Gastroenteritis
Conditions
Keywords
Rotavirus (RV), Human rotavirus (HRV), Rotarix Porcine circovirus (PCV)-free liquid, Rotarix liquid, Healthy Chinese infants, Immunogenicity, Reactogenicity, Safety
Brief summary
The purpose of this study is to evaluate the immunogenicity, reactogenicity and safety of the Porcine circovirus (PCV)-free liquid formulation of GlaxoSmithKline Biologicals' SA (GSK) oral live attenuated human rotavirus (HRV) study intervention compared to GSK's liquid oral live attenuated HRV study intervention in healthy Chinese infants 6 to 16 weeks of age at the time of the first study intervention administration.
Interventions
COMBINATION_PRODUCTGSK's liquid oral live attenuated HRV
2 doses of GSK's liquid oral live attenuated HRV study intervention administered orally at Day 1 and Month 1, according to the immunization schedule for HRV study intervention licensed outside of China.
COMBINATION_PRODUCTPCV-free liquid formulation of GSK's oral live attenuated HRV
2 doses of PCV-free liquid formulation of GSK's oral live attenuated HRV study intervention administered orally at Day 1 and Month 1, according to the immunization schedule for HRV study intervention licensed outside of China.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study will be conducted in an observer-blind manner.
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 16 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Participants' parent(s)/legally acceptable representative(s) \[LAR(s)\], who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure. * A male or female with Chinese origin, between, and including, 6 and 16 weeks (42-112 days) of age at the time of the first study intervention administration. * Healthy participants as established by medical history and clinical examination before entering into the study. * Born after a gestation period of 36 to 42 weeks inclusive.
Exclusion criteria
Medical conditions * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * History of severe combined immunodeficiency. * History of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention. * History of seizures or progressive neurological disease. * Family history of congenital or hereditary immunodeficiency. * Uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception (IS). * History of IS. * Major congenital defects, or serious chronic illness as assessed by the investigator. * Previous confirmed occurrence of rotavirus gastroenteritis (RVGE). * Participants with confirmed or suspected Coronavirus Disease 2019 (COVID-19). Prior/Concomitant therapy * Use of any investigational or non-registered product other than the study interventions during the period beginning 30 days before the first dose of study interventions (Day -29 to Day 1), or planned use 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 and ending 30 days after the second dose of study intervention administration\*, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study and other licensed routine childhood vaccinations. \*In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is organized by public health authorities outside the routine immunization programme, the time period described above can be reduced if, necessary for that mass vaccination vaccine, provided it is licensed and used according to its Product Information. * Administration of immunoglobulins and/or any blood products or plasma derivatives from birth or planned administration during the study period. * Administration of long-acting immune-modifying drugs from birth or planned administration at any time during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone \>= 0.5 milligram/kilogram (kg)/day, or equivalent. Inhaled and topical steroids are allowed. * Previous vaccination against RV. Prior/Concurrent clinical study experience \- Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine/product. Other exclusions \- Child in care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Anti-rotavirus (RV) Immunoglobulin A (IgA) Antibody (Ab) Seroconversion Rate | At Month 2 (1-month post-Dose 2) | Seroconversion rate is defined as the percentage of participants who were initially seronegative (i.e., with anti-RV IgA Ab concentration below \[\<\] 20 unit per milliliter \[U/mL\] prior the first dose of study intervention) and developed anti-RV IgA Ab concentration greater than or equal to (\>=) 20 U/mL at Month 2 (1-month post-Dose 2). |
| Serum Anti-RV IgA Ab Concentrations Expressed as Geometric Mean Concentrations (GMCs) | At Month 2 (1-month post-Dose 2) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serum Anti-RV IgA Ab Concentrations >= 90 U/mL | At Month 2 (1-month post-Dose 2) | — |
| Number of Participants Reporting Solicited Systemic Events | Within 14 days (the day of vaccination and 13 subsequent days) after each vaccination (occurring at Day 1 and Month 1) | Solicited systemic events include fever/pyrexia, diarrhoea, vomiting, irritability/fussiness, loss of appetite, cough/runny nose. Fever is defined as body temperature \>= 37.5 degrees Celsius (°C) and the preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination. |
| Number of Participants Reporting Unsolicited Adverse Events (AEs) | Within 31 days (the day of vaccination and 30 subsequent days) after each vaccination (occurring at Day 1 and Month 1) | Unsolicited AEs 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 is reported as an unsolicited adverse event. Any = occurrence the event regardless of intensity grade or relation to the study vaccination |
| Number of Participants Reporting Serious Adverse Events (SAEs) | From Day 1 to Month 7 | An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or in other situations that are considered serious as per medical or scientific judgment. Any = occurrence of the SAE regardless of intensity grade or relation to the study vaccination. |
Countries
China
Participant flow
Recruitment details
This study was conducted in China.
