Acellular Pertussis, Tetanus, Poliomyelitis, Diphtheria, Diphtheria-Tetanus-aPertussis-Hepatitis B-Poliomyelitis-Haemophilus Influenzae Type b Vaccines
Conditions
Brief summary
The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' Infanrix hexa, given in the primary vaccination schedule to infants born to pregnant women who participated in study 116945 \[DTPA (BOOSTRIX)-047\]. This study will help us evaluate if the presence of transplacentally transferred maternal antibodies interfere with the immune response to primary vaccination with Infanrix hexa and a co-administered pneumococcal conjugate vaccine given as a part of this study in infants.
Interventions
BIOLOGICALInfanrix hexa
• All subjects will receive Infanrix hexa at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. Infanrix hexa is administered intramuscularly to the right thigh.
DRUGPrevnar13
• All subjects will receive Infanrix hexa co-administered with Prevenar13\* at 2 and 4, at 3 and 5, at 2, 4 and 6 months or at 2, 3 and 4 months, depending on the immunisation schedule of the country. \*In some countries/regions with an Infanrix hexa 3-dose vaccination schedule, Prevenar 13 could be administered as 2-doses or 3-doses primary vaccination schedule (according to the routine national immunisation schedule). Prevnar13 is administered intramuscularly to the left thigh.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 14 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Subjects' parent(s)/Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). * Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. * A male or female between, 6 and 14 weeks of age (including 6 weeks and up to and including 14 weeks and 6 days of age) at the time of the first vaccination. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Born to a mother enrolled in study 116945 \[DTPA (BOOSTRIX)-047\]. * Medically stable\* prematurely born infants, born after a gestation period of 27-36 weeks may be enrolled in the study at the discretion of the investigator. * Medically stable refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study vaccine.
Exclusion criteria
* Child in care * Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting at birth prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥0.5mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. * Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). * Administration of any chronic drug therapy to be continued during the study period. * A vaccine not foreseen by the study protocol administered during the period starting from 30 days before each dose of vaccine and ending 30 days after\*, with the exception of inactivated influenza vaccine and other vaccines given as a part of the national/regional immunisation schedule, that are allowed at any time during the study period. * In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is organised by the public health authorities, outside the routine immunisation program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its SPC or package insert (PI) and according to the local governmental recommendations and provided a written approval of the Sponsor is obtained. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device). * Previous vaccination against Hib, diphtheria, tetanus, pertussis, pneumococcus, and/or poliovirus since birth. * History of Hib, diphtheria, tetanus, pertussis, pneumococcal, poliovirus and hepatitis B diseases. * Any confirmed or suspected immunosuppressive or immunodeficient condition including severe combined immunodeficiency disease (SCID), based on medical history and physical examination (no laboratory testing required). * Family history of congenital or hereditary immunodeficiency. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. * Major congenital defects * Serious chronic illness. * History of any neurological disorders or seizures. * Acute disease and/or fever at the time of enrolment. * Fever is defined as temperature ≥37.5°C/99.5°F for oral, axillary or tympanic route, or ≥38.0°C/100.4°F for rectal route. * Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator. * Administration of immunoglobulins and/or any blood products during the period starting at birth before the first dose of study vaccines or planned administration during the study period. * Hypersensitivity to latex.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | 1 month after the last dose of the primary vaccination | Vaccine response to the PT, FHA and PRN antigens, is defined as the appearance of antibodies in subjects who were initially seronegative (i.e., with concentrations lower than (\<) the cut-off value of the assay), or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., with concentrations greater than or equal to (≥) the cut-off value of the assay). Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, 2.187 IU/mL for anti-PRN. |
| Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off | 1 month after the last dose of the primary vaccination | A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.1 International Units per milliliter (IU/mL). |
| Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off | 1 month after the last dose of the primary vaccination | A seroprotected subject is a subject whose antibody concentration/titre was ≥ to the level defining clinical protection, of 10 micro International Units per milliliter (mIU/mL). |
| Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | 1 month after the last dose of the primary vaccination | A seroprotected subject is a subject whose antibody titre was ≥ the level defining clinical protection, of 8 ED50. |
| Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off | 1 month after the last dose of the primary vaccination | A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.15 micrograms per milliliter (µg/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-HBs Antibody Concentrations | 1 month after the last dose of the primary vaccination | Anti-HBs antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in mIU/mL. |
