Rotavirus Infection, Rotavirus Vaccines
Conditions
Keywords
Immunogenicity, lyophilized formulation, United States, Reactogenicity, Safety, Porcine circovirus -free, Human rotavirus vaccine, liquid formulation, Healthy infants
Brief summary
The purpose of this study is to assess if there is any immune interference between the Porcine circovirus free (PCV-free) liquid Human rotavirus (HRV) vaccine and routine infant vaccinations currently in use in the US, namely Pediarix®, Hiberix® and Prevenar 13® as compared to the currently licensed lyophilized formulation of the HRV vaccine when co-administered with the same routine vaccinations in healthy infants 6-12 weeks of age
Interventions
BIOLOGICALRotarix
Two doses administered orally according to a 0, 2 month schedule as per the immunization schedule for HRV vaccine administration in the US.
BIOLOGICALPediarix
Three doses administered intramuscularly according to a 0, 2, 4 month schedule.
BIOLOGICALHiberix
Three doses administered intramuscularly according to a 0, 2, 4 month schedule.
BIOLOGICALPrevenar 13
Three doses administered intramuscularly according to a 0, 2, 4 month schedule.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Subjects' parent(s)/\[LAR(s)\] who, in the opinion of the investigator can and will comply with the requirements of the protocol. * A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination. * Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure. * Healthy subjects as established by medical history and clinical examination before entering into the study.
Exclusion criteria
* Child in care. * Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day-29 to Day 1), or planned use during the study period. * Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone (≥0.5 mg/kg/day, or equivalent). Inhaled and topical steroids are allowed. * Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. * Administration of long-acting immune-modifying drugs at any time during the study period. * Planned administration/administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of vaccine administration and ending at Visit 4, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study, if administered at a site which is different from the sites used to administer the co-administered vaccines. * 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. * Uncorrected congenital malformation of the gastrointestinal tract that would predispose for Intussusception (IS). * History of IS. * Very prematurely born infants (born ≤28 weeks of gestation). * Family history of congenital or hereditary immunodeficiency. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Major congenital defects or serious chronic illness. * Previous vaccination against Haemophilus type b (Hib), diphtheria, tetanus, pertussis, pneumococcus, RV and/or poliovirus. * Previous confirmed occurrence of RV GE, Hib, diphtheria, tetanus, pertussis, pneumococcus, hepatitis B and/or polio disease. * Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. * GE within 7 days preceding the study vaccine administration. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * Hypersensitivity to latex. * History of any neurological disorders or seizures. * History of Severe combined immunodeficiency (SCID). * Acute disease and/or fever at the time of enrolment. * Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity, the axilla and the rectum. * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Immunogenicity was assessed using Enzyme Linked Immunosorbent Assay (ELISA) in terms of seroprotection rates against diphtheria toxoid. A seroprotected subject is a subject whose antibody concentration is greater than or equal to (≥) the level defining clinical protection. The following seroprotection thresholds were applicable:anti-D antibody concentrations ≥ 0.1 International Units/milliliter (IU/mL), anti-T antibody concentrations ≥ 0.1 IU/mL. |
| Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Immunogenicity was assessed using ChemiLuminescence ImmunoAssay (CLIA) in terms of seroprotection rates against Hepatitis B. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-HB antibody concentrations ≥ 10 milli International Units/milliliter (mIU/mL). |
| Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Immunogenicity was assessed using virus micro-neutralization test in terms of seroprotection rates against polio virus types 1, 2 and 3. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-polio virus types 1, 2 and 3 types antibody titers ≥ 8 Estimated Dose 50% (ED50). |
| Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Antibody concentrations against PT, FHA and PRN were determined and expressed as Geometric Mean Concentrations (GMCs).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. |
| Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Antibody concentrations against pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) were determined and expressed as GMCs in micrograms per milliliter (µg/mL).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. |
| Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 0.15 µg/mL. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 0.15 µg/mL. |
| Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 1.0 µg/mL. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 1.0 µg/mL. |
| Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Seroresponse is defined as the percentage of subjects showing an antibody concentration above a threshold that leads to 95% seroresponse in the HRV lyophilized Group. The cut-offs used were as follows: anti-PT (18.566 IU/mL), anti-FHA (35.711 IU/mL) and anti-PRN (11.034 IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any Solicited General Adverse Events (AEs). | During the 8-day (Days 1-8) follow-up period after each HRV vaccination. | Assessed solicited general AEs were cough/runny nose; diarrhoea; fever measured by 3 routes which were oral, axillary and rectal, defined as temperature ≥ 38.0 degrees Celsius (°C); irritability; loss of appetite and vomiting. Any = any solicited general AE irrespective of its intensity grade and relationship to vaccination |
