Study to Assess the Efficacy, Immunogenicity and Safety of Liquid Human Rotavirus Vaccine, in Healthy Chinese Infants

A gastroenteritis episode was classified positive for rotavirus (RV) and caused by the circulating wild-type (WT) RV strains if RV other than the vaccine strain was identified in a stool sample collected during the episode. Severe RVGE was defined as an episode of RV GE with score equal to or higher than (\>=) 11 on a 20-point Vesikari scoring system.

Time frame: From Month 1 ½ to Month 21

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included subjects vaccinated with Rotarix™ vaccine or placebo who had entered the efficacy surveillance period (Months 1 ½-21) with no rotavirus other than vaccine strain in the gastroenteritis stool samples collected between Day 0 and Month 1 ½.

Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off assay (≥ 0.1 IU/mL). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo.

Time frame: At Day 0 and at Month 4

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

Concentrations were expressed as geometric mean concentrations (GMCs), in units per milliliter (U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 20 U/mL).

Time frame: At Day 0, Month 2 and at 12 months of age

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity Sub-cohort 1, which included subjects vaccinated with at least 1 dose of HRV vaccine/Placebo, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

Concentrations were expressed as geometric mean concentrations (GMCs), in units per milliliter (U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 20 U/mL).

Time frame: At Day 0, Month 2 and at 12 months of age

Population: Analysis was performed on the ATP cohort for immunogenicity, which included eligible subjects in the ATP cohorts for immunogenicity sub-cohorts 1 and 2 seronegative for serum anti-rotavirus immunoglobulin A (IgA) antibodies at Day 0 and with availability immunogenicity data at pre and post sampling time-points.

Concentrations were expressed as geometric mean concentrations (GMCs), in units per milliliter (U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 20 U/mL).

Time frame: At Day 0, Month 2 and at 12 months of age.

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

Antibody assessment was performed by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 5 EL.U/mL) for all antibodies assessed (anti-PT, anti-FHA and anti-PRN). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo.

Time frame: At Day 0 and at Month 4

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

A seroconverted subject was defined as a subject seronegative at baseline (Day 0) with the appearance of anti-RV IgA antibody concentration greater than or equal to (≥) 20 units per milliliter (U/mL) at the time point assessed. A seronegative subject was defined as a subject with anti-RV IgA antibody concentration lower than (\<) 20 U/mL.

Time frame: At Month 2 and at 12 months of age

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity Sub-cohort 1, which included subjects vaccinated with at least 1 dose of HRV vaccine/Placebo, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

A seroconverted subject was defined as a subject seronegative at baseline (Day 0) with the appearance of anti-RV IgA antibody concentration greater than or equal to (≥) 20 units per milliliter (U/mL) at the time point assessed. A seronegative subject was defined as a subject with anti-RV IgA antibody concentration lower than (\<) 20 U/mL.

Time frame: At Month 2 and at 12 months of age

Population: Analysis was performed on the ATP cohort for immunogenicity, which included eligible subjects in the ATP cohorts for immunogenicity sub-cohorts 1 and 2 seronegative for serum anti-rotavirus immunoglobulin A (IgA) antibodies at Day 0 and with availability immunogenicity data at pre and post sampling time-points.

A seroconverted subject was defined as a subject seronegative at baseline (Day 0) with the appearance of anti-RV IgA antibody concentration greater than or equal to (≥) 20 units per milliliter (U/mL) at the time point assessed. A seronegative subject was defined as a subject with anti-RV IgA antibody concentration lower than (\<) 20 U/mL.

Time frame: At Month 2 and at 12 months of age

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

Antibody assessment was performed by enzyme-linked immunosorbent assay (ELISA). A subject seropositive for anti-PT/anti-FHA/anti-PRN antibodies was defined as a subject with an anti-PT/anti-FHA/anti-PRN antibody concentrations greater than or equal to (≥) 5 ELISA units per milliliter (EL.U/mL). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo.

Time frame: At Day 0 and at Month 4

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

A subject seropositive for anti-rotavirus (anti-RV) immunoglobulin A (IgA) antibodies was defined as a subject anti-RV IgA antibody concentration greater than or equal to (≥) the seropositivity cut-off of 20 units per milliliter (U/mL).

Time frame: At Day 0, Month 2 and at 12 months of age

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

A subject seropositive for anti-rotavirus (anti-RV) immunoglobulin A (IgA) antibodies was defined as a subject anti-RV IgA antibody concentration greater than or equal to (≥) the seropositivity cut-off of 20 units per milliliter (U/mL).

Time frame: At Day 0, Month 2 and at 12 months of age

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity Sub-cohort 1, which included subjects vaccinated with at least 1 dose of HRV vaccine/Placebo, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

A subject seropositive for anti-rotavirus (anti-RV) immunoglobulin A (IgA) antibodies was defined as a subject anti-RV IgA antibody concentration greater than or equal to (≥) the seropositivity cut-off of 20 units per milliliter (U/mL).

Time frame: At Day 0, Month 2 and at 12 months of age

Population: Analysis was performed on the ATP cohort for immunogenicity, which included eligible subjects in the ATP cohorts for immunogenicity sub-cohorts 1 and 2 seronegative for serum anti-rotavirus immunoglobulin A (IgA) antibodies at Day 0 and with availability immunogenicity data at pre and post sampling time-points.

A subject seroprotected against diphtheria/tetanus was defined as a subject with an anti-diphtheria (anti-D)/anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo

Time frame: At Day 0 and at Month 4

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

A subject seroprotected against poliovirus types 1, 2 and 3 was defined as a subject with anti-poliovirus type 1 (anti-polio 1)/anti-polio 2/anti-polio 3 antibody titer greater than or equal to (≥) 8 estimated doses 50% (ED50). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo (cf. population definition below).

Time frame: At Day 0 and at Month 4

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.

Severe GE was defined as an episode of GE with score equal to or higher than (\>=) 11 on a 20-point Vesikari scoring system. This outcome measure concerns results for GE episodes due to any cause.

Time frame: From Month 1 ½ to Month 21

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included subjects vaccinated with Rotarix™ vaccine or placebo who had entered the efficacy surveillance period (Months 1 ½-21) with no rotavirus other than vaccine strain in the gastroenteritis stool samples collected between Day 0 and Month 1 ½.

A gastroenteritis episode was classified positive for rotavirus (RV) and caused by the circulating wild-type (WT) RV strains if RV other than the vaccine strain was identified in a stool sample collected during the episode.

Time frame: From Month 1 ½ to Month 21

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included subjects vaccinated with Rotarix™ vaccine or placebo who had entered the efficacy surveillance period (Months 1 ½-21) with no rotavirus other than vaccine strain in the gastroenteritis stool samples collected between Day 0 and Month 1 ½.

A gastroenteritis episode was classified positive for rotavirus (RV) if RV was identified in a stool sample collected during the episode. RV types assessed were G1 Wild Type (G1WT), G2, G3, G9, GX (G type unknown, but not vaccine strain), P4, P8 Wild Type (P8WT), P9, PX (P type unknown, but not vaccine strain) and Pooled Non-G1WT.

Time frame: From Month 1 ½ to Month 21

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included subjects vaccinated with Rotarix™ vaccine or placebo who had entered the efficacy surveillance period (Months 1 ½-21) with no rotavirus other than vaccine strain in the gastroenteritis stool samples collected between Day 0 and Month 1 ½.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, or result in disability/incapacity. Any = occurrence of an SAE regardless of the intensity grade or relationship to vaccination.

Time frame: Throughout the entire study period (from Day 0 to Study End at Month 21)

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one dose of the Rotarix™ vaccine or placebo administration documented.

Solicited general symptoms assessed following administration of the co-administered EPI vaccines were drowsiness, gastrointestinal symptoms, fussiness/irritability, loss of appetite, and fever, defined as axillary temperature (T) above or equal to \[\>=\] 37.5 degrees Celsius \[°C\] (if GSK scale) or \>= 37.1°C (if Chinese scale ). Any = any occurrence of the specified solicited general symptom regardless of the intensity grade or relationship to vaccination. This outcome measure was only assessed in subjects from Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo.