| Anti-PRP Antibody Concentrations | 1 month after the last dose of the primary vaccination | Anti-PRP antibody concentrations were expressed as GMCs and measured in µg/mL. |
| Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | 1 month after the last dose of the primary vaccination | Anti-PT, anti-FHA, anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL. |
| Anti-pneumococcal Antibody Concentrations | 1 month after the last dose of the primary vaccination | Assessed anti-pneumococcal serotypes were (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), expressed as GMCs and measured in µg/mL. |
| Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off. | Before the first dose of Infanrix hexa | A seroprotected subject is a subject whose antibody concentration was ≥ the level defining clinical protection, of 0.1 IU/mL. |
| Number of Subjects With Solicited Local Symptoms | During the 4-day (Day 0-Day 3) follow-up period after each vaccination | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Solicited local symptoms were assessed by each and across dose. |
| Number of Subjects With Solicited General Symptoms | During the 4-day (Day 0-Day 3) follow-up period after each vaccination | Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite and fever \[defined as axillary route temperature ≥ 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade. Solicited general symptoms were assessed by each and across dose. |
| Number of Subjects With Unsolicited Adverse Events | During the 31-day (days 0-30) follow-up period after each vaccination | 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 is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. |
| Number of Subjects With Serious Adverse Events (SAEs) | From Day 0, prior to vaccination until the study end, at Month 3 or 5 (depending on vaccination schedule of the country) | SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. |
| Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | 1 month after the last dose of the primary vaccination | A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN |
| Anti-D and Anti-T Antibody Concentrations | Before the first dose of Infanrix hexa | Antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in IU/mL. |
| Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | Before the first dose of Infanrix hexa | A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN |
| Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | Before the first dose of Infanrix hexa | Anti-PT, anti-FHA and anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL. |
| Anti-Polio Type 1, 2 and 3 Antibody Titers | 1 month after the last dose of the primary vaccination | Anti-Polio type 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMT). |
Countries
Australia, Canada, Czechia, Finland, Italy, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| dTpa Group Infants born to mothers belonging to the Boostrix Group in study NCT02377349 \[DTPA (BOOSTRIX)-047\] i.e. who received a single dose of Boostrix during pregnancy and a dose of placebo immediately post-delivery. All infants in this group received Infanrix hexa co-administered with Prevenar 13 according to the routine national immunisation schedule. | 296 |
| Control Group Infants born to mothers belonging to the Control group in study NCT02377349 \[DTPA (BOOSTRIX)-047\], i.e. who received a single dose of placebo during pregnancy and a dose of Boostrix immediately post-delivery. All infants in this group received Infanrix hexa co-administered with Prevenar 13 according to the routine national immunisation schedule. | 305 |
| Total | 601 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Migrated/moved from study area | 3 | 1 |
| Overall Study | Serious Adverse Event | 1 | 0 |
| Overall Study | Subject vaccinated outside of the study | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Control Group | Total | dTpa Group |
|---|---|---|---|
| Age, Continuous | 8.9 Weeks STANDARD_DEVIATION 1.8 | 8.8 Weeks STANDARD_DEVIATION 1.7 | 8.7 Weeks STANDARD_DEVIATION 1.6 |
| Race/Ethnicity, Customized African Heritage / African American | 9 Participants | 13 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Mixed origin | 8 Participants | 26 Participants | 18 Participants |
| Race/Ethnicity, Customized White - Arabic / North African Heritage | 3 Participants | 4 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Caucasian / European Heritage | 285 Participants | 553 Participants | 268 Participants |
| Sex: Female, Male Female | 144 Participants | 285 Participants | 141 Participants |
| Sex: Female, Male Male | 161 Participants | 316 Participants | 155 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 296 | 0 / 305 |
| other Total, other adverse events | 292 / 296 | 294 / 305 |
| serious Total, serious adverse events | 7 / 296 | 17 / 305 |
Outcome results
Primary
Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off
A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.1 International Units per milliliter (IU/mL).
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off | anti-D antibody | 264 Participants |
| dTpa Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off | anti-T antibody | 266 Participants |
| Control Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off | anti-D antibody | 271 Participants |
| Control Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off | anti-T antibody | 271 Participants |
Primary
Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off
A seroprotected subject is a subject whose antibody concentration/titre was ≥ to the level defining clinical protection, of 10 micro International Units per milliliter (mIU/mL).