| Number of Seropositive Subjects With Anti-Rota Virus Immunoglobulin A (Anti-RV IgA) Antibody Concentrations Above or Equal to Cut-off Value of 20 Units/Milliliter (U/mL). | At Month 5 (Three months after Dose 2 of HRV vaccine) | Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 20 U/mL. |
| Number of Subjects With Any Serious Adverse Events (SAEs). | During the entire study period (Day 1 to Month 10) | SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity. |
| Number of Subjects With Any Unsolicited AEs. | During the 31-day (Days 1-31) follow-up period after each HRV vaccination. | Unsolicited AEs assessed include any AE reported in addition to those solicited during the clinical study. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms were reported as an unsolicited AE. Any= Any unsolicited AE irrespective of its intensity grade and relationship to vaccination. |
| Number of Seropositive Subjects With Anti-RV IgA Antibody Concentrations Above or Equal to Cut-off Value of 90 U/mL. | At Month 5 (Three months after Dose 2 of HRV vaccine) | Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 90 U/mL. |
| Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Immunogenicity was assessed using ELISA technique in terms of seropositivity against PT, FHA and PRN antibodies. The cut-offs for antibodies were the Lower Limit Of Quantification (LLOQ) of the assays which were ≥ 2.693 IU/mL (anti-PT), ≥ 2.046 IU/mL (anti-FHA) and ≥ 2.187 IU/mL (anti-PRN). The Limit of Quantification is the lowest analyte concentration that can be quantitatively detected with a stated accuracy and precision, and LLOQ is the lowest standard curve point obtained by extrapolation, that can still be used for quantification. |
| Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Immunogenicity was assessed using ELISA technique in terms of seropositivity against Pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) antibodies. The cut-off used was ≥ 0.35 µg/mL. |
| Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Antibody concentrations against diphtheria and tetanus were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. |
| Immunogenicity in Terms of Anti-PRP Antibody Concentrations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Antibody concentrations against PRP were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. |
| Immunogenicity in Terms of Anti-HBs Antibody Concentrations. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Antibody concentrations against Hepatitis B were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. |
| Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | At Month 5 (One month after Dose 3 of co-administered vaccines) | Antibody concentrations against Poliovirus types 1, 2 and 3 were determined and expressed as Geometric Mean Titers (GMTs). |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 48 centers in the United States (US).
Pre-assignment details
Out of 1280 subjects enrolled in the study, 7 subjects did not receive any study treatment and 1 subject was eliminated from all analyses as there was a deviation in informed consent. 1272 subjects were vaccinated and included in the Exposed Set, 1148 subjects completed the study.
Participants by arm
| Arm | Count |
|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group Healthy female or male subjects, between and including 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in PCV-free liquid formulation, according to a 0, 2-month schedule, co-administered with one dose of each Pediarix, Hiberix and Prevnar-13 at three timepoints (day 1, month 2 and month 4). PCV-free implies no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. | 632 |
| HRV Lyophilized Group Healthy female or male subjects, between and including 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in lyophilized formulation, according to a 0, 2-month schedule, co-administered with one dose of each Pediarix, Hiberix and Prevnar-13 at three timepoints (day 1, month 2 and month 4). | 640 |
| Total | 1,272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | CONSENT WITHDRAWAL, NOT DUE TO AN AE | 11 | 13 |
| Overall Study | Lost to Follow-up | 21 | 29 |
| Overall Study | MIGRATED / MOVED FROM THE STUDY AREA | 7 | 10 |
| Overall Study | NOT WILLING / NOT ABLE TO BE CONTACTED | 1 | 2 |
| Overall Study | NOT WILLING TO PARTICIPATE THIS VISIT | 10 | 5 |
| Overall Study | OTHER, NOT SPECIFIED | 5 | 4 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | HRV Lyophilized Group | Total | HRV Porcine Circovirus (PCV)-Free Liquid Group |
|---|---|---|---|
| Age, Continuous | 8.7 Weeks STANDARD_DEVIATION 1.1 | 8.7 Weeks STANDARD_DEVIATION 1.1 | 8.7 Weeks STANDARD_DEVIATION 1.1 |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 7 Participants | 15 Participants | 8 Participants |
| Race/Ethnicity, Customized Asian | 22 Participants | 42 Participants | 20 Participants |
| Race/Ethnicity, Customized Black Or African American | 78 Participants | 152 Participants | 74 Participants |
| Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Other, not specified | 60 Participants | 120 Participants | 60 Participants |
| Race/Ethnicity, Customized White | 471 Participants | 939 Participants | 468 Participants |
| Sex: Female, Male Female | 309 Participants | 617 Participants | 308 Participants |
| Sex: Female, Male Male | 331 Participants | 655 Participants | 324 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 632 | 0 / 640 |
| other Total, other adverse events | 571 / 632 | 589 / 640 |
| serious Total, serious adverse events | 20 / 632 | 19 / 640 |
Outcome results
Primary
Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations.
