This study is evaluating the safety and immunogenicity of Hib-MenCY-TT vaccine compared to control groups receiving licensed Hib or MenC conjugate vaccines, each administered at 2, 4, 6, and 12 to 15 months of age. Co-administration with live, attenuated measles, mumps, and rubella combination vaccine; and with live, attenuated varicella vaccine will be assessed with administration of the booster dose. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, September 2007.
The study will be conducted in 2 stages: a 3-dose primary vaccination at 2, 4 and 6 months of age and a booster vaccination at 12 to 15 months of age. All subjects will have 3 blood samples taken. Half of the subjects of each group will have a blood sample taken just prior to the administration of the third dose of the primary vaccination and the other half of the subjects of each group will have a blood sample taken at one month after the third vaccine dose of the primary vaccination phase. In addition, all subjects of all groups will have a blood sample taken before and 42 days after administration of the booster dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
1,104
One intramuscular dose at 2, 4 and 6 months of age ( group A) and one intramuscular dose at 12 to 15 months of age (groups A and B)
One intramuscular dose at 2, 4 and 6 months of age
One intramuscular dose at 2, 4 and 6 months of age
One intramuscular dose at 2, 4 and 6 months of age
One intramuscular dose at 2, 4 and 6 months of age
One subcutaneous dose at 12-15 months of age
One subcutaneous dose at 12 to 15 months of age
One intramuscular dose at 12 to 15 months of age
GSK Investigational Site
North Adelaide, South Australia, Australia
GSK Investigational Site
Carlton, Victoria, Australia
GSK Investigational Site
Perth, Western Australia, Australia
Number of Subjects With Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Concentration Greater Than or Equal to 1.0 Microgram Per Milliliter (µg/mL)
The analysis was performed on blood samples taken from half of the subjects in the MenHibrix and ActHIB/PedvaxHib groups only. The other half of the subjects in these study groups donated a blood sample after the second vaccine dose for analysis of the corresponding secondary outcome measure.
Time frame: One month after the 3-dose primary vaccination course
Number of Subjects With Meningococcal Polysaccharide C Serum Bactericidal Activity/Assay Using Baby Rabbit Complement (rSBA-MenC) Titer Greater Than or Equal to 1:128
The analysis was performed on blood samples taken from half of the subjects in the MenHibrix and ActHIB + Meningitec groups only. The other half of the subjects in these study groups donated a blood sample after the second vaccine dose for analysis of the corresponding secondary outcome measure.
Time frame: One month after the 3-dose primary vaccination course
Number of Subjects Seroconverted for Anti-measles Antibodies
The analysis was performed on blood samples taken from the subjects in the MenHibrix and ActHIB groups only. Anti-measles seroconversion is defined as the appearance of antibodies (i.e. concentration greater than or equal to the cut-off value of 150 milli-international units per milliliter (mIU/mL)) in the serum of subjects seronegative (below 150 mIU/mL) before vaccination.
Time frame: 42 days after the fourth dose vaccination
Number of Subjects Seroconverted for Anti-mumps Antibodies
The analysis was performed on blood samples taken from the subjects in the MenHibrix and ActHIB groups only. Anti-mumps seroconversion is defined as titer greater than or equal to 28 ED50 in subjects seronegative (\<28 ED50) before vaccination. ED50 is defined as the reciprocal of the sample dilution in the neutralising assay reducing the number of viral plaques by fifty percent.
Time frame: 42 days after the fourth dose vaccination
Number of Subjects With an Anti-rubella Seroresponse
The analysis was performed on blood samples taken from the subjects in the MenHibrix and ActHIB groups only. Anti-rubella seroresponse is defined as post-vaccination concentration greater than or equal to 10 IU/mL (ELISA, Enzygnost) in subjects seronegative (concentration below 4 IU/mL) before vaccination.
Time frame: 42 days after the fourth dose vaccination
Number of Subjects Seroconverted for Anti-varicella Antibodies
The analysis was performed on blood samples taken from the subjects in the MenHibrix and ActHIB groups only. Anti-varicella seroconversion is defined as post-vaccination titers greater than or equal to 1:5, in subjects seronegative (titers below 1:5) before vaccination.
Time frame: 42 days after the fourth dose vaccination
Number of Subjects With rSBA-MenC Titer Greater Than or Equal to Pre-defined Cut-off Values
The analyses for post-Dose 2 and post-Dose 3 data were performed on blood samples taken from the respective half of the subjects at both time points. The cut-off values assessed were titers 1:8 and 1:128.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
rSBA-MenC Titers
The analyses for post-Dose 2 and post-Dose 3 data were performed on blood samples taken from the respective half of the subjects at both time points. Titers are given as Geometric Mean Titers.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Number of Subjects With rSBA-MenY Titer Greater Than or Equal to Pre-defined Cut-off Values
The analyses for post-Dose 2 and post-Dose 3 data were performed on blood samples taken from the respective half of the subjects at both time points. The cut-off values assessed were titers 1:8 and 1:128.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
rSBA-MenY Titers
The analyses for post-Dose 2 and post-Dose 3 data were performed on blood samples taken from the respective half of the subjects at both time points. Titers are given as Geometric Mean Titers.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Number of Subjects With Meningococcal Polysaccharide C Serum Bactericidal Activity/Assay Using Human Complement (hSBA-MenC) Antibody Titer Greater Than or Equal to Pre-defined Cut-off Values
The analysis for was performed on the first 30% of the blood samples taken at each time point. The cut-off values assessed were titers 1:4 and 1:8.