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| dTpa Group | Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off | 251 Participants |
| Control Group | Number of Seroprotected Subjects With Anti Hepatitis B (Anti-HBs) Antibody Concentration Above or Equal to the Assay Cut-off | 259 Participants |
Primary
Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8
A seroprotected subject is a subject whose antibody titre was ≥ the level defining clinical protection, of 8 ED50.
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | anti-Polio 1 antibody | 233 Participants |
| dTpa Group | Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | anti-Polio 2 antibody | 239 Participants |
| dTpa Group | Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | anti-Polio 3 antibody | 228 Participants |
| Control Group | Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | anti-Polio 1 antibody | 242 Participants |
| Control Group | Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | anti-Polio 2 antibody | 235 Participants |
| Control Group | Number of Seroprotected Subjects With Anti-poliovirus Type 1, 2 and 3 Antibody Concentration Above or Equal to 8 | anti-Polio 3 antibody | 236 Participants |
Primary
Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off
A seroprotected subject is a subject whose antibody concentration/titre was ≥ the level defining clinical protection, of 0.15 micrograms per milliliter (µg/mL).
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| dTpa Group | Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off | 255 Participants |
| Control Group | Number of Seroprotected Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Above or Equal to the Assay Cut-off | 256 Participants |
Primary
Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens
Vaccine response to the PT, FHA and PRN antigens, is defined as the appearance of antibodies in subjects who were initially seronegative (i.e., with concentrations lower than (\<) the cut-off value of the assay), or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (i.e., with concentrations greater than or equal to (≥) the cut-off value of the assay). Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA, 2.187 IU/mL for anti-PRN.
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the Totally vaccinated cohort (TVC) who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | anti-PT antibody | 185 Participants |
| dTpa Group | Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | anti-FHA antibody | 95 Participants |
| dTpa Group | Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | anti-PRN antibody | 90 Participants |
| Control Group | Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | anti-PT antibody | 249 Participants |
| Control Group | Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | anti-FHA antibody | 238 Participants |
| Control Group | Number of Subjects With Vaccine Response Against Pertussis Toxoid (PT), Filamentous Haemagglutinin (FHA) and Pertactin (PRN) Antigens | anti-PRN antibody | 225 Participants |
Secondary
Anti-D and Anti-T Antibody Concentrations
Antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in IU/mL.
Time frame: Before the first dose of Infanrix hexa
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| dTpa Group | Anti-D and Anti-T Antibody Concentrations | anti-D antibody | 0.423 IU/mL |
| dTpa Group | Anti-D and Anti-T Antibody Concentrations | anti-T antibody | 2.152 IU/mL |
| Control Group | Anti-D and Anti-T Antibody Concentrations | anti-D antibody | 0.089 IU/mL |
| Control Group | Anti-D and Anti-T Antibody Concentrations | anti-T antibody | 0.378 IU/mL |
Secondary
Anti-D and Anti-T Antibody Concentrations
Antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in IU/mL.
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| dTpa Group | Anti-D and Anti-T Antibody Concentrations | anti-D antibody | 1.747 IU/ml |
| dTpa Group | Anti-D and Anti-T Antibody Concentrations | anti-T antibody | 2.347 IU/ml |
| Control Group | Anti-D and Anti-T Antibody Concentrations | anti-T antibody | 2.278 IU/ml |
| Control Group | Anti-D and Anti-T Antibody Concentrations | anti-D antibody | 2.746 IU/ml |
Secondary
Anti-HBs Antibody Concentrations
Anti-HBs antibody concentrations were expressed as geometric mean concentrations (GMCs) and measured in mIU/mL.
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| dTpa Group | Anti-HBs Antibody Concentrations | 1322.8 mIU/ml |
| Control Group | Anti-HBs Antibody Concentrations | 1339.2 mIU/ml |
Secondary
Anti-pneumococcal Antibody Concentrations
Assessed anti-pneumococcal serotypes were (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), expressed as GMCs and measured in µg/mL.
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 4 antibody | 1.20 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 9V antibody | 1.33 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 6A antibody | 2.16 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 14 antibody | 5.70 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 3 antibody | 0.54 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 18C antibody | 1.61 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 6B antibody | 1.37 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 19A antibody | 1.61 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 5 antibody | 1.09 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 19F antibody | 2.57 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 7F antibody | 2.39 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 23F antibody | 0.86 µg/mL |
| dTpa Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 1 antibody | 1.61 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 23F antibody | 1.02 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 1 antibody | 1.92 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 3 antibody | 0.60 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 4 antibody | 1.56 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 5 antibody | 1.27 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 6A antibody | 2.59 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 6B antibody | 1.44 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 7F antibody | 2.67 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 9V antibody | 1.64 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 14 antibody | 6.57 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 18C antibody | 1.79 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 19A antibody | 2.01 µg/mL |
| Control Group | Anti-pneumococcal Antibody Concentrations | anti-PnPS 19F antibody | 3.24 µg/mL |
Secondary
Anti-Polio Type 1, 2 and 3 Antibody Titers
Anti-Polio type 1, 2 and 3 antibody titers were expressed as geometric mean titers (GMT).