Pre-assignment details
One participant was randomized to the HRV group but was vaccinated in the HRV PCV-free group. Data for this participant was analyzed in the HRV PCV-free group for all analyses.
Participants by arm
| Arm | Count |
|---|---|
| Human Rotavirus (HRV) Group Participants received 2 doses of GSK's liquid oral live attenuated HRV study intervention at Day 1 and Month 1. | 998 |
| HRV Porcine Circovirus (PCV)-Free Group Participants received 2 doses of the PCV-free liquid formulation of GSK's oral live attenuated HRV study intervention at Day 1 and Month 1. | 1,002 |
| Total | 2,000 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 |
| Overall Study | Adverse Event Requiring Expedited Report | 1 | 0 |
| Overall Study | Migrated / Moved from the Study Area | 13 | 10 |
| Overall Study | Other | 23 | 19 |
Baseline characteristics
| Characteristic | Human Rotavirus (HRV) Group | HRV Porcine Circovirus (PCV)-Free Group | Total |
|---|---|---|---|
| Age, Continuous | 10.1 WEEKS STANDARD_DEVIATION 2.9 | 10.2 WEEKS STANDARD_DEVIATION 2.9 | 10.1 WEEKS STANDARD_DEVIATION 2.9 |
| Race/Ethnicity, Customized ASIAN - EAST ASIAN HERITAGE | 998 Participants | 1002 Participants | 2000 Participants |
| Sex: Female, Male Female | 455 Participants | 512 Participants | 967 Participants |
| Sex: Female, Male Male | 543 Participants | 490 Participants | 1033 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 998 | 0 / 1,002 |
| other Total, other adverse events | 596 / 998 | 617 / 1,002 |
| serious Total, serious adverse events | 251 / 998 | 262 / 1,002 |
Outcome results
Primary
Percentage of Participants With Anti-rotavirus (RV) Immunoglobulin A (IgA) Antibody (Ab) Seroconversion Rate
Seroconversion rate is defined as the percentage of participants who were initially seronegative (i.e., with anti-RV IgA Ab concentration below \[\<\] 20 unit per milliliter \[U/mL\] prior the first dose of study intervention) and developed anti-RV IgA Ab concentration greater than or equal to (\>=) 20 U/mL at Month 2 (1-month post-Dose 2).
Time frame: At Month 2 (1-month post-Dose 2)
Population: Analysis was performed on Per Protocol Set (PPS), which includes all participants who adhered to the study protocol, ensuring they received no unapproved treatments, remained blinded, had anti-RV concentration \<20 U/mL before intervention, had available anti-RV results at Month 2, complied with blood sampling schedules, and had no concurrent infections. Only participants with data available at specified timepoints were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Human Rotavirus (HRV) Group | Percentage of Participants With Anti-rotavirus (RV) Immunoglobulin A (IgA) Antibody (Ab) Seroconversion Rate | 88.7 Percentage of participants |
| HRV Porcine Circovirus (PCV)-Free Group | Percentage of Participants With Anti-rotavirus (RV) Immunoglobulin A (IgA) Antibody (Ab) Seroconversion Rate | 84.9 Percentage of participants |
Comparison: To demonstrate the immunological non-inferiority of HRV PCV-free Group as compared to HRV Group in terms of seroconversion rates 1 month post-Dose 2.95% CI: [-6.93, -0.55]
Primary
Serum Anti-RV IgA Ab Concentrations Expressed as Geometric Mean Concentrations (GMCs)
Time frame: At Month 2 (1-month post-Dose 2)
Population: Analysis was performed on PPS. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Human Rotavirus (HRV) Group | Serum Anti-RV IgA Ab Concentrations Expressed as Geometric Mean Concentrations (GMCs) | 222.82 U/mL |
| HRV Porcine Circovirus (PCV)-Free Group | Serum Anti-RV IgA Ab Concentrations Expressed as Geometric Mean Concentrations (GMCs) | 157.31 U/mL |
Comparison: To demonstrate the non-inferiority of the HRV PCV-free Group as compared to HRV Group in terms of serum anti-RV IgA Ab concentrations 1 month post-Dose 2.95% CI: [0.6, 0.84]
Secondary
Number of Participants Reporting Serious Adverse Events (SAEs)
An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization or results in disability/incapacity or in other situations that are considered serious as per medical or scientific judgment. Any = occurrence of the SAE regardless of intensity grade or relation to the study vaccination.