Antibody concentrations against PT, FHA and PRN were determined and expressed as Geometric Mean Concentrations (GMCs).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | Anti-PT | 51 IU/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | Anti-FHA | 107.3 IU/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | Anti-PRN | 55 IU/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | Anti-PT | 54.2 IU/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | Anti-FHA | 107.7 IU/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibody Concentrations. | Anti-PRN | 56.6 IU/mL |
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for anti-PT antibodies.95% CI: [0.86, 1.03]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for anti-FHA antibodies.95% CI: [0.92, 1.08]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for anti-PRN antibodies.95% CI: [0.86, 1.1]ANOVA
Primary
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations.
Antibody concentrations against pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) were determined and expressed as GMCs in micrograms per milliliter (µg/mL).The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 4 | 1.24 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 9V | 1.68 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 6A | 2.84 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 14 | 6.27 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 3 | 0.53 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 18C | 1.81 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 6B | 1.93 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 19A | 1.87 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 5 | 1.28 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 19F | 2.94 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 7F | 3.01 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 23F | 1.14 µg/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 1 | 1.95 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 23F | 1.16 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 1 | 1.89 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 3 | 0.53 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 4 | 1.25 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 5 | 1.22 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 6A | 2.8 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 6B | 2 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 7F | 3.04 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 9V | 1.63 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 14 | 6.26 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 18C | 1.76 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 19A | 1.8 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. | Anti-PnPS 19F | 2.85 µg/mL |
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 1.95% CI: [0.93, 1.14]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 3.95% CI: [0.91, 1.11]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 4.95% CI: [0.9, 1.09]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 5.95% CI: [0.94, 1.17]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 6A.95% CI: [0.92, 1.12]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 6B.95% CI: [0.83, 1.12]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 7F.95% CI: [0.91, 1.08]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 9V.95% CI: [0.93, 1.14]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 14.95% CI: [0.89, 1.13]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 18C.95% CI: [0.92, 1.14]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 19A.95% CI: [0.93, 1.15]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 19F.95% CI: [0.95, 1.12]ANOVA
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of GMC ratios for Streptococcus pneumoniae (S. pneumoniae) serotype 23F.95% CI: [0.87, 1.1]ANOVA
Primary
Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value.
Immunogenicity was assessed using Enzyme Linked Immunosorbent Assay (ELISA) in terms of seroprotection rates against diphtheria toxoid. A seroprotected subject is a subject whose antibody concentration is greater than or equal to (≥) the level defining clinical protection. The following seroprotection thresholds were applicable:anti-D antibody concentrations ≥ 0.1 International Units/milliliter (IU/mL), anti-T antibody concentrations ≥ 0.1 IU/mL.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the Per protocol set (PPS) for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value. | Anti-D | 478 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value. | Anti-T | 486 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value. | Anti-D | 486 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Above or Equal to Cut-off Value. | Anti-T | 495 Participants |
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with seroprotective concentrations (≥ 0.1 IU/mL) of anti-D antibodies.95% CI: [-0.8, 0.79]
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with seroprotective concentrations (≥ 0.1 IU/mL) of anti-T antibodies.95% CI: [-0.79, 0.77]
Primary
Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value.
Immunogenicity was assessed using ChemiLuminescence ImmunoAssay (CLIA) in terms of seroprotection rates against Hepatitis B. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-HB antibody concentrations ≥ 10 milli International Units/milliliter (mIU/mL).