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| dTpa Group | Anti-Polio Type 1, 2 and 3 Antibody Titers | anti-Polio 3 antibody | 730.6 Titers |
| dTpa Group | Anti-Polio Type 1, 2 and 3 Antibody Titers | anti-Polio 1 antibody | 432.1 Titers |
| dTpa Group | Anti-Polio Type 1, 2 and 3 Antibody Titers | anti-Polio 2 antibody | 424.6 Titers |
| Control Group | Anti-Polio Type 1, 2 and 3 Antibody Titers | anti-Polio 2 antibody | 388.4 Titers |
| Control Group | Anti-Polio Type 1, 2 and 3 Antibody Titers | anti-Polio 3 antibody | 775.6 Titers |
| Control Group | Anti-Polio Type 1, 2 and 3 Antibody Titers | anti-Polio 1 antibody | 489.9 Titers |
Secondary
Anti-PRP Antibody Concentrations
Anti-PRP antibody concentrations were expressed as GMCs and measured in µg/mL.
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| dTpa Group | Anti-PRP Antibody Concentrations | 1.862 µg/mL |
| Control Group | Anti-PRP Antibody Concentrations | 1.717 µg/mL |
Secondary
Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations
Anti-PT, anti-FHA and anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL.
Time frame: Before the first dose of Infanrix hexa
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| dTpa Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | anti-PT antibody | 11.9 IU/ml |
| dTpa Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | anti-FHA antibody | 88.3 IU/ml |
| dTpa Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | anti-PRN antibody | 70.5 IU/ml |
| Control Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | anti-PT antibody | 2.2 IU/ml |
| Control Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | anti-FHA antibody | 6.6 IU/ml |
| Control Group | Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations | anti-PRN antibody | 4.5 IU/ml |
Secondary
Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations
Anti-PT, anti-FHA, anti-PRN antibody concentrations were expressed as GMCs and measured in IU/mL.
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| dTpa Group | Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | anti-PT antibody | 32.7 IU/mL |
| dTpa Group | Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | anti-FHA antibody | 68.5 IU/mL |
| dTpa Group | Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | anti-PRN antibody | 60.5 IU/mL |
| Control Group | Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | anti-PT antibody | 54.7 IU/mL |
| Control Group | Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | anti-FHA antibody | 103.5 IU/mL |
| Control Group | Anti-PT, Anti-FHA, Anti-PRN Antibody Concentrations | anti-PRN antibody | 92.0 IU/mL |
Secondary
Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off.
A seroprotected subject is a subject whose antibody concentration was ≥ the level defining clinical protection, of 0.1 IU/mL.
Time frame: Before the first dose of Infanrix hexa
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off. | anti-D antibody | 200 Participants |
| dTpa Group | Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off. | anti-T antibody | 240 Participants |
| Control Group | Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off. | anti-D antibody | 110 Participants |
| Control Group | Number of Seroprotected Subjects Against Diphtheria (Anti-D) and Tetanus (Anti-T) Antibody Concentration Above or Equal to the Assay Cut-off. | anti-T antibody | 225 Participants |
Secondary
Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off.
A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN
Time frame: Before the first dose of Infanrix hexa
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PT antibody | 218 Participants |
| dTpa Group | Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-FHA antibody | 242 Participants |
| dTpa Group | Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PRN antibody | 231 Participants |
| Control Group | Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PT antibody | 88 Participants |
| Control Group | Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-FHA antibody | 210 Participants |
| Control Group | Number of Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PRN antibody | 151 Participants |
Secondary
Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off.
