Consistency & Immunogenicity Study of 3 Lots of GSK's Hib Conjugate Vaccine Versus ActHIB & Pentacel in Healthy Infants

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).

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.

Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).

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.

Antibody concentrations against S.pneumoniae were given as geometric mean concentrations (GMCs) expressed as microgram per milliliter (µg/mL).

Seroresponse (95%) was defined as the number of subjects showing a concentration above a threshold that leads to 95% seroresponse in the ActHIB group.

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.

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

Antibody concentrations were given as geometric mean concentrations (GMCs) and expressed as International Units per milliliter (IU/mL).

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.

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).

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.

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.

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.

Seroresponse (90%) was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.

Seroresponse was defined as the number of subjects showing a concentration above a threshold that leads to 90% seroresponse in the ActHIB group.

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.

Antibody concentrations were tabulated as geometric mean concentrations (GMCs) and expressedas milli-international units per milliliter (mIU/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.

Antibody titers were given as geometric mean titers(GMTs).

The cut-off values were defined as a concentration≥ 3.3 mIU/mL (seropositivity) and ≥ 10 mIU/mL (seroprotection).

Antibody concentrations were given as Geometric Mean Concentrations (GMCs) expressed in micrograms per milliliter (µg/mL).

Antibody concentrations were expressed as geometric mean concentrations (GMCs) and expressed as milli-international units per milliliter (mIU/mL).

The cut-off values were defined as a concentration≥ 6.2 mIU/mL (seropositivity) and ≥ 10 mIU/mL (seroprotection).

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.

Antibody concentrations were tabulated as geometric mean titers (GMTs) and expressed as titers.

Anti-polio 1,2,3 antibody titers greater or equal to the cut off value were calculated.

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.

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any symptom regardless of intensity grade.

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).

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.

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.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

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.