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Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
hSBA-MenC Titers
The analysis for was performed on the first 30% of the blood samples taken at each time point. Titers are given as Geometric Mean Titers.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Number of Subjects With Meningococcal Polysaccharide Y Serum Bactericidal Activity/Assay Using Human Complement (hSBA-MenY) Antibody Titer Greater Than or Equal to Pre-defined Cut-off Values
The analysis for was performed on the first 30% of the blood samples taken at each time point. The cut-off values assessed were titers 1:4 and 1:8.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
hSBA-MenY Titers
The analysis for was performed on the first 30% of the blood samples taken at each time point. Titers are given as Geometric Mean Titers.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Number of Subjects With Anti-Polysaccharide C (Anti-PSC) Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
The analysis for post-Dose 2 and post-Dose 3 data was performed on blood samples taken from the respective half of the subjects at both time points. The cut-off values assessed were 0.3 µg/mL and 2 µg/mL.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Anti-PSC Concentrations
The analysis for post-Dose 2 and post-Dose 3 data was performed on blood samples taken from the respective half of the subjects at both time points. Concentrations are given as Geometric Mean Concentrations.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Number of Subjects With Anti-Polysaccharide Y (Anti-PSY) Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
The analysis for post-Dose 2 and post-Dose 3 data was performed on blood samples taken from the respective half of the subjects at both time points. The cut-off values assessed were 0.3 µg/mL and 2 µg/mL.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Anti-PSY Concentrations
The analysis for post-Dose 2 and post-Dose 3 data was performed on blood samples taken from the respective half of the subjects at both time points. Concentrations are given as Geometric Mean Concentrations.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Number of Subjects With Anti-PRP Antibody Concentration Greater Than or Equal to Pre-defined Cut-off Values
The analysis for post-Dose 2 and post-Dose 3 data was performed on blood samples taken from the respective half of the subjects at both time points. The cut-off values assessed were 0.15 µg/mL and 1.0 µg/mL.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Anti-PRP Concentrations
The analysis for post-Dose 2 and post-Dose 3 data was performed on blood samples taken from the respective half of the subjects at both time points. Concentrations are given as Geometric Mean Concentrations.
Time frame: After the second vaccine dose (post-dose 2), one month after the 3-dose primary vaccination course (post-dose 3), just prior to (pre-dose 4) and 42 days after the fourth dose (post-dose 4)
Number of Subjects With Anti-measles Concentration Greater Than or Equal to 150 mIU/mL
The cut-off value assessed was 150 mIU/mL.
Time frame: Just prior to the fourth dose and 42 days after the fourth dose
Number of Subjects With Anti-mumps Titer Greater Than or Equal to 24 ED50
ED50 is defined as the reciprocal of the sample dilution in the neutralising assay reducing the number of viral plaques by fifty percent.
Time frame: Just prior to the fourth dose and 42 days after the fourth dose
Number of Subjects With Anti-rubella Concentration Greater Than or Equal to 4 IU/mL
The cut-off value assessed was 4 IU/mL.
Time frame: Just prior to the fourth dose and 42 days after the fourth dose
Number of Subjects With Anti-varicella Titer Greater Than or Equal to 1:5
The cut-off value assessed was a titer of 1:5.
Time frame: Just prior to the fourth dose and 42 days after the fourth dose
Number of Subjects With a Fourth Dose Response for hSBA-MenC
Fourth dose response for hSBA-MenC is defined as: •For initially seronegative subjects (i.e., subjects with pre fourth dose hSBA antibody titer below 1:4), post fourth dose hSBA antibody titer greater than or equal to 1:16; •For initially seropositive subjects (i.e., subjects with pre fourth dose antibody titer greater than or equal to 1:4), post fourth dose hSBA antibody titer greater than or equal to 1:128.
Time frame: 42 days after the fourth dose
Number of Subjects With a Fourth Dose Response for hSBA-MenY
Fourth dose response for hSBA-MenY defined as: •For initially seronegative subjects (i.e., pre fourth dose hSBA antibody titer \< 1:4), post fourth dose hSBA antibody titer greater than or equal to (≥) 1:16; •For initially seropositive subjects with pre fourth dose hSBA antibody titer ≥ 1:4 and \< 1:64, post fourth dose hSBA antibody titer at least 4-fold higher than the pre fourth dose hSBA antibody titer; •For initially seropositive subjects with pre fourth dose hSBA antibody titer ≥ 1:64, post fourth dose hSBA antibody titer at least 2-fold higher than the pre fourth dose hSBA antibody titer.