A seropositive subject is a subject whose antibody concentration is ≥ the assay cut-off defined. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA,2.187 IU/mL for anti-PRN
Time frame: 1 month after the last dose of the primary vaccination
Population: The analysis was performed on the According to Protocol (ATP) cohort for immunogenicity, which included all subjects from the TVC who complied with the vaccine administration and with the protocol and for whom data concerning immunogenicity outcome measures were available for at least one study vaccines antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PT antibody | 266 Participants |
| dTpa Group | Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-FHA antibody | 266 Participants |
| dTpa Group | Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PRN antibody | 266 Participants |
| Control Group | Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PT antibody | 271 Participants |
| Control Group | Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-FHA antibody | 271 Participants |
| Control Group | Number of Subjects With Anti-PT, Anti-FHA, Anti-PRN Antibody Concentration Above or Equal to the Assay Cut-off. | anti-PRN antibody | 269 Participants |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
SAEs assessed included medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.
Time frame: From Day 0, prior to vaccination until the study end, at Month 3 or 5 (depending on vaccination schedule of the country)
Population: The analysis was performed on the Total vaccinated cohort (TVC), which included all vaccinated subjects for whom data were available and for those with at least 1 vaccine administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| dTpa Group | Number of Subjects With Serious Adverse Events (SAEs) | 7 Participants |
| Control Group | Number of Subjects With Serious Adverse Events (SAEs) | 17 Participants |
Secondary
Number of Subjects With Solicited General Symptoms
Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite and fever \[defined as axillary route temperature ≥ 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade. Solicited general symptoms were assessed by each and across dose.
Time frame: During the 4-day (Day 0-Day 3) follow-up period after each vaccination
Population: The analysis was performed on the Total vaccinated cohort (TVC), which included all vaccinated subjects for whom data were available and for those with at least 1 vaccine administration documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Dose 1 | 166 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Irritability / Fussiness, Dose 1 | 187 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Loss of Appetite, Dose 1 | 85 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Dose 1 | 64 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Dose 2 | 142 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Irritability / Fussiness, Dose 2 | 182 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Loss of Appetite, Dose 2 | 69 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Dose 2 | 62 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Dose 3 | 99 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Irritability / Fussiness, Dose 3 | 142 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Loss of Appetite, Dose 3 | 64 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Dose 3 | 52 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Across Doses | 216 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Irritability/Fussiness, Across Doses | 255 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Loss of appetite, Across Doses | 142 Participants |
| dTpa Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Across Doses | 125 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Across Doses | 126 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Dose 1 | 174 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Dose 3 | 104 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Irritability / Fussiness, Dose 1 | 191 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Across Doses | 232 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Loss of Appetite, Dose 1 | 94 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Irritability / Fussiness, Dose 3 | 161 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Dose 1 | 69 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Loss of appetite, Across Doses | 157 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Drowsiness, Dose 2 | 149 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Loss of Appetite, Dose 3 | 63 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Irritability / Fussiness, Dose 2 | 194 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Irritability/Fussiness, Across Doses | 257 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Loss of Appetite, Dose 2 | 94 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Dose 3 | 47 Participants |
| Control Group | Number of Subjects With Solicited General Symptoms | Any Temperature/(Axillary) (≥37.5°C), Dose 2 | 76 Participants |
Secondary
Number of Subjects With Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Solicited local symptoms were assessed by each and across dose.
Time frame: During the 4-day (Day 0-Day 3) follow-up period after each vaccination
Population: The analysis was performed on the Total vaccinated cohort (TVC), which included all vaccinated subjects for whom data were available and for those with at least 1 vaccine administration documented.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Dose 1 | 120 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Dose 1 | 128 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Dose 1 | 81 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Dose 2 | 109 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Dose 2 | 139 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Dose 2 | 98 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Dose 3 | 85 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Dose 3 | 122 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Dose 3 | 77 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Across Doses | 175 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Across Doses | 205 Participants |
| dTpa Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Across Doses | 157 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Across Doses | 203 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Dose 1 | 120 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Dose 3 | 94 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Dose 1 | 116 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Across Doses | 184 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Dose 1 | 87 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Dose 3 | 134 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Pain, Dose 2 | 101 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Across Doses | 168 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Redness, Dose 2 | 139 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Dose 3 | 109 Participants |
| Control Group | Number of Subjects With Solicited Local Symptoms | Any Swelling, Dose 2 | 95 Participants |
Secondary
Number of Subjects With Unsolicited Adverse Events
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 is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time frame: During the 31-day (days 0-30) follow-up period after each vaccination
Population: The analysis was performed on the Total vaccinated cohort (TVC), which included all vaccinated subjects for whom data were available and for those with at least 1 vaccine administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| dTpa Group | Number of Subjects With Unsolicited Adverse Events | 161 Participants |
| Control Group | Number of Subjects With Unsolicited Adverse Events | 173 Participants |