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

GlaxoSmithKline756 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

756

Conditions

Haemophilus Influenzae Type b

Interventions

GSK Biologicals' Haemophilus influenza type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine 792014 vaccineBIOLOGICAL

Primary phase: 3 IM doses Booster phase: 1 IM dose

ActHIBBIOLOGICAL

Primary phase: 3 IM doses Booster phase: 1 IM dose

PediarixBIOLOGICAL

Primary phase: 3 IM doses

PrevnarBIOLOGICAL

Primary phase: 3 IM doses Booster phase: 1 IM dose

MenomuneBIOLOGICAL

Primary phase: 1 SC dose

Eligibility

Sex: ALLMin age: 6 WeeksMax age: 15 MonthsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (27)

GSK Investigational Site

Little Rock, Arkansas, United States

GSK Investigational Site

Fountain Valley, California, United States

GSK Investigational Site

Centennial, Colorado, United States

GSK Investigational Site

Norwich, Connecticut, United States

GSK Investigational Site

Marietta, Georgia, United States

GSK Investigational Site

Des Moines, Iowa, United States

GSK Investigational Site

Bardstown, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Bossier City, Louisiana, United States

...and 17 more locations

Outcomes

Primary Outcomes

Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (≥) Cut-off Value.

The anti-PRP antibody cut-off value used for this outcome was 1.0 microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: One month after the 3-dose primary vaccination course (at Month 5)

Concentration of Antibodies Against Streptococcus Pneumoniae Serotypes

Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL). Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: One month after the 3-dose primary vaccination course (at Month 5)

Anti-pertussis Toxoid (PT), Anti-filamentous Haemagglutinin (FHA) and Anti-pertactin (PRN) Antibody Concentrations

Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed in Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: One month after the 3-dose primary vaccination course (at Month 5)

Number of Subjects Reporting Any Grade 3 Symptoms

"Symptoms" were defined as solicited local and general symptoms and unsolicited adverse events (AEs). A "Grade 3" symptom was defined as any symptom that prevented normal everyday activity. "Any" was defined as an occurrence of any specified symptom regardless of intensity grade. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: During the 4-day follow-up period after each primary vaccine dose

Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentration Equal to or Above (≥) Cut-off Value

The anti-PRP antibody cut-off value used for this outcome was 1.0 microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB/ActHIB groups .

Time frame: One month after the fourth dose (at Month 11-14)

Secondary Outcomes

Number of Subjects With Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers ≥ the Cut-off Values

rSBA-MenC antibody cut-off values for this outcome were 1:8 and 1:128.

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)

Neisseria Meningitidis Serogroup C Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC) Antibody Titers

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

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

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

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.

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)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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)

Number of Subjects With Anti-polysaccharide C (Anti-PSC) Antibody Concentrations Above ≥ the Cut-off Values

Anti-PSC antibody cut-off values for this outcome were 0.3 µg/mL and 2.0 µg/mL.

Anti-polysaccharide C (Anti-PSC) Antibody Concentrations

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

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

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

Number of Subjects Reporting Medically Attended Visits

A medically attended visit was defined as an hospitalization, an emergency room visit or a visit to or from medical personnel. This Outcome Measure only concerns subjects in the Menomune Group.

Time frame: During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0

Number of Subjects Reporting Rash

An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae. This Outcome Measure only concerns subjects in the Menomune Group.

Time frame: During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0

Number of Subjects Reporting Serious Adverse Events (SAEs)

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject . This Outcome Measure only concerns subjects in the Menomune Group.

Time frame: During the 31-day follow-up period after vaccination with Menomune vaccine at Day 0

Number of Subjects With Anti-PRP Antibody Concentrations ≥ the Cut-off Values

Anti-PRP antibody cut-off values for this outcome were 0.15 µg/mL and 1.0 µg/mL. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Anti-PRP Antibody Concentrations

Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations ≥ Cut-off

The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.05 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations ≥ Cut-off

The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.2 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations ≥ Cut-off

The Streptococcus pneumoniae antibody cut-off value for this outcome was 0.5 µg/mL for the 7 serotypes in Prevnar vaccine. Prevnar vaccine pneumococcal serotypes included the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Number of Subjects With Anti-diphtheria and Anti-tetanus Antibody Concentration ≥ 0.1 International Units Per Milliliter (IU/mL)

The anti-diphtheria and anti-tetanus antibody cut-off value for this outcome was ≥ 0.1 IU/mL. This Outcome Measure only concerns the MenHibrix and ActHIB groups.

