The purpose of this study is to evaluate safety, to demonstrate lot-to-lot consistency of the vaccine, to address the relevant concomitant vaccine administrations and to provide a comparison between GSK Biologicals' Hib conjugate vaccine and the licensed monovalent Hib vaccine ActHIB as well as the licensed combination product Pentacel in infants at 2, 4, 6 and 15-18 months of age. This study is designed with a primary and a booster phase.
This protocol posting has been updated following protocol amendment 3, dated 12 April 2011. The impacted section is: Eligibility Criteria (Exclusion criteria).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
4,003
Three doses of 3 different manufacturing lots in primary study at 2, 4 and 6 months of age as intramuscular injection and one dose as booster vaccination.
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection and one dose as a booster vaccination
Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations Greater Than or Equal to (≥) 0.15 Microgram Per Milliliter (µg/mL) and ≥ 1.0 µg/mL
Non-inferiority of Hiberix to ActHIB, each co-administered with Pediarix, Prevnar13 and Rotarix following 3 primary doses in terms of immune response to PRP (Anti-PRP≥ 0.15 µ g/ml and ≥1.0 µg/mL).
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Anti-Protein-D (Anti-D) and Anti-Protein-T (Anti-T) Antibody Concentrations ≥ 0.1 International Units Per Milliliter (IU/mL)
Non-inferiority of Pediarix co-administered with Hiberix, Prevnar13 and Rotarix compared to Pediarix co-administered with ActHIB, Prevnar13 and Rotarix following 3 primary vaccine doses in terms of immune response to Diphtheria, Tetanus.
Time frame: At 1 month after last dose of primary vaccination
Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations
Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).
Time frame: At 1 month after last dose of primary vaccination
Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA) Antibody Concentrations
Antibody concentrations were given as geometric mean concentrations (GMCs) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter i.e. EL.U/mL.
Time frame: At 1 month after last dose of primary vaccination
Anti-Streptococcus Pneumoniae (S.Pneumoniae) Antibody Concentrations
Antibody concentrations against S.pneumoniae were given as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Seroresponse (95%) to Anti-pertussis Toxoid (Anti-PT), Anti-pertactin (Anti-PRN) and Anti-filamentous Hemagglutinin (Anti-FHA)
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Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
Three doses in primary epoch at 2, 4 and 6 months of age as intramuscular injection
Two oral doses in primary epoch at 2 and 4 months of age
Two or three doses in primary epoch at 2,( 4) and 6 months of age as intramuscular injection
One dose in the booster epoch at 15-18 months of age as intramuscular injection
GSK Investigational Site
Dothan, Alabama, United States
GSK Investigational Site
Benton, Arkansas, United States
GSK Investigational Site
Fayetteville, Arkansas, United States
GSK Investigational Site
Jonesboro, Arkansas, United States
GSK Investigational Site
Little Rock, Arkansas, United States
GSK Investigational Site
Anaheim, California, United States
GSK Investigational Site
Antioch, California, United States
GSK Investigational Site
Daly City, California, United States
GSK Investigational Site
Fountain Valley, California, United States
GSK Investigational Site
Fremont, California, United States
...and 53 more locations
Seroresponse (95%) was defined as the number of subjects showing a concentration above a threshold that leads to 95% seroresponse in the ActHIB group.
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Anti-Polio 1,2,3 Antibody Titres Greater Than or Equal to Cut-off Value
The cut-off value was defined as a concentration ≥ 8 ED50 (ED50 is the concentration at which the protein exhibits 50% of its maximum activity). The polio testing which started at the Biomnis laboratory was stopped because the polio virus micro-neutralization assays were found to be not in line with the quality standards defined in GSK Biologicals' SOPs. As a result, polio testing was restarted at the GSK laboratory and the results were uploaded into the clinical database.
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations ≥ 1.0 µg/mL
Non-inferiority of a booster dose of Hiberix co-administered with Infanrix in subjects 15-18 months of age who received 3 primary vaccine doses of Hiberix to a booster dose of ActHIB co-administered with Infanrix in subjects of 15-18 months of age who received 3 primary vaccine doses of ActHIB in terms of immune response to PRP
Time frame: At 1 month after booster vaccination
Anti-protein-D (Anti-D) and Anti-protein-T (Anti-T) Antibody Concentrations
Antibody concentrations were given as geometric mean concentrations (GMCs) and expressed as International Units per milliliter (IU/mL).
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Any Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.
Time frame: During a 4-day follow-up period (Days 0-3) following any vaccination
Number of Subjects With Any Solicited General Symptoms
Assessed solicited general symptoms were drowsiness, irritability, fever and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Any fever= Rectal temperature equal to or above (≥) 38 degrees Celsius (°C).
Time frame: During a 4-day follow-up period (Days 0-3) following any vaccination
Number of Subjects With Any Unsolicited Adverse Events (AEs).
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: During the 31-day (Day 0-Day 30) follow-up period after primary vaccination
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time frame: From Day 0 until 6 months following the last primary dose
Number of Subjects With AEs of Specific Interest (AESIs)
An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.
Time frame: From Day 0 until 6 months following the last primary dose or the receipt of the booster vaccination, whichever comes first
Number of Subjects With Seroresponse (90%) to Anti-PT, Anti-PRN and Anti-FHA
Seroresponse (90%) was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Anti-PT, Anti-PRN and Anti-FHA Antibody Concentrations ≥ 5 EL.U/mL
Seroresponse was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Anti-polyribosylribitol Phosphate (Anti-PRP) Antibody Concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL
Evaluation of persistence of anti-PRP antibodies induced by three primary vaccine doses of Hiberix, and ActHIB, each co-administered with Pediarix, Prevnar 13 and Rotarix, or Pentacel co-administered with Engerix-B, Rotarix and Prevnar 13 prior to the booster dose of Hiberix, ActHIB or Pentacel at 15-18 months of age and evaluation of immunogenicity of a booster dose of Hiberix co-administered with Infanrix, ActHIB co-administered with Infanrix and Pentacel in terms of the percentage of subjects with anti-PRP concentrations ≥0.15 µg/mL, ≥1.0 µg/mL and GMCs one month after the booster dose.