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value. | 457 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value. | 471 Participants |
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with seroprotective concentrations (≥ 10 mIU/mL) of anti-HB antibodies.95% CI: [-1.9, 0.16]
Primary
Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value.
Immunogenicity was assessed using virus micro-neutralization test in terms of seroprotection rates against polio virus types 1, 2 and 3. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-polio virus types 1, 2 and 3 types antibody titers ≥ 8 Estimated Dose 50% (ED50).
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | Anti-Polio 1 | 477 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | Anti-Polio 2 | 463 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | Anti-Polio 3 | 439 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | Anti-Polio 1 | 486 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | Anti-Polio 2 | 478 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-polio Virus Types 1, 2 and 3 Antibody Titers Above or Equal to Cut-off Value. | Anti-Polio 3 | 454 Participants |
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with seroprotective titers (≥ 8 ED50) of anti-poliovirus type 1 antibodies.95% CI: [-0.6, 1.15]
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with seroprotective titers (≥ 8 ED50) of anti-poliovirus type 2 antibodies.95% CI: [-1.02, 0.98]
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with seroprotective titers (≥ 8 ED50) of anti-poliovirus type 3 antibodies.95% CI: [-0.87, 0.84]
Primary
Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 0.15 µg/mL.
Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 0.15 µg/mL.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 0.15 µg/mL. | 473 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 0.15 µg/mL. | 479 Participants |
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with concentrations (≥ 0.15 µg/mL) of anti-PRP antibodies.95% CI: [-1.94, 2.28]
Primary
Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 1.0 µg/mL.
Immunogenicity was assessed in terms of seroprotection rates against PRP antibodies. A seroprotected subject is a subject whose antibody concentration is ≥ the level defining clinical protection. The following seroprotection thresholds were applicable:anti-PRP antibody concentrations ≥ 1.0 µg/mL.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 1.0 µg/mL. | 394 Participants |
| HRV Lyophilized Group | Number of Seroprotected Subjects With Anti-polyribosyl Ribitol Phosphate (Anti-PRP) Antibody Concentrations Above or Equal to Cut-off Value of 1.0 µg/mL. | 404 Participants |
Comparison: Non-inferiority of the immune responses to 3 doses of Pediarix, Hiberix and Prevenar 13 when co-administered with 2 doses of the PCV-free liquid HRV vaccine, as compared to when co-administered with lyophilized HRV vaccine in terms of group difference in percentage of subjects with concentrations (≥ 1.0 µg/mL) of anti-PRP antibodies.95% CI: [-5.75, 3.99]
Primary
Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies.
Seroresponse is defined as the percentage of subjects showing an antibody concentration above a threshold that leads to 95% seroresponse in the HRV lyophilized Group. The cut-offs used were as follows: anti-PT (18.566 IU/mL), anti-FHA (35.711 IU/mL) and anti-PRN (11.034 IU/mL).
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | Anti-PT | 440 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | Anti-FHA | 466 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | Anti-PRN | 455 Participants |
| HRV Lyophilized Group | Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | Anti-PT | 470 Participants |
| HRV Lyophilized Group | Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | Anti-FHA | 470 Participants |
| HRV Lyophilized Group | Number of Subjects With Seroresponse to Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. | Anti-PRN | 470 Participants |
Comparison: To rule out 10% decrease in seroresponse to PT antigen in subjects who received Pediarix co-administered with PCV-free-Liquid-HRV vaccine compared to subjects who received Pediarix co-administered with currently licensed lyophilized HRV vaccine where seroresponse was defined as percentage of subjects who showed a concentration above a threshold that led to 95% seroresponse in HRV lyophilized group.p-value: <0.0001t-test, 1 sided
Comparison: To rule out 10% decrease in seroresponse to FHA antigen in subjects who received Pediarix co-administered with PCV-free-Liquid-HRV vaccine compared to subjects who received Pediarix co-administered with currently licensed lyophilized HRV vaccine where seroresponse was defined as percentage of subjects who showed a concentration above a threshold that led to 95% seroresponse in HRV lyophilized group.p-value: <0.0001t-test, 1 sided
Comparison: To rule out 10% decrease in seroresponse to PRN antigen in subjects who received Pediarix co-administered with PCV-free-Liquid-HRV vaccine compared to subjects who received Pediarix co-administered with currently licensed lyophilized HRV vaccine where seroresponse was defined as percentage of subjects who showed a concentration above a threshold that led to 95% seroresponse in HRV lyophilized group.p-value: <0.0001t-test, 1 sided
Secondary
Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations.
