Infections, Rotavirus, Rotavirus Vaccines
Conditions
Brief summary
This study is undertaken to provide the regulatory authorities in Japan with immunogenicity, efficacy, safety and reactogenicity data of GSK Biologicals' Human Rotavirus \[HRV\] vaccine, given as a 2-dose primary vaccination, in healthy Japanese infants aged approximately 2 months at the time of the first dose and previously uninfected with HRV. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
Combined diphtheria and tetanus toxoids and acellular pertussis (DTPa) and Hepatitis B (HBV) vaccines are allowed to be co-administered along with Rotarix vaccine/Placebo.
Interventions
BIOLOGICALRotarix
Two-dose oral vaccination.
BIOLOGICALPlacebo
Two-dose oral administration.
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 14 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female infant between, and including, 6 and 14 weeks (42-104 days) of age at the time of the first vaccination. * 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 * Healthy subjects as established by medical history and clinical examination before entering into the study. * Written informed consent obtained from the parent or guardian of the subject. * Born between a gestation period of 36 and 42 weeks inclusive.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the HRV vaccine within 30 days preceding the first dose of HRV vaccine, or planned use during the study period. * History of use of experimental rotavirus vaccine. * Chronic administration of immunosuppressants or other immune-modifying drugs since birth. * 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 (pharmaceutical product or device). * Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for intussusception. * Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract or other serious medical condition determined by the investigator. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Previous confirmed occurrence of RV GE. * Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required). * A family history of congenital or hereditary immunodeficiency. * Acute disease at the time of enrolment. * Gastroenteritis within 7 days preceding the study vaccine administration. * Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | From 2 weeks after Dose 2 up to 2 years of age | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type | From 2 weeks after Dose 2 up to 2 years of age | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe RV GE was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system). |
| Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types | From 2 weeks after Dose 2 up to 2 years of age | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system). |
| Number of Subjects Hospitalized Due to Rotavirus (RV) Gastroenteritis (GE) Caused by the Circulating Wild-type RV Strains | From 2 weeks after Dose 2 up to 2 years of age | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. |
| Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | From Dose 1 up to 2 years of age | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system). |
| Number of Subjects Reporting Severe Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | From 2 weeks after Dose 2 up to 2 years of age | A subject was considered as reporting severe rotavirus gastroenteritis when the subject scored 11 or more on a 20-point scoring system (Vesikari scoring system). |
| Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A (IgA) Antibodies | 2 months after Dose 2 | Seroconversion was defined as the appearance of anti-rotavirus immunoglobulin A antibody concentration ≥ 20 units (U)/milliliter (mL) in subjects initially (i.e. prior to the first dose of rotarix) seronegative. |
| Number of Subjects Reporting Solicited Symptoms | During the 8-day follow-up period after each dose | Solicited symptoms assessed include cough, diarrhoea, fever, irritability, loss of appetite and vomiting. |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | During the 31-day follow-up period after each dose | Unsolicited adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | Up to 2 years of age | Serious adverse events (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. |
| Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody Concentration | 2 months after Dose 2 | Anti-rotavirus immunoglobulin A antibody concentrations are given as geometric mean concentrations (GMCs). Arbitrary 'zero' values were set in the Placebo Group since the GMC was below the assay cut-off value (20 U/mL). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rotarix Group Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule. | 508 |
| Placebo Group Subjects received 2 oral doses of placebo according to a 0, 1 month schedule. | 257 |
| Total | 765 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 17 | 8 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Subject's mother pregnant | 0 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 5 |
Baseline characteristics
| Characteristic | Rotarix Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 7.7 weeks STANDARD_DEVIATION 1.99 | 7.7 weeks STANDARD_DEVIATION 2.05 | 7.7 weeks STANDARD_DEVIATION 2.01 |
| Sex: Female, Male Female | 229 Participants | 134 Participants | 363 Participants |
| Sex: Female, Male Male | 279 Participants | 123 Participants | 402 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 411 / 508 | 204 / 257 |
| serious Total, serious adverse events | 72 / 508 | 44 / 257 |
Outcome results
Primary
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode.