Time frame: From Day 1 to Month 7
Population: Analysis was performed on the Exposed Set which includes all participants with at least 1 dose of the study intervention administered and for whom SAE data were available after the corresponding vaccination for the specified timepoint. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Human Rotavirus (HRV) Group | Number of Participants Reporting Serious Adverse Events (SAEs) | 251 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Serious Adverse Events (SAEs) | 262 Participants |
Secondary
Number of Participants Reporting Solicited Systemic Events
Solicited systemic events include fever/pyrexia, diarrhoea, vomiting, irritability/fussiness, loss of appetite, cough/runny nose. Fever is defined as body temperature \>= 37.5 degrees Celsius (°C) and the preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade or relation to the study vaccination.
Time frame: Within 14 days (the day of vaccination and 13 subsequent days) after each vaccination (occurring at Day 1 and Month 1)
Population: Analysis was performed on the Exposed Set which includes all participants with at least 1 dose of the study intervention administered and with the solicited systemic events diary card data available after the corresponding vaccination for the specified timepoint. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Cough/Runny Nose, post vaccination at Day 1 | 158 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Cough/Runny Nose, post vaccination at Month 1 | 131 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Diarrhoea, post vaccination at Day 1 | 66 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Diarrhoea, post vaccination at Month 1 | 38 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Fever/Pyrexia, post vaccination at Day 1 | 122 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Fever/Pyrexia, post vaccination at Month 1 | 104 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Irritability/Fussiness, post vaccination at Day 1 | 126 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Irritability/Fussiness, post vaccination at Month 1 | 61 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Loss of appetite, post vaccination at Day 1 | 73 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Loss of appetite, post vaccination at Month 1 | 32 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Vomiting, post vaccination at Day 1 | 71 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Solicited Systemic Events | Vomiting, post vaccination at Month 1 | 30 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Vomiting, post vaccination at Day 1 | 69 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Cough/Runny Nose, post vaccination at Day 1 | 200 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Irritability/Fussiness, post vaccination at Day 1 | 150 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Cough/Runny Nose, post vaccination at Month 1 | 157 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Loss of appetite, post vaccination at Month 1 | 34 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Diarrhoea, post vaccination at Day 1 | 66 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Irritability/Fussiness, post vaccination at Month 1 | 59 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Diarrhoea, post vaccination at Month 1 | 40 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Vomiting, post vaccination at Month 1 | 36 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Fever/Pyrexia, post vaccination at Day 1 | 100 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Loss of appetite, post vaccination at Day 1 | 92 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Solicited Systemic Events | Fever/Pyrexia, post vaccination at Month 1 | 91 Participants |
Secondary
Number of Participants Reporting Unsolicited Adverse Events (AEs)
Unsolicited AEs 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 is reported as an unsolicited adverse event. Any = occurrence the event regardless of intensity grade or relation to the study vaccination
Time frame: Within 31 days (the day of vaccination and 30 subsequent days) after each vaccination (occurring at Day 1 and Month 1)
Population: Analysis was performed on the Exposed Set which includes all participants with at least 1 dose of the study intervention administered and for whom unsolicited AEs data were available after the corresponding vaccination for the specified timepoint. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Human Rotavirus (HRV) Group | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Post-vaccination at Month 1 | 223 Participants |
| Human Rotavirus (HRV) Group | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Post-vaccination at Day 1 | 236 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Post-vaccination at Day 1 | 234 Participants |
| HRV Porcine Circovirus (PCV)-Free Group | Number of Participants Reporting Unsolicited Adverse Events (AEs) | Post-vaccination at Month 1 | 229 Participants |
Secondary
Percentage of Participants With Serum Anti-RV IgA Ab Concentrations >= 90 U/mL
Time frame: At Month 2 (1-month post-Dose 2)
Population: Analysis was performed on PPS. Only participants with data available at the specified timepoints were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Human Rotavirus (HRV) Group | Percentage of Participants With Serum Anti-RV IgA Ab Concentrations >= 90 U/mL | 69.2 Percentage of participants |
| HRV Porcine Circovirus (PCV)-Free Group | Percentage of Participants With Serum Anti-RV IgA Ab Concentrations >= 90 U/mL | 62.9 Percentage of participants |
Comparison: To demonstrate the immunological non-inferiority of HRV PCV-free Group as compared to HRV Group in terms of percentage of participants with anti-RV IgA antibody concentrations \>=90 U/mL 1 month post-Dose 2.95% CI: [-10.81, -1.92]