Infections, Rotavirus, Rotavirus Vaccines
Conditions
Keywords
Gastroenteritis
Brief summary
The aim of this study is to assess the immunogenicity, reactogenicity and safety of the human rotavirus (HRV) Rotarix ™ vaccine when administered in healthy infants aged approximately 6-12 weeks at the time of first vaccination.
Interventions
BIOLOGICALRotarix ™
Two oral doses
BIOLOGICALPlacebo
Two oral doses
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. * A male or female between, and including, 6 to 12 weeks of age at the time of the first dose of the vaccination. * Written informed consent obtained from the parents or guardians of the subject. * Healthy subjects as established by medical history and clinical examination before entering into the study. * Born after a normal gestation period of between 37 and 41 weeks + 6 days inclusive. * Subjects for whom the vaccination history is available from vaccination diary cards or medical charts.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the dose of study vaccine, or planned use during the study period. * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. * Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine with the exception of the routine infant vaccines. * Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract or other serious medical condition as determined by the investigator. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Acute disease at the time of enrolment. * Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. * Gastroenteritis (GE) within 7 days preceding the study vaccine administration. * Previous confirmed occurrence of RV GE. * Previous vaccination with rotavirus vaccine or planned use during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A | One month after the second vaccine dose | Seroconversion is defined as the appearance of antibodies with concentrations greater than or equal to 20 units per milliliter (U/mL) in the serum of subjects seronegative before vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Anti-rotavirus Immunoglobulin A Antibody Concentrations | One month after the second vaccine dose | Concentrations are given as Geometric Mean Concentrations (GMCs). Note: In the Placebo Group the value was below the assay cut-off (20 units per milliliter). |
| Number of Subjects Reporting Solicited Symptoms | During the 8-day (Day 0 - Day 7) follow-up period after each vaccine dose. | Solicited symptoms assessed include cough, diarrhoea, irritability, loss of appetite , fever and vomiting. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | During the 31-day (Day 0 - Day 30) follow-up period after each vaccine dose | Unsolicited AE covers any AE 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. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | Throughout the study period (2-3 months). | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects Reporting Rotavirus Gastroenteritis Episode(s) | From Dose 1 up to 1 month after Dose 2. | — |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rotarix Group Subjects received 2 oral doses of Rotarix according to a 0, 1 or 2-month schedule. | 508 |
| Placebo Group Subjects received 2 oral doses of placebo according to a 0, 1 or 2-month schedule. | 176 |
| Total | 684 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Porcine circovirus detection in vaccine | 38 | 14 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Rotarix Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 8.8 Weeks STANDARD_DEVIATION 1.25 | 8.9 Weeks STANDARD_DEVIATION 1.26 | 8.8 Weeks STANDARD_DEVIATION 1.25 |
| Sex: Female, Male Female | 231 Participants | 79 Participants | 310 Participants |
| Sex: Female, Male Male | 277 Participants | 97 Participants | 374 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 367 / 508 | 134 / 176 |
| serious Total, serious adverse events | 17 / 508 | 13 / 176 |
Outcome results
Primary
Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A
Seroconversion is defined as the appearance of antibodies with concentrations greater than or equal to 20 units per milliliter (U/mL) in the serum of subjects seronegative before vaccination.
Time frame: One month after the second vaccine dose
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, on subjects with available results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A | 280 subjects |
| Placebo Group | Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A | 5 subjects |
Secondary
Number of Subjects Reporting Rotavirus Gastroenteritis Episode(s)
Time frame: From Dose 1 up to 1 month after Dose 2.
Population: Analysis was performed on the Total Vaccinated Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Rotavirus Gastroenteritis Episode(s) | 0 subjects |
| Placebo Group | Number of Subjects Reporting Rotavirus Gastroenteritis Episode(s) | 0 subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: Throughout the study period (2-3 months).
Population: Analysis was performed on the Total Vaccinated Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 17 subjects |
| Placebo Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 13 subjects |
Secondary
Number of Subjects Reporting Solicited Symptoms
Solicited symptoms assessed include cough, diarrhoea, irritability, loss of appetite , fever and vomiting.
Time frame: During the 8-day (Day 0 - Day 7) follow-up period after each vaccine dose.
Population: Analysis was performed on the Total Vaccinated Cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Cough | 180 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Diarrhoea | 20 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Irritability | 290 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Loss of appetite | 174 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Fever | 67 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Vomiting | 95 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Fever | 18 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Cough | 66 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Loss of appetite | 60 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Diarrhoea | 7 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Vomiting | 36 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Irritability | 106 subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Unsolicited AE covers any AE 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.
Time frame: During the 31-day (Day 0 - Day 30) follow-up period after each vaccine dose
Population: Analysis was performed on the Total Vaccinated Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 148 subjects |
| Placebo Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 59 subjects |
Secondary
Serum Anti-rotavirus Immunoglobulin A Antibody Concentrations
Concentrations are given as Geometric Mean Concentrations (GMCs). Note: In the Placebo Group the value was below the assay cut-off (20 units per milliliter).
Time frame: One month after the second vaccine dose
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, on subjects with available results.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Rotarix Group | Serum Anti-rotavirus Immunoglobulin A Antibody Concentrations | 208.5 units per milliliter (U/mL) |
| Placebo Group | Serum Anti-rotavirus Immunoglobulin A Antibody Concentrations | NA units per milliliter (U/mL) |