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Anti-diphtheria and Anti-tetanus Antibody Concentrations

Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as international units per milliliter (IU/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Number of Subjects With Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentration ≥ 10.0 Milli-international Units Per Milliliter (mIU/mL)

This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Anti-hepatitis-B Surface Antigen (Anti-HBs) Antibody Concentrations

Concentrations of antibodies are presented as geometric mean concentrations (GMCs) expressed as milli-international units per milliliter (mIU/mL). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration ≥ 5.0 EL.U/mL

This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Anti PT, Anti-FHA and Anti-PRN Antibody Concentrations

Concentrations of antibodies are presented as GMCs expressed as EL.U/mL. Results for one month after the 3-dose primary vaccination course (at Month 5) are presented under the Primary Outcome Measures section. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to the primary vaccination course (at Day 0)

Number of Subjects With Anti-poliovirus Types 1, 2 and 3 Antibody Titer ≥ 1:8

This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Anti-poliovirus Types 1, 2 and 3 Antibody Titers

Titers are presented as geometric mean titers (GMTs). This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Prior to and one month after the primary vaccination course (at Day 0 and Month 5)

Number of Subjects With Vaccine Response to PT, FHA and PRN

Vaccine response to PT/FHA/PRN was defined as, for initially seronegative subjects, antibody concentration ≥ 5 EL.U/mL one month post-primary vaccination course, and, for initially seropositive subjects, antibody concentration one month post-primary vaccination course ≥ 1-fold the pre-vaccination antibody concentration. A seronegative/seronegative subject was defined as a subject with antibody concentration \</≥ 5 EL.U/mL for anti-PT/FHA/PRN prior to vaccination. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: One month after the 3-dose primary vaccination course (at Month 5)

Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited Local Symptoms

Solicited local symptoms were pain, redness and swelling at injection site. "Any" = any report of the specified symptom irrespective of intensity grade; "Grade 2 pain" = cried/protested on touch; "Grade 3 pain" = cried when limb was moved/spontaneously painful; "Grade 2 or 3" redness/swelling = redness/swelling larger than (\>) 10 millimeters (mm); "Grade 3" redness/swelling = redness/swelling \> 30 mm. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Within 4 days (Day 0-3) after the 3-dose primary vaccination

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

Number of Subjects Reporting Any, Grade 2 or 3 and Grade 3 Solicited General Symptoms

Solicited general symptoms were fever, irritability/fussiness, drowsiness, and loss of appetite. "Any" = any report of the specified symptom irrespective of intensity grade and relationship to vaccination. "Grade 2" for Drowsiness, Irritability/Fussiness and Loss of appetite = symptom that interfered with normal activity; "Grade 3" for Drowsiness and Irritability/Fussiness = symptom that prevented normal activity; "Grade 3" Loss of appetite = not eating at all. Fever = rectal temperature ≥ 38.0 degrees Celsius (°C); "Grade 2 or 3" fever = rectal temperature higher than (\>) 39°C; "Grade 3" fever = rectal temperature \> 40°C. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: Within 4 days (Day 0-3) after the 3-dose primary vaccination

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

Number of Subjects Reporting Unsolicited Adverse Events (AEs)

An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms.

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).

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).

Number of Subjects Reporting Serious Adverse Events (SAEs)

SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.

Number of Subjects Reporting New Onset of Chronic Illness(es) (NOCIs)

NOCIs include autoimmune disorders, asthma, type I diabetes, allergies. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine

Number of Subjects Reporting Rash

An episode of rash was defined as an episode of hives, idiopathic thrombocytopenic purpura, petechiae. This Outcome Measure only concerns the MenHibrix and ActHIB groups .

Time frame: From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.

Number of Subjects Reporting Emergency Room (ER) Visits or Visits to Physicians' Office, Related or Not to Common Illnesses

Emergency room (ER) visits or physicians office visits assessed were those unrelated to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infections, otitis media, pharyngitis, gastroenteritis. This Outcome Measure only concerns the MenHibrix and ActHIB groups.

