Trial Outcomes & Findings for This Study Will Evaluate the Immunogenicity, Reactogenicity and Safety of the Routine Infant Vaccines Pediarix®, Hiberix® and Prevenar 13® When Co-administered With GlaxoSmithKline (GSK) Biologicals' Liquid Human Rotavirus Vaccine (HRV) as Compared to GSK's Licensed Lyophilized Vaccine (NCT NCT03207750)

NCT ID: NCT03207750

Last Updated: 2020-12-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1280 participants

Primary outcome timeframe

At Month 5 (One month after Dose 3 of co-administered vaccines)

Results posted on

2020-12-29

Participant Flow

The study was conducted at 48 centers in the United States (US).

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.

Participant milestones

Participant milestones
Measure	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.	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).
Overall Study STARTED	632	640
Overall Study COMPLETED	574	574
Overall Study NOT COMPLETED	58	66

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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).
Overall Study Adverse Event	3	2
Overall Study Lost to Follow-up	21	29
Overall Study Protocol Violation	0	1
Overall Study CONSENT WITHDRAWAL, NOT DUE TO AN AE	11	13
Overall Study MIGRATED / MOVED FROM THE STUDY AREA	7	10
Overall Study NOT WILLING TO PARTICIPATE THIS VISIT	10	5
Overall Study NOT WILLING / NOT ABLE TO BE CONTACTED	1	2
Overall Study OTHER, NOT SPECIFIED	5	4

Baseline Characteristics

This Study Will Evaluate the Immunogenicity, Reactogenicity and Safety of the Routine Infant Vaccines Pediarix®, Hiberix® and Prevenar 13® When Co-administered With GlaxoSmithKline (GSK) Biologicals' Liquid Human Rotavirus Vaccine (HRV) as Compared to GSK's Licensed Lyophilized Vaccine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=632 Participants 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.	HRV Lyophilized Group n=640 Participants 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).	Total n=1272 Participants Total of all reporting groups
Age, Continuous	8.7 Weeks STANDARD_DEVIATION 1.1 • n=5 Participants	8.7 Weeks STANDARD_DEVIATION 1.1 • n=7 Participants	8.7 Weeks STANDARD_DEVIATION 1.1 • n=5 Participants
Sex: Female, Male Female	308 Participants n=5 Participants	309 Participants n=7 Participants	617 Participants n=5 Participants
Sex: Female, Male Male	324 Participants n=5 Participants	331 Participants n=7 Participants	655 Participants n=5 Participants
Race/Ethnicity, Customized American Indian Or Alaska Native	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized Asian	20 Participants n=5 Participants	22 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	74 Participants n=5 Participants	78 Participants n=7 Participants	152 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White	468 Participants n=5 Participants	471 Participants n=7 Participants	939 Participants n=5 Participants
Race/Ethnicity, Customized Other, not specified	60 Participants n=5 Participants	60 Participants n=7 Participants	120 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=486 Participants 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.	HRV Lyophilized Group n=495 Participants 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).
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	486 Participants
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	495 Participants

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=460 Participants 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.	HRV Lyophilized Group n=471 Participants 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).
Number of Seroprotected Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentrations Above or Equal to Cut-off Value.	457 Participants	471 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=477 Participants 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.	HRV Lyophilized Group n=487 Participants 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).
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	486 Participants
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	478 Participants
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	454 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=486 Participants 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.	HRV Lyophilized Group n=495 Participants 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).
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 Interval 47.8 to 54.5	54.2 IU/mL Interval 51.3 to 57.4
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 Interval 101.4 to 113.5	107.7 IU/mL Interval 101.6 to 114.1
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 Interval 50.1 to 60.4	56.6 IU/mL Interval 51.9 to 61.7

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=448 Participants 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.	HRV Lyophilized Group n=466 Participants 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).
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 1	1.95 µg/mL Interval 1.81 to 2.1	1.89 µg/mL Interval 1.76 to 2.03
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 3	0.53 µg/mL Interval 0.49 to 0.57	0.53 µg/mL Interval 0.49 to 0.57
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 4	1.24 µg/mL Interval 1.16 to 1.34	1.25 µg/mL Interval 1.18 to 1.34
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 5	1.28 µg/mL Interval 1.17 to 1.39	1.22 µg/mL Interval 1.13 to 1.31
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 6A	2.84 µg/mL Interval 2.64 to 3.05	2.8 µg/mL Interval 2.61 to 3.0
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 6B	1.93 µg/mL Interval 1.72 to 2.15	2 µg/mL Interval 1.8 to 2.22
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 7F	3.01 µg/mL Interval 2.83 to 3.21	3.04 µg/mL Interval 2.86 to 3.22
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 9V	1.68 µg/mL Interval 1.56 to 1.81	1.63 µg/mL Interval 1.52 to 1.75
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 14	6.27 µg/mL Interval 5.74 to 6.84	6.26 µg/mL Interval 5.75 to 6.82
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 18C	1.81 µg/mL Interval 1.68 to 1.95	1.76 µg/mL Interval 1.64 to 1.89
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 19A	1.87 µg/mL Interval 1.73 to 2.02	1.8 µg/mL Interval 1.68 to 1.93
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 19F	2.94 µg/mL Interval 2.76 to 3.12	2.85 µg/mL Interval 2.69 to 3.03
Immunogenicity in Terms of Anti-pneumococcal Serotypes (Anti-PnPS) Antibody Concentrations. Anti-PnPS 23F	1.14 µg/mL Interval 1.04 to 1.24	1.16 µg/mL Interval 1.07 to 1.26

