Infections, Rotavirus
Conditions
Keywords
Rotavirus gastroenteritis, HRV vaccine
Brief summary
The primary objective of this study is to determine if the GSK Biologicals' human rotavirus (HRV) vaccine (pooled HRV groups) given concomitantly with routine expanded program on immunisation (EPI) vaccinations can prevent severe rotavirus gastroenteritis (≥11 on the 20-point Vesikari scoring system \[Ruuska, 1990\]) caused by the circulating wild-type RV strains during the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 5. The primary objective will be reached if the lower limit of the 95% confidence interval (CI) on vaccine efficacy is \>0%. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Detailed description
The study will have three groups: Rotarix 3-Dose Group, Rotarix 2-Dose Group and Placebo Group. Three-dose immunisation will be administered in healthy infants at approximately 6, 10, and 14 weeks of age. Routine EPI vaccinations will be administered concomitantly with the study vaccines. This study will also evaluate immunogenicity and safety relative to the placebo.
Interventions
BIOLOGICALRotarix™
Two or Three doses, oral administration
BIOLOGICALPlacebo
One or three doses, 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
5 Weeks to 10 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 child between, and including, 5 and 10 weeks of age at the time of the first study vaccination. * Written informed consent obtained from the parent or guardian of the subject who is of legal age * Healthy subjects as established by medical history and clinical examination before entering into the study. * In South Africa, birth weight \> 2000 grams or if weight unknown, gestation period \> 36 weeks.
Exclusion criteria
* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. * 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 * Planned administration of a vaccine not foreseen by the study protocol within 14 days before each dose of study vaccine(s) and ending 14 days after. * Chronic administration (defined as more than 14 days) of immunosuppressants since birth. * History of use of experimental rotavirus vaccine. * Previous routine vaccination except Bacille Calmette-Guérin (BCG), hepatitis B virus (HBV) and oral poliovirus (OPV) vaccination at birth * Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator. * Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination * History of allergic disease or reaction likely to be exacerbated by any component of the vaccine. * Acute disease at the time of enrolment. * Gastroenteritis within 7 days preceding the first study vaccine administration * Previous confirmed occurrence of rotavirus gastroenteritis (RV GE). * A family history of congenital or hereditary immunodeficiency. * Administration of immunoglobulins and/or blood products since birth or planned administration during the study period. * History of any neurologic disorders or seizures. * Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | From 2 weeks after the last vaccine or placebo dose up to 1 year of age | Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | From 2 weeks after the last vaccine or placebo dose up to 1 year of age | Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample. |
| Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | From the first vaccine or placebo dose up to 1 year of age | Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. |
| In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | From 2 weeks after the third dose of vaccine or placebo up to 1 year of age | Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. |
| Number of Subjects Reporting Severe Gastroenteritis of Any Cause | From 2 weeks after the last vaccine or placebo dose up to 1 year of age | Number of subjects with gastroenteritis (three or more looser than normal stools or watery stools within a day) that scored ≥ 11 on the 20-point Vesikari scoring system. |
| Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | From 2 weeks after the last vaccine or placebo dose up to 1 year of age | RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin. |
| For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains | During the period from 2 weeks after the last dose of vaccine or placebo until study end | Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. |
| For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains | During the period from 2 weeks after the last dose of vaccine or placebo until study end | RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin. |
| Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | From 2 weeks after the last vaccine or placebo dose up to 1 year of age | Number of subjects presenting with three or more looser than normal stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1. |
| Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out | From the first dose of vaccine or placebo up to end of the study | An AE is 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. An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | From the first dose of vaccine or placebo up to end of the study | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. |
| Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects | One month after the last vaccine dose | An initially seronegative subject is a subject whose IgA antibody concentration was below the assay cut-off value of 20 Units per milliliter (U/mL) before administration of the first vaccine dose. |
| Number of Seroconverted Subjects | One month after the last vaccine or placebo dose | Seroconverted subjects are defined as subjects with appearance of anti-rotavirus IgA antibody concentration ≥ 20 U/mL in subjects initially (i.e. prior to the first dose of vaccine or placebo) seronegative for rotavirus. |
| Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies | One month after the last vaccine or placebo dose | Geometric mean concentrations are given as Units per milliliter (U/mL). |
| Number of Seropositive Subjects | One month after the last vaccine or placebo dose | Seropositive subjects are defined as subjects with anti-rotavirus IgA antibody concentration ≥ 20 U/mL. |
| For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | During the period from 2 weeks after the last dose of vaccine or placebo until study end | Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1. |
Countries
Malawi, South Africa
Participant flow
Recruitment details
Only subjects from Malawi and from Cohort 2 South Africa were asked to continue the study for a second follow-up period (Year 2).
Pre-assignment details
Of the total of 4941 subjects enrolled in this study, 2 subjects were allocated a subject number but did not get any study vaccine administered. Hence, only 4939 subjects were considered as 'started'. For the second follow-up period, as mentioned in the protocol the results are presented for Rotarix Pooled and Placebo Groups only.
Participants by arm
| Arm | Count |
|---|---|
| Rotarix 2-dose Group Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine). | 1,647 |
| Rotarix 3-dose Group Subjects received 3 doses of Rotarix™ (rotavirus vaccine). | 1,651 |
| Placebo Group Subjects received 3 doses of placebo. | 1,641 |
| Rotarix Pooled Group Subjects received 2 or 3 doses of Rotarix™ (rotavirus vaccine). | 3,298 |
| Total | 8,237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Efficacy Period (Year 1) | Adverse Event | 46 | 45 | 45 | 91 |
| First Efficacy Period (Year 1) | Lost to Follow-up | 116 | 142 | 116 | 258 |
| First Efficacy Period (Year 1) | Non-compliance | 2 | 1 | 2 | 3 |
| First Efficacy Period (Year 1) | Protocol Violation | 3 | 5 | 4 | 8 |
| First Efficacy Period (Year 1) | Return dates not reliable | 1 | 0 | 0 | 1 |
| First Efficacy Period (Year 1) | Subject's parent passed away | 0 | 1 | 0 | 1 |
| First Efficacy Period (Year 1) | Vaccinated at regular clinic | 0 | 0 | 1 | 0 |
| First Efficacy Period (Year 1) | Withdrawal by Subject | 59 | 74 | 81 | 133 |
| Second Efficacy Period (Year 2) | Adverse Event | 11 | 9 | 12 | 20 |
| Second Efficacy Period (Year 2) | Consenting parent passed away | 1 | 1 | 2 | 2 |
| Second Efficacy Period (Year 2) | Lost to Follow-up | 43 | 43 | 46 | 86 |
| Second Efficacy Period (Year 2) | Protocol Violation | 2 | 1 | 2 | 3 |
| Second Efficacy Period (Year 2) | Withdrawal by Subject | 4 | 3 | 2 | 7 |
Baseline characteristics
| Characteristic | Rotarix 2-dose Group | Rotarix 3-dose Group | Placebo Group | Rotarix Pooled Group