset of Chronic Illness(es)	From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up	NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.
Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.5 Microgram Per Milliliter (µg/mL)	One month after fourth dose vaccination (at Month 11-14)	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.
Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations Equal to or Above the Cut-off Values	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Anti-PRP antibody cut-off values assessed were ≥0.15 µg/mL and ≥1.0 µg/mL.
rSBA-MenY Antibody Titers	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Titers are presented as geometric mean titers (GMTs).
Anti-PSC Antibody Concentrations	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).
hSBA-MenC Antibody Titers	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Titers are presented as geometric mean titers (GMTs).
hSBA-MenY Antibody Titers	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Titers are presented as geometric mean titers (GMTs).
Number of Subjects With Anti-tetanus Antibody Concentration Equal to or Above 0.1 International Units Per Milliliter (IU/mL)	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)
Anti-tetanus Antibody Concentrations	Prior to and one month after the fourth dose (at Month 10-13 and at Month 11-14)	Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as international units per milliliter (IU/mL).
Number of Subjects Reporting Emergency Room (ER) Visits or Physicians Office Visits Related or Not to Common Illnesses	From receipt of the fourth dose (at Month 10-13) through the end of the 6-month safety follow-up	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇺🇸 Warwick, Rhode Island, United States