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=485 Participants 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.	HRV Lyophilized Group n=492 Participants 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).
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	479 Participants

PRIMARY outcome

Timeframe: At Month 5 (One month after Dose 3 of co-administered vaccines)

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=485 Participants 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.	HRV Lyophilized Group n=492 Participants 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).
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	404 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=486 Participants 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.	HRV Lyophilized Group n=495 Participants 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).
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	470 Participants
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	470 Participants
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	470 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=417 Participants 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.	HRV Lyophilized Group n=426 Participants 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).
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	336 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=417 Participants 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.	HRV Lyophilized Group n=426 Participants 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).
Number of Seropositive Subjects With Anti-RV IgA Antibody Concentrations Above or Equal to Cut-off Value of 90 U/mL.	219 Participants	238 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=486 Participants 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.	HRV Lyophilized Group n=495 Participants 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).
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	495 Participants
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	495 Participants
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	495 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=448 Participants 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.	HRV Lyophilized Group n=466 Participants 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).
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 1	442 Participants	463 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 3	317 Participants	322 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 4	434 Participants	453 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 5	409 Participants	424 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 6A	441 Participants	461 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 6B	407 Participants	434 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 7F	448 Participants	466 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 9V	431 Participants	454 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 14	441 Participants	454 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 18C	436 Participants	451 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 19A	438 Participants	458 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 19F	448 Participants	465 Participants
Number of Seropositive Subjects With Anti-PnPS Antibody Concentrations Above or Equal to Cut-off Value. Anti-PnPS 23F	409 Participants	425 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=486 Participants 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.	HRV Lyophilized Group n=495 Participants 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).
Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. Anti-D	1.85 IU/mL Interval 1.72 to 1.98	1.88 IU/mL Interval 1.75 to 2.02
Immunogenicity in Terms of Anti-D and Anti-T Antibody Concentrations. Anti-T	1.88 IU/mL Interval 1.75 to 2.02	1.86 IU/mL Interval 1.74 to 1.99

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=485 Participants 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.	HRV Lyophilized Group n=492 Participants 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).
Immunogenicity in Terms of Anti-PRP Antibody Concentrations.	4.41 µg/mL Interval 3.82 to 5.09	4.28 µg/mL Interval 3.71 to 4.94

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=460 Participants 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.	HRV Lyophilized Group n=471 Participants 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).
Immunogenicity in Terms of Anti-HBs Antibody Concentrations.	2031.3 mIU/mL Interval 1834.6 to 2249.0	2168.9 mIU/mL Interval 1977.5 to 2378.9

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=477 Participants 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.	HRV Lyophilized Group n=487 Participants 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).
Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. Anti-Polio 1	747.2 Titers Interval 673.5 to 828.8	728.2 Titers Interval 656.3 to 808.0
Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. Anti-Polio 2	659.6 Titers Interval 587.9 to 740.0	699.3 Titers Interval 627.7 to 779.0
Immunogenicity in Terms of Anti-poliovirus Types 1, 2 and 3 Antibody Titers. Anti-Polio 3	1228.7 Titers Interval 1100.3 to 1372.1	1291.6 Titers Interval 1159.1 to 1439.3

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=632 Participants 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.	HRV Lyophilized Group n=640 Participants 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).
Number of Subjects With Any Solicited General Adverse Events (AEs). Cough / Runny Nose (Dose 1), Any	172 Participants	180 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Cough / Runny Nose (Dose 2), Any	224 Participants	222 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Cough / Runny Nose (Across doses), Any	305 Participants	313 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Diarrhea (Dose 1), Any	39 Participants	36 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Diarrhea (Dose 2), Any	34 Participants	26 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Diarrhea (Across doses), Any	69 Participants	55 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Fever (Dose 1), ≥ 38.0°C	36 Participants	32 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Fever (Dose 2), ≥ 38.0°C	64 Participants	75 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Fever (Across doses), ≥ 38.0°C	89 Participants	95 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Irritability / Fussiness (Dose 1), Any	448 Participants	458 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Irritability / Fussiness (Dose 2), Any	440 Participants	427 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Irritability / Fussiness (Across doses), Any	523 Participants	522 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Loss of appetite (Dose 1), Any	204 Participants	214 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Loss of appetite (Dose 2), Any	179 Participants	178 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Loss of appetite (Across doses), Any	292 Participants	293 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Vomiting (Dose 1), Any	110 Participants	105 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Vomiting (Dose 2), Any	83 Participants	78 Participants
Number of Subjects With Any Solicited General Adverse Events (AEs). Vomiting (Across doses), Any	147 Participants	148 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=632 Participants 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.	HRV Lyophilized Group n=640 Participants 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).
Number of Subjects With Any Unsolicited AEs.	294 Participants	327 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	HRV Porcine Circovirus (PCV)-Free Liquid Group n=632 Participants 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.	HRV Lyophilized Group n=640 Participants 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).
Number of Subjects With Any Serious Adverse Events (SAEs).	20 Participants	19 Participants

Adverse Events

HRV Porcine Circovirus (PCV)-Free Liquid Group

Serious events: 20 serious events

Other events: 571 other events

Deaths: 1 deaths

HRV Lyophilized Group

Serious events: 19 serious events

Other events: 589 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER