Infections, Rotavirus, Rotavirus Vaccines
Conditions
Keywords
Safety, Healthy infants, Immunogenicity, Human Rotavirus (HRV)
Brief summary
The purpose of this study is to evaluate the clinical consistency of three production lots of the Porcine circovirus (PCV)-free liquid formulation of oral live attenuated human rotavirus (HRV) vaccine and to evaluate the PCV-free liquid formulation of HRV vaccine as compared to the currently licensed lyophilised formulation of the HRV vaccine in terms of immunogenicity, reactogenicity and safety when administered as a two-dose vaccination in healthy infants starting at age 6-12 weeks. No new subjects will be enrolled in the extension phase of the study.
Detailed description
* Experimental design: Phase IIIA, observer-blind, randomised (1:1:1:1), controlled, multi-centric, with four parallel groups and a staggered enrolment (Part A and Part B). * Duration of the study: The intended duration of the study, per subject, will be approximately 7-8 months including the 6 months of extended safety follow-up period after the last dose of HRV vaccine. * Epoch 001: Primary starting at Visit 1 (Day 0) and ending at the safety follow-up contact (Month 7-8). * Primary completion Date (PCD): Visit 3 (Month 2-4). * End of Study (EoS): Last testing results released of samples collected at Visit 3 or Last Subject Last Visit (LSLV) (Follow up contact at month 7-8). * Study Groups: * PCV-free HRV liquid formulation lot A (also referred to as Liq\_A Group) * PCV-free HRV liquid formulation lot B (also referred to as Liq\_B Group) * PCV-free HRV liquid formulation lot C (also referred to as Liq\_C Group) * GSK Biologicals' currently licensed lyophilised HRV formulation (also referred to as Lyo Group) * Control:active control-GSK Biologicals' currently licensed lyophilised HRV vaccine * Vaccination schedule: Two doses of HRV vaccine to be administered according to a 0, 1-2 month schedule according to the immunisation schedule for RV vaccine. Note that as a result of internal change in data standards terminology, the study data collected was converted to cDISC and the statistical analysis plan was amended accordingly. Day 0 in the study design was replaced by Day 1; consequently, Day n was replaced by Day n+1. Thus, the time frames (Day 0, Day n) of Outcome Measures described in this study record are different to that denoted in the full protocol document posted.
Interventions
BIOLOGICALHRV PCV-free liquid vaccine
Subjects will receive two doses of PCV-free HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally
BIOLOGICALRotarix
Subjects will receive two doses of currently licensed lyophilised HRV vaccine at 6 and 12 weeks of age. The vaccine will be administered orally
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
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. * Written informed consent obtained from the parent(s)/LAR(s) (Legally acceptable representatives) of the subject prior to performing any study specific procedure. * A male or female infant between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination. * Born full-term (i.e., between a gestation period of 37 weeks 0 days and 41 weeks 6 days). * 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 0), or planned use during the study period. * Chronic administration 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 in the period starting 30 days before the first dose of vaccine administration and ending at Visit 3, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study and other licensed routine childhood vaccinations. * 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. * 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 RV. * Previous confirmed occurrence of RVGE. * 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. * 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 (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) | Antibody concentrations against RV were determined as GMCs and expressed as U/mL. The analysis was assessed to demonstrate the immunogenicity of the PCV-free liquid HRV vaccine (individual HRV liquid groups) to that of the currently licensed lyophilised HRV vaccine in terms of serum anti-RV IgA antibody concentrations 1-2 months after Dose 2. |
| Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C) | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) | Antibody concentrations against Rota Virus (RV) were determined as Geometric Mean Antibody Concentration (GMC) and expressed as Units per milliliter (U/mL). |
| Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) | Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (\<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). For this outcome measure, the three groups (Liq\_A, Liq\_B & Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of seroconversion rates of 1-2 months after Dose 2. |
| Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) | Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (\<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). The analysis was assessed to demonstrate the immunogenicity of PCV-free liquid HRV vaccine as compared to the currently licensed lyophilised HRV vaccine (individual HRV liquid groups) in terms of seroconversion rates 1-2 months after Dose 2. |
| Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) | Antibody concentrations against RV were determined as GMCs and expressed as U/mL. For this outcome measure, the three groups (Liq\_A, Liq\_B & Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of antibody concentrations at 1-2 months after Dose 2. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group) | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) | Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the pooled HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. For this outcome measure, the three groups (Liq\_A, Liq\_B & Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunogenicity of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL, 1-2 months after Dose 2 |
| Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups) | At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries) | Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the individual HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. The analysis was performed to assess the immunogenicity of the PCV-free liquid HRV vaccine (pooled HRV liquid groups) and the currently licensed lyophilised HRV vaccine, in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL 1-2 months after Dose 2. |
| Number of Subjects With Any Solicited General Adverse Events (AEs). | During the 8 days (Day 1 to Day 8) follow-up period after each dose of HRV vaccine | Assessed solicited general AEs were cough/runny nose, diarrhea, fever (defined as temperature ≥ 38.0°C), irritability/fussiness, loss of appetite and vomiting. Any solicited general AE is defined as any occurrence of the specified symptom, irrespective of intensity grade and relationship to vaccination. |
| Number of Subjects With Any Unsolicited AEs. | During the 31 day (Day 1 to Day 31) follow-up period after HRV vaccination across doses | An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any is defined as the occurrence of any unsolicited AE irrespective of its intensity grade and relationship to vaccination. |
| Number of Subjects With Any Serious Adverse Events (SAEs) | During the entire study period (Day 1 to Month 7-8) | 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. |
Countries
Costa Rica, Finland, Germany, Japan, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
The study was conducted at 66 centers in 8 countries: 2 in Costa Rica, 10 in Finland, 6 in Germany, 7 in Japan, 6 in Republic of Korea, 9 in Spain, 6 in Taiwan and 20 in the United States (US).
Pre-assignment details
Among 1612 subjects enrolled in the study, 1600 were vaccinated and 1545 completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Liq_A Group Subjects who received two doses of PCV-free HRV liquid formulation of lot A at 6 and 12 weeks of age. | 400 |
| Liq_B Group Subjects who received two doses of PCV-free HRV liquid formulation of lot B at 6 and 12 weeks of age. | 396 |
| Liq_C Group Subjects who received two doses of PCV-free HRV liquid formulation of lot C at 6 and 12 weeks of age. | 402 |
| Lyo Control Group Subjects who received two doses of currently licensed lyophilised HRV vaccine, at 6 and 12 weeks of age. | 402 |
| Total | 1,600 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 7 | 10 | 8 | 7 |
| Overall Study | Migrated/moved from the study area | 2 | 1 | 2 | 1 |
| Overall Study | Other | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 | 7 | 3 |
Baseline characteristics
| Characteristic | Liq_A Group | Total | Lyo Control Group | Liq_C Group | Liq_B Group |
|---|---|---|---|---|---|
| Age, Continuous | 8.5 Weeks STANDARD_DEVIATION 1.5 | 8.4 Weeks STANDARD_DEVIATION 1.5 | 8.5 Weeks STANDARD_DEVIATION 1.5 | 8.4 Weeks STANDARD_DEVIATION 1.6 | 8.3 Weeks STANDARD_DEVIATION 1.5 |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 6 Participants | 16 Participants | 5 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 95 Participants | 384 Participants | 95 Participants | 98 Participants | 96 Participants |
| Race/Ethnicity, Customized Black Or African American | 6 Participants | 41 Participants | 13 Participants | 13 Participants | 9 Participants |
| Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 29 Participants | 113 Participants | 27 Participants | 26 Participants | 31 Participants |
| Race/Ethnicity, Customized White | 263 Participants | 1045 Participants | 262 Participants | 262 Participants | 258 Participants |
| Sex: Female, Male Female | 208 Participants | 814 Participants | 203 Participants | 205 Participants | 198 Participants |
| Sex: Female, Male Male | 192 Participants | 786 Participants | 199 Participants | 197 Participants | 198 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 400 | 0 / 396 | 0 / 402 | 0 / 402 |
| other Total, other adverse events | 333 / 400 | 242 / 396 | 338 / 402 | 338 / 402 |
| serious Total, serious adverse events | 21 / 400 | 18 / 396 | 21 / 402 | 18 / 402 |
Outcome results
Primary
Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C)
Antibody concentrations against Rota Virus (RV) were determined as Geometric Mean Antibody Concentration (GMC) and expressed as Units per milliliter (U/mL).
Time frame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Population: The analysis was performed on the Per-protocol analysis set (PPS) for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Liq_A Group | Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C) | 155.7 U/mL |
| Liq_B Group | Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C) | 147.3 U/mL |
| Liq_C Group | Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C) | 175.9 U/mL |
Comparison: GMC Ratio of Anti-RV IgA antibody for Liq\_A and Liq\_B groups was calculated using ANOVA model with vaccine groups and country as fixed effects.95% CI: [0.79, 1.44]ANOVA
Comparison: GMC Ratio of Anti-RV IgA antibody for Liq\_A and Liq\_C groups was calculated using ANOVA model with vaccine groups and country as fixed effects.95% CI: [0.65, 1.19]ANOVA
Comparison: GMC Ratio of Anti-RV IgA antibody for Liq\_B and Liq\_C groups was calculated using ANOVA model with vaccine groups and country as fixed effects.95% CI: [0.61, 1.11]ANOVA
Primary
Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group
Antibody concentrations against RV were determined as GMCs and expressed as U/mL. The analysis was assessed to demonstrate the immunogenicity of the PCV-free liquid HRV vaccine (individual HRV liquid groups) to that of the currently licensed lyophilised HRV vaccine in terms of serum anti-RV IgA antibody concentrations 1-2 months after Dose 2.
Time frame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Population: The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Liq_A Group | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 155.7 U/mL |
| Liq_B Group | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 147.3 U/mL |
| Liq_C Group | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 175.9 U/mL |
| Lyo Control Group | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 153.8 U/mL |
Primary
Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group
Antibody concentrations against RV were determined as GMCs and expressed as U/mL. For this outcome measure, the three groups (Liq\_A, Liq\_B & Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of antibody concentrations at 1-2 months after Dose 2.
Time frame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Population: The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Liq_A Group | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group | 159.2 U/mL |
| Liq_B Group | Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group | 153.8 U/mL |
Comparison: Non-inferiority of Liq\_Pool Group as compared to Lyo Control group in terms of the GMC ratio calculated using ANOVA model with vaccine groups and country as fixed effects95% CI: [0.82, 1.33]ANOVA
Primary
Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group
Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (\<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). The analysis was assessed to demonstrate the immunogenicity of PCV-free liquid HRV vaccine as compared to the currently licensed lyophilised HRV vaccine (individual HRV liquid groups) in terms of seroconversion rates 1-2 months after Dose 2.
Time frame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Population: The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liq_A Group | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 77.7 Percentage of subjects |
| Liq_B Group | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 77.6 Percentage of subjects |
| Liq_C Group | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 82.5 Percentage of subjects |
| Lyo Control Group | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group | 81.8 Percentage of subjects |
Primary
Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group
Seroconversion rate (SCR) was defined as the percentage of subjects who were initially seronegative (i.e., with anti-RV IgA antibody concentration less than (\<) 20 U/mL before the first dose of HRV vaccine) and developed anti-RV IgA antibody concentration greater than or equal to (≥) 20 U/mL at Month 2-4 (1-2 months after dose 2). SCR was analysed using Enzyme Linked Immunosorbent Assay (ELISA). For this outcome measure, the three groups (Liq\_A, Liq\_B & Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunological non-inferiority of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of seroconversion rates of 1-2 months after Dose 2.
Time frame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Population: The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liq_A Group | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group | 79.3 Percentage of subjects |
| Liq_B Group | Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group | 81.8 Percentage of subjects |
Comparison: Non-inferiority of Liq\_Pool group compared to Lyo Control group in terms of difference in % of subjects with anti-RV IgA titer ≥ specified cut off with its 2-sided 95% CI in initially seronegative subjects95% CI: [-7.15, 2.63]
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 7-8)
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) |
|---|---|---|
| Liq_A Group | Number of Subjects With Any Serious Adverse Events (SAEs) | 21 Participants |
| Liq_B Group | Number of Subjects With Any Serious Adverse Events (SAEs) | 18 Participants |
| Liq_C Group | Number of Subjects With Any Serious Adverse Events (SAEs) | 21 Participants |
| Lyo Control Group | Number of Subjects With Any Serious Adverse Events (SAEs) | 18 Participants |
Secondary
Number of Subjects With Any Solicited General Adverse Events (AEs).
Assessed solicited general AEs were cough/runny nose, diarrhea, fever (defined as temperature ≥ 38.0°C), irritability/fussiness, loss of appetite and vomiting. Any solicited general AE is defined as any occurrence of the specified symptom, irrespective of intensity grade and relationship to vaccination.
Time frame: During the 8 days (Day 1 to Day 8) follow-up period after each dose of HRV vaccine
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) |
|---|---|---|---|
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 2 | 114 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 2 | 92 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 1 | 14 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 1 | 24 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 1 | 97 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 2 | 191 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 1 | 226 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 2 | 25 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 1 | 93 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 1 | 39 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 2 | 36 Participants |
| Liq_A Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 2 | 7 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 1 | 93 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 1 | 91 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 2 | 100 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 1 | 13 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 1 | 22 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 2 | 36 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 1 | 214 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 2 | 189 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 2 | 12 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 2 | 84 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 1 | 51 Participants |
| Liq_B Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 2 | 28 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 1 | 94 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 2 | 8 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 2 | 78 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 2 | 31 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 1 | 209 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 1 | 38 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 2 | 194 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 2 | 34 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 1 | 99 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 2 | 94 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 1 | 8 Participants |
| Liq_C Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 1 | 20 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 1 | 102 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 1 | 96 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 2 | 11 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Cough / Runny Nose - Dose 2 | 109 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Loss of appetite - Dose 2 | 94 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 1 | 216 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 2 | 32 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 2 | 34 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Fever (≥ 38.0°C) - Dose 1 | 23 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Irritability / Fussiness - Dose 2 | 194 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Diarrhea - Dose 1 | 10 Participants |
| Lyo Control Group | Number of Subjects With Any Solicited General Adverse Events (AEs). | Any - Vomiting - Dose 1 | 42 Participants |
Secondary
Number of Subjects With Any Unsolicited AEs.
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any is defined as the occurrence of any unsolicited AE irrespective of its intensity grade and relationship to vaccination.
Time frame: During the 31 day (Day 1 to Day 31) follow-up period after HRV vaccination across doses
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) |
|---|---|---|
| Liq_A Group | Number of Subjects With Any Unsolicited AEs. | 183 Participants |
| Liq_B Group | Number of Subjects With Any Unsolicited AEs. | 189 Participants |
| Liq_C Group | Number of Subjects With Any Unsolicited AEs. | 200 Participants |
| Lyo Control Group | Number of Subjects With Any Unsolicited AEs. | 184 Participants |
Secondary
Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups)
Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the individual HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. The analysis was performed to assess the immunogenicity of the PCV-free liquid HRV vaccine (pooled HRV liquid groups) and the currently licensed lyophilised HRV vaccine, in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL 1-2 months after Dose 2.
Time frame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Population: The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liq_A Group | Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups) | 62.7 Percentage of subjects |
| Liq_B Group | Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups) | 61.0 Percentage of subjects |
| Liq_C Group | Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups) | 65.3 Percentage of subjects |
| Lyo Control Group | Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups) | 62.3 Percentage of subjects |
Secondary
Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group)
Antibody concentrations ≥90 U/mL were determined and expressed as GMCs, assessed for the pooled HRV liquid groups and Control Group. The GMC calculations were performed by taking the anti-log of the mean of the log concentration transformations. For this outcome measure, the three groups (Liq\_A, Liq\_B & Liq\_C) were pooled into a single group (Liq\_Pool group) as they all received PCV free-liquid HRV vaccine, and as pre-specified in the protocol, the immunogenicity of the Liq\_Pool group was compared to the currently licensed lyophilized HRV vaccine (Lyo\_Control group) in terms of percentage of subjects with anti-RV IgA antibody concentrations ≥ 90 U/mL, 1-2 months after Dose 2
Time frame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Population: The analysis was performed on the PPS for immunogenicity that included all subjects who received both doses of study vaccine and for whom the liquid HRV vaccine or control vaccine was administered according to protocol and for whom immunogenicity data were available at the post-vaccination sampling time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liq_A Group | Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group) | 63.0 Percentage of subjects |
| Liq_B Group | Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group) | 62.3 Percentage of subjects |