Time frame: 42 days after the fourth dose
Number of Subjects With Anti-measles Concentration Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
The pre-defined cut-off values were 150 mIU/mL and 200 mIU/mL. Initially seronegative subjects are defined as subjects with pre-vaccination anti-measles concentration below 150 mIU/mL.
Time frame: 42 days after the fourth dose
Anti-measles Concentrations in Initially Seronegative Subjects
Concentrations are presented as Geometric Mean Concentrations expressed as mIU/mL. Initially seronegative subjects are defined as subjects with pre-vaccination anti-measles concentration below 150 mIU/mL.
Time frame: 42 days after the fourth dose
Number of Subjects With Anti-rubella Concentration Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
The pre-defined cut-off values were 4 IU/mL and 10 IU/mL. Initially seronegative subjects are defined as subjects with pre-vaccination anti-measles concentration below 4 IU/mL.
Time frame: 42 days after the fourth dose
Anti-rubella Concentrations in Initially Seronegative Subjects
Concentrations are presented as Geometric Mean Concentrations expressed as IU/mL. Initially seronegative subjects are defined as subjects with pre-vaccination anti-rubella concentration below 4 IU/mL.
Time frame: 42 days after the fourth dose
Number of Subjects With Anti-mumps Titer Greater Than or Equal to 28 ED50 in Subjects With Anti-mumps Titer Below 28 ED50 Before Vaccination
ED50 is defined as the reciprocal of the sample dilution in the neutralising assay reducing the number of viral plaques by fifty percent.
Time frame: 42 days after the fourth dose
Number of Subjects With Anti-mumps Titer Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
The pre-defined cut-off values were 28 ED50 and 51 ED50. Initially seronegative subjects are defined as subjects with pre-vaccination anti-mumps titer below 24 ED50.
Time frame: 42 days after the fourth dose
Anti-mumps Titers in Initially Seronegative Subjects
Titers are presented as Geometric Mean Titers expressed as ED50, the reciprocal of the sample dilution in the neutralising assay reducing the number of viral plaques by fifty percent. Initially seronegative subjects are defined as subjects with pre-vaccination anti-mumps titer below 24 ED50.
Time frame: 42 days after the fourth dose
Number of Subjects With Anti-varicella Titer Greater Than or Equal to Predefined Cut-off Values in Initially Seronegative Subjects
The pre-defined cut-off values were 1:5 and 1:40. Initially seronegative subjects are defined as subjects with pre-vaccination anti-varicella titer below 1:5.
Time frame: 42 days after the fourth dose
Anti-varicella Titers in Initially Seronegative Subjects
Titers are presented as Geometric Mean Titers. Initially seronegative subjects are defined as subjects with pre-vaccination anti-varicella titer below 1:5.
Time frame: 42 days after the fourth dose
Number of Subjects Reporting Solicited Local and General Symptoms During the Primary Vaccination Phase
Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include drowsiness, fever (rectal temperature greater than or equal to 38 degrees Celcius), irritability and loss of appetite.
Time frame: During a 4-day period (Day 0-3) after any vaccine dose in the primary vaccination phase
Number of Subjects Reporting Solicited Local and General Symptoms During the Fourth Dose Vaccination Phase
Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include drowsiness, fever (rectal temperature greater than or equal to 38 degrees Celcius), irritability and loss of appetite.
Time frame: During a 4-day period (Day 0-3) after the fourth dose vaccination phase
Number of Subjects Reporting Unsolicited Adverse Events
Unsolicited adverse event covers any adverse event 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: During the 31-day (Day 0-30) post-primary and post-fourth dose vaccination period
Number of Subjects Reporting Specific Solicited General AEs Related to Measles, Mumps, Rubella Vaccine and Varicella Vaccine
Specific solicited general symptoms assessed include fever (temperature greater than or equal to 38 degrees Celcius), meningismus/ febrile convulsion, parotid / salivary gland swelling and rash.
Time frame: During a 43-day (Day 0-42) after the fourth dose
Number of Subjects Reporting Serious Adverse Events (SAEs), New Onset of Chronic Illnesses (NOCI), Rash, Emergency Room Visits (ER), Physician Office Visits (PO) During the Primary Vaccination Phase
SAEs: medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. NOCI: e.g. autoimmune disorders, asthma, type I diabetes and allergies. Types of rash: hives, idiopathic thrombocytopenic purpura and petechiae. ER and PO visits assessed were not related to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infection, otitis media, pharyngitis and gastroenteritis.
Time frame: From enrolment through the day preceding the fourth dose
Number of Subjects Reporting Serious Adverse Events (SAEs), New Onset of Chronic Illnesses (NOCI), Rash, Emergency Room Visits (ER), Physician Office Visits (PO) During the Fourth Dose Vaccination Phase
SAEs: medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. NOCI: e.g. autoimmune disorders, asthma, type I diabetes and allergies. Types of rash: hives, idiopathic thrombocytopenic purpura and petechiae. ER and PO visits assessed were not related to well-child care, vaccination, injury or common acute illnesses such as upper respiratory tract infection, otitis media, pharyngitis and gastroenteritis.
Time frame: From the day of administration of the fourth dose until the end of the extended safety follow-up period (last study contact at 18-21 months of age