Time frame: Prior to the booster vaccination and 1 month after the booster vaccination
Anti-Hepatitis B (Anti-HBs) Antibody Concentrations
Antibody concentrations were tabulated as geometric mean concentrations (GMCs) and expressedas milli-international units per milliliter (mIU/mL).
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With S.Pneumoniae Antibody Concentrations ≥ 0.05 µg/mL, ≥ 0.2 µg/mL and ≥1.0 µg/mL
Evaluation of immunogenicity of a 3-dose primary vaccination course of Prevnar 13 co-administered with Hiberix, Rotarix and Pediarix, of Prevnar 13 co-administered with ActHIB, Rotarix and Pediarix and of Prevnar 13 co-administered with Pentacel, Rotarix and Engerix-B in terms of S.pneumoniae GMCs and antibody concentrations ≥ 0.05µg/mL, ≥ 0.2 µg/mL, ≥ 1.0 µg/mL at one month after the last dose of primary vaccination.
Time frame: At 1 month after the last dose of primary vaccination
Antibody Titers for Poliovirus Types 1, 2 and 3
Antibody titers were given as geometric mean titers(GMTs).
Time frame: At 1 month after last dose of primary vaccination
Number of Subjects With Anti-HBs Antibody Concentrations Greater Than or Equal to Cut-off Values
The cut-off values were defined as a concentration≥ 3.3 mIU/mL (seropositivity) and ≥ 10 mIU/mL (seroprotection).
Time frame: At 1 month after last dose of primary vaccination
Anti-polyribosylribitol Phosphate (PRP) Antibody Concentrations
Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).
Time frame: Prior to the booster vaccination and 1 month after the booster vaccination
Anti-Hepatitis B (Anti-HBs) Antibody Concentrations ≥10.0 mIU/mL and ≥6.2 mIU/mL
Antibody concentrations were expressed as geometric mean concentrations (GMCs) and expressed as milli-international units per milliliter (mIU/mL).
Time frame: Prior to the booster vaccination
Number of Subjects With Anti-HB Antibody Concentrations ≥10.0 mlU/mL and ≥6.2mLU/mL
The cut-off values were defined as a concentration≥ 6.2 mIU/mL (seropositivity) and ≥ 10 mIU/mL (seroprotection).
Time frame: Prior to booster vaccination
Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Concentrations ≥ 5 EL.U/mL
Evaluation of persistence of anti-PT, anti-FHA and anti-PRN antibodies induced by Pediarix or Pentacel and Engerix-B prior to the administration of a booster dose of Hib vaccine at 15-18 months of age and evaluation of immunogenicity of a booster dose of Infanrix co-administered with Hiberix, a booster dose of Infanrix co-administered with ActHIB and a booster dose of Pentacel with respect to anti-PT, anti-FHA and anti- PRN antibodies.
Time frame: Prior to the booster vaccination and 1 month after the booster vaccination
Anti-poliovirus Types 1, 2, and 3 Antibody Titres and Titres ≥ 8
Antibody concentrations were tabulated as geometric mean titers (GMTs) and expressed as titers.
Time frame: Prior to the booster vaccination
Number of Subjects With Anti-Polio-1,2,3 Antibody Titers ≥ 8
Anti-polio 1,2,3 antibody titers greater or equal to the cut off value were calculated.
Time frame: Prior to booster vaccination
Number of Subjects With Anti-D and Anti-T Antibody Concentrations ≥ 0.1 IU/mL and ≥1.0 IU/mL, Respectively.
Evaluation of persistence of anti-D, anti-T antibodies induced by Pediarix or Pentacel and Engerix-B prior to the administration of a booster dose of Hib vaccine at 15-18 months of age and evaluation of immunogenicity of a booster dose of Infanrix co-administered with Hiberix, a booster dose of Infanrix co-administered with ActHIB and a booster dose of Pentacel with respect to anti-D and anti-T antibodies.
Time frame: Prior to the booster vaccination and 1 month after the booster vaccination
Number of Subjects With Any Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.
Time frame: Within 4 days (Days 0-3) following the booster dose
Number of Subjects With Any Solicited General Symptoms
Assessed solicited general symptoms were drowsiness, irritability, fever and loss of appetite. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Any fever= Axillary temperature equal to or above (≥) 38 degrees Celsius (°C).
Time frame: Within 4 days (Days 0-3) following the booster dose
Number of Subjects With AEs of Specific Interest (AESIs)
An AESI was defined as an AE including autoimmune diseases and other mediated inflammatory disorders and assessed by the investigator as specific to the treatment administration.
Time frame: From booster dose until 6 months following receipt of the booster dose
Number of Subjects With Any Unsolicited Adverse Events (AEs).
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: Within 31 days (Day 0 to Day 30) following the booster dose
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time frame: From the booster dose until 6 months following receipt of the booster dose
Anti-FHA, Anti-PRN and Anti-PT Antibody Concentrations
Antibody concentrations were given as geometric mean concentrations (GMCs) expressed as enzyme-linked immuno-sorbent assay (ELISA) units per milliliter i.e. EL.U/mL.
Time frame: pre-booster and one month after booster vaccination