Antibody concentrations against diphtheria and tetanus were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. | Anti-D | 1.85 IU/mL |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. | Anti-T | 1.88 IU/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. | Anti-D | 1.88 IU/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. | Anti-T | 1.86 IU/mL |
Secondary
Immunogenicity in Terms of Anti-HBs Antibody Concentrations.
Antibody concentrations against Hepatitis B were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-HBs Antibody Concentrations. | 2031.3 mIU/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-HBs Antibody Concentrations. | 2168.9 mIU/mL |
Secondary
Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers.
Antibody concentrations against Poliovirus types 1, 2 and 3 were determined and expressed as Geometric Mean Titers (GMTs).
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | Anti-Polio 1 | 747.2 Titers |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | Anti-Polio 2 | 659.6 Titers |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | Anti-Polio 3 | 1228.7 Titers |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | Anti-Polio 1 | 728.2 Titers |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | Anti-Polio 2 | 699.3 Titers |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. | Anti-Polio 3 | 1291.6 Titers |
Secondary
Immunogenicity in Terms of Anti-PRP Antibody Concentrations.
Antibody concentrations against PRP were determined and expressed as GMCs. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Immunogenicity in Terms of Anti-PRP Antibody Concentrations. | 4.41 µg/mL |
| HRV Lyophilized Group | Immunogenicity in Terms of Anti-PRP Antibody Concentrations. | 4.28 µg/mL |
Secondary
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value.
Immunogenicity was assessed using ELISA technique in terms of seropositivity against Pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) antibodies. The cut-off used was ≥ 0.35 µg/mL.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 23F | 409 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 1 | 442 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 3 | 317 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 4 | 434 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 5 | 409 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 6A | 441 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 6B | 407 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 7F | 448 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 9V | 431 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 14 | 441 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 18C | 436 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 19A | 438 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 19F | 448 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 18C | 451 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 7F | 466 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 1 | 463 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 19F | 465 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 3 | 322 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 9V | 454 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 4 | 453 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 19A | 458 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 5 | 424 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 14 | 454 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 6A | 461 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 23F | 425 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PnPS 6B | 434 Participants |
Secondary
Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value.
Immunogenicity was assessed using ELISA technique in terms of seropositivity against PT, FHA and PRN antibodies. The cut-offs for antibodies were the Lower Limit Of Quantification (LLOQ) of the assays which were ≥ 2.693 IU/mL (anti-PT), ≥ 2.046 IU/mL (anti-FHA) and ≥ 2.187 IU/mL (anti-PRN). The Limit of Quantification is the lowest analyte concentration that can be quantitatively detected with a stated accuracy and precision, and LLOQ is the lowest standard curve point obtained by extrapolation, that can still be used for quantification.
Time frame: At Month 5 (One month after Dose 3 of co-administered vaccines)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PT | 485 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | Anti-FHA | 486 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PRN | 486 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PT | 495 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | Anti-FHA | 495 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-PT, Anti-FHA and Anti-PRN Antibody Concentrations Above or Equal to Cut-off Value. | Anti-PRN | 495 Participants |
Secondary
Number of Seropositive Subjects With Anti-Rota Virus Immunoglobulin A (Anti-RV IgA) Antibody Concentrations Above or Equal to Cut-off Value of 20 Units/Milliliter (U/mL).
Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 20 U/mL.
Time frame: At Month 5 (Three months after Dose 2 of HRV vaccine)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-Rota Virus Immunoglobulin A (Anti-RV IgA) Antibody Concentrations Above or Equal to Cut-off Value of 20 Units/Milliliter (U/mL). | 318 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-Rota Virus Immunoglobulin A (Anti-RV IgA) Antibody Concentrations Above or Equal to Cut-off Value of 20 Units/Milliliter (U/mL). | 336 Participants |
Secondary
Number of Seropositive Subjects With Anti-RV IgA Antibody Concentrations Above or Equal to Cut-off Value of 90 U/mL.
Immunogenicity was assessed in terms of seropositivity against Rota virus IgA antibodies. The cut off used was ≥ 90 U/mL.
Time frame: At Month 5 (Three months after Dose 2 of HRV vaccine)
Population: Analysis was performed on the PPS for immunogenicity which included all vaccinated subjects for whom immunogenicity data were available, who complied with the procedures and intervals defined in the protocol and for whom assay results were available for antibodies against at least one routine infant vaccine antigen component.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Seropositive Subjects With Anti-RV IgA Antibody Concentrations Above or Equal to Cut-off Value of 90 U/mL. | 219 Participants |
| HRV Lyophilized Group | Number of Seropositive Subjects With Anti-RV IgA Antibody Concentrations Above or Equal to Cut-off Value of 90 U/mL. | 238 Participants |
Secondary
Number of Subjects With Any Serious Adverse Events (SAEs).
SAEs assessed include any untoward medical occurrence that resulted in death, were life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity.
Time frame: During the entire study period (Day 1 to Month 10)
Population: Analysis was performed on the Exposed set (ES). The ES included all subjects with at least one study vaccine administration documented. A safety analysis based on the ES included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Serious Adverse Events (SAEs). | 20 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Serious Adverse Events (SAEs). | 19 Participants |
Secondary
Number of Subjects With Any Solicited General Adverse Events (AEs).
Assessed solicited general AEs were cough/runny nose; diarrhoea; fever measured by 3 routes which were oral, axillary and rectal, defined as temperature ≥ 38.0 degrees Celsius (°C); irritability; loss of appetite and vomiting. Any = any solicited general AE irrespective of its intensity grade and relationship to vaccination
Time frame: During the 8-day (Days 1-8) follow-up period after each HRV vaccination.
Population: Analysis was performed on the Exposed set (ES). The ES included all subjects with at least one study vaccine administration documented. A safety analysis based on the ES included all vaccinated subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Cough / Runny Nose (Dose 2), Any | 224 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Cough / Runny Nose (Dose 1), Any | 172 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Cough / Runny Nose (Across doses), Any | 305 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Diarrhea (Dose 1), Any | 39 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Diarrhea (Dose 2), Any | 34 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Diarrhea (Across doses), Any | 69 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Fever (Dose 1), ≥ 38.0°C | 36 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Fever (Dose 2), ≥ 38.0°C | 64 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Fever (Across doses), ≥ 38.0°C | 89 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Irritability / Fussiness (Dose 1), Any | 448 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Irritability / Fussiness (Dose 2), Any | 440 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Irritability / Fussiness (Across doses), Any | 523 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Loss of appetite (Dose 1), Any | 204 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Loss of appetite (Dose 2), Any | 179 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Loss of appetite (Across doses), Any | 292 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Vomiting (Dose 1), Any | 110 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Vomiting (Dose 2), Any | 83 Participants |
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Vomiting (Across doses), Any | 147 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Loss of appetite (Dose 2), Any | 178 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Cough / Runny Nose (Dose 1), Any | 180 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Irritability / Fussiness (Dose 1), Any | 458 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Cough / Runny Nose (Dose 2), Any | 222 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Vomiting (Across doses), Any | 148 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Cough / Runny Nose (Across doses), Any | 313 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Irritability / Fussiness (Dose 2), Any | 427 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Diarrhea (Dose 1), Any | 36 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Loss of appetite (Across doses), Any | 293 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Diarrhea (Dose 2), Any | 26 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Irritability / Fussiness (Across doses), Any | 522 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Diarrhea (Across doses), Any | 55 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Vomiting (Dose 2), Any | 78 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Fever (Dose 1), ≥ 38.0°C | 32 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Loss of appetite (Dose 1), Any | 214 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Fever (Dose 2), ≥ 38.0°C | 75 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Vomiting (Dose 1), Any | 105 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Fever (Across doses), ≥ 38.0°C | 95 Participants |
Secondary
Number of Subjects With Any Unsolicited AEs.
Unsolicited AEs assessed include any AE reported in addition to those solicited during the clinical study. Also any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms were reported as an unsolicited AE. Any= Any unsolicited AE irrespective of its intensity grade and relationship to vaccination.
Time frame: During the 31-day (Days 1-31) follow-up period after each HRV vaccination.
Population: Analysis was performed on the Exposed set (ES). The ES included all subjects with at least one study vaccine administration documented. A safety analysis based on the ES included all vaccinated subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV Porcine Circovirus (PCV)-Free Liquid Group | Number of Subjects With Any Unsolicited AEs. | 294 Participants |
| HRV Lyophilized Group | Number of Subjects With Any Unsolicited AEs. | 327 Participants |