Time frame: From Day 0 following Dose 1 throughout the study up to the day preceding the administration of the fourth dose of vaccine.

Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC and Y)

Fourth dose responses to rSBA-MenC and rSBA-MenY were defined as follows (Definition 1): * Initially seronegative subjects (pre-fourth dose antibody titer below cut-off: \< 1:8) should have an antibody titer at least four-fold higher than the cut-off, one month after fourth dose (post-fourth dose antibody titer ≥1:32), * Initially seropositive subjects (pre-fourth dose antibody titer above cut-off: ≥1:8) should have an antibody titer at least four-fold higher than the pre-fourth dose antibody titer, one month after fourth dose.

Time frame: One month post fourth dose vaccination (at Month 11-14)

Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Rabbit Complement (rSBA-MenC and Y)

Fourth dose responses to rSBA-MenC and rSBA-MenY were also assessed using a second definition (Definition 2): * Post-fourth dose rSBA antibody titers ≥1:32 in subjects seronegative at the pre-fourth dose time point (rSBA antibody titers \< 1:8), * At least (i.e., greater than or equal to) a 4-fold rise in rSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:8 but \< 1:128, * At least (i.e., greater than or equal to) a 2-fold rise in rSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:128.

Time frame: One month post fourth dose vaccination (at Month 11-14)

Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Human Complement (hSBA-MenC and Y)

Fourth dose responses to hSBA-MenC and hSBA-MenY were defined as follows (Definition 1): * Initially seronegative subjects (pre-fourth dose antibody titer below cut-off: \< 1:8) should have an antibody titer at least four-fold higher than the cut-off, one month after the fourth dose (post-fourth dose antibody titer ≥1:16), * Initially seropositive subjects (pre-fourth dose antibody titer above cut-off: ≥1:8) should have an antibody titer at least four-fold higher than the pre-fourth dose antibody titer, one month after the fourth dose.

Time frame: One month post fourth dose vaccination (at Month 11-14)

Number of Subjects With Fourth Dose Response for Neisseria Meningitidis Serogroup C and Y Serum Bacterial Assay Using Human Complement (hSBA-MenC and Y)

Fourth dose responses to hSBA-MenC and hSBA-MenY were also assessed using a second definition (Definition 2): * Post-fourth dose hSBA antibody titers ≥1:16 in subjects seronegative at the pre-fourth dose time point (hSBA antibody titers \< 1:8), * At least (i.e., greater than or equal to) a 4-fold rise in hSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:4 but \< 1: 8, * At least (i.e., greater than or equal to) a 2-fold rise in hSBA antibody titers in subjects with pre-fourth dose antibody titers ≥1:8.

Time frame: One month post fourth dose vaccination (at Month 11-14)

Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.05 Microgram Per Milliliter (µg/mL)

Streptococcus pneumoniae antibody cut-off values assessed was ≥0.05 µg/mL for the 7 serotypes in Prevnar vaccine. Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.

Time frame: One month after fourth dose vaccination (at Month 11-14)

Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.2 Microgram Per Milliliter (µg/mL)

Streptococcus pneumoniae antibody cut-off values assessed was ≥0.2 µg/mL for the 7 serotypes in Prevnar vaccine. Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.

Time frame: One month after fourth dose vaccination (at Month 11-14)

Number of Subjects With Streptococcus Pneumoniae Serotypes Antibody Concentrations Equal to or Above 0.5 Microgram Per Milliliter (µg/mL)

Streptococcus pneumoniae antibody cut-off values assessed was ≥0.5 µg/mL for the 7 serotypes in Prevnar vaccine. Vaccine pneumococcal serotypes included serotypes 4, 6B, 9V, 14, 18C, 19F, 23F.

Time frame: One month after fourth dose vaccination (at Month 11-14)

Concentration of Antibodies Against Streptococcus Pneumonia Serotypes

Time frame: One month post fourth dose vaccination (at Month 11-14)

Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations Equal to or Above the Cut-off Values

Anti-PRP antibody cut-off values assessed were ≥0.15 µg/mL and ≥1.0 µg/mL.