Time frame: From 2 weeks after Dose 2 up to 2 years of age
Population: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | 14 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | 34 subjects |
Secondary
Number of Subjects Hospitalized Due to Rotavirus (RV) Gastroenteritis (GE) Caused by the Circulating Wild-type RV Strains
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode.
Time frame: From 2 weeks after Dose 2 up to 2 years of age
Population: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Hospitalized Due to Rotavirus (RV) Gastroenteritis (GE) Caused by the Circulating Wild-type RV Strains | 1 subjects |
| Placebo Group | Number of Subjects Hospitalized Due to Rotavirus (RV) Gastroenteritis (GE) Caused by the Circulating Wild-type RV Strains | 2 subjects |
Secondary
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe RV GE was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system).
Time frame: From 2 weeks after Dose 2 up to 2 years of age
Population: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type | Any RV GE | 4 subjects |
| Rotarix Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type | Severe RV GE | 1 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type | Any RV GE | 13 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type | Severe RV GE | 6 subjects |
Secondary
Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system).
Time frame: From 2 weeks after Dose 2 up to 2 years of age
Population: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types | Any RV GE | 10 subjects |
| Rotarix Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types | Severe RV GE | 1 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types | Any RV GE | 21 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types | Severe RV GE | 6 subjects |
Secondary
Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains
Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system).
Time frame: From Dose 1 up to 2 years of age
Population: The analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Group | Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | Any RV GE | 14 subjects |
| Rotarix Group | Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | Severe RV GE | 2 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | Any RV GE | 36 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | Severe RV GE | 13 subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
Serious adverse events (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: Up to 2 years of age
Population: The analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 72 subjects |
| Placebo Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 44 subjects |
Secondary
Number of Subjects Reporting Severe Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains
A subject was considered as reporting severe rotavirus gastroenteritis when the subject scored 11 or more on a 20-point scoring system (Vesikari scoring system).
Time frame: From 2 weeks after Dose 2 up to 2 years of age
Population: The analysis was performed on the according-to-protocol (ATP) cohort for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Severe Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | 2 subjects |
| Placebo Group | Number of Subjects Reporting Severe Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | 12 subjects |
Secondary
Number of Subjects Reporting Solicited Symptoms
Solicited symptoms assessed include cough, diarrhoea, fever, irritability, loss of appetite and vomiting.
Time frame: During the 8-day follow-up period after each dose
Population: The analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Diarrhoea | 43 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Irritability | 261 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Cough | 184 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Loss of appetite | 81 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Fever | 62 subjects |
| Rotarix Group | Number of Subjects Reporting Solicited Symptoms | Vomiting | 74 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Vomiting | 36 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Cough | 92 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Diarrhoea | 14 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Fever | 22 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Irritability | 125 subjects |
| Placebo Group | Number of Subjects Reporting Solicited Symptoms | Loss of appetite | 33 subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Unsolicited adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: During the 31-day follow-up period after each dose
Population: The analysis was performed on the Total Vaccinated cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 279 subjects |
| Placebo Group | Number of Subjects Reporting Unsolicited Adverse Events (AEs) | 144 subjects |
Secondary
Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A (IgA) Antibodies
Seroconversion was defined as the appearance of anti-rotavirus immunoglobulin A antibody concentration ≥ 20 units (U)/milliliter (mL) in subjects initially (i.e. prior to the first dose of rotarix) seronegative.
Time frame: 2 months after Dose 2
Population: The analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A (IgA) Antibodies | 29 subjects |
| Placebo Group | Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A (IgA) Antibodies | 1 subjects |
Secondary
Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody Concentration
Anti-rotavirus immunoglobulin A antibody concentrations are given as geometric mean concentrations (GMCs). Arbitrary 'zero' values were set in the Placebo Group since the GMC was below the assay cut-off value (20 U/mL).
Time frame: 2 months after Dose 2
Population: The analysis was performed on the according-to-protocol (ATP) cohort for immunogenicity.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Rotarix Group | Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody Concentration | 217.0 Units per milliliter (U/mL) |
| Placebo Group | Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody Concentration | 0 Units per milliliter (U/mL) |