Time frame: Within the 8-day (Days 0-7) follow-up periods following Doses 1 and 2 of the OPV vaccine and Dose 1 of the Infanrix vaccine

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one dose of the Rotarix™ vaccine or placebo administration documented only on subjects in sub-cohort 2, for whom results were available.

Assessed solicited general symptoms were fever,defined as axillary temperature (T) above or equal to \[\>=\] 37.5 degrees Celsius \[°C\] (if GSK scale) or \>= 37.1°C (if Chinese scale), fussiness/irritability, loss of appetite, cough/runny nose, diarrhea and vomiting. Any = any occurrence of the specified solicited general symptom regardless of the intensity grade or relationship to vaccination. This outcome measure was only assessed in subjects from Sub-cohort 1, who received the EPI vaccination independently of study vaccination with the Rotarix vaccine/placebo.

Time frame: Within the 8-day (Days 0-7) follow-up periods after any dose of Rotarix vaccine/placebo

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one dose of the Rotarix™ vaccine or placebo administration documented, solely on subjects not part of Sub-cohort 2.

Solicited local symptoms assessed following administration of the co-administered EPI vaccines were pain, swelling, and redness. Any = any occurrence of the specified solicited local symptom regardless of the intensity grade. This outcome measure was only assessed in subjects from Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo.

Time frame: Within the 8-day (Days 0-7) follow-up periods following Dose 2 of the Rotarix vaccine/placebo

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one dose of the Rotarix™ vaccine or placebo administration documented only on subjects in sub-cohort 2, for whom results were available.

An unsolicited AE is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = occurrence of an unsolicited AE regardless of the intensity grade or relationship to vaccination.

Time frame: Within the 31-day (Days 0-30) follow-up periods following any dose of the Rotarix vaccine or placebo

Population: The analysis was performed on the Total Vaccinated cohort, which included all subjects with at least one dose of the Rotarix™ vaccine or placebo administration documented.

A gastroenteritis episode was classified positive for rotavirus (RV) and caused by the circulating WT RV strains if RV other than the vaccine strain was identified in a stool sample collected during the episode.

Time frame: From Month 1 ½ to Month 21

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included subjects vaccinated with Rotarix™ vaccine or placebo who had entered the efficacy surveillance period (Months 1 ½-21) with no rotavirus other than vaccine strain in the gastroenteritis stool samples collected between Day 0 and Month 1 ½.

A gastroenteritis episode was classified positive for rotavirus (RV) if RV was identified in a stool sample collected during the episode. Severe RVGE was defined as an episode of RVGE with score equal to or higher than (\>=) 11 on a 20-point Vesikari scoring system. RV types assessed were G1 Wild Type (G1WT), G2, G3, G9, GX (G type unknown, but not vaccine strain), P4, P8 Wild Type (P8WT), P9, PX (P type unknown, but not vaccine strain) and Pooled Non-G1WT.

Time frame: From Month 1 ½ to Month 21

Population: The analysis was performed on the According-to-Protocol cohort for efficacy, which included subjects vaccinated with Rotarix™ vaccine or placebo who had entered the efficacy surveillance period (Months 1 ½-21) with no rotavirus other than vaccine strain in the gastroenteritis stool samples collected between Day 0 and Month 1 ½.

Titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seroprotection cut-off (≥ 8 estimated doses 50% \[ED50\] for anti-poliovirus type 1 \[anti-polio 1\]/anti-polio 2/anti-polio 3 antibodies. This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix vaccine/placebo.

Time frame: At Day 0 and at Month 4

Population: Analysis was performed on the ATP cohort for immunogenicity Sub-cohort 2, which included subjects with OPV and Infanrix™ vaccines co-administered with the study vaccine, complying with protocol, with EPI childhood vaccinations completed according to Chinese recommendations and available immunogenicity data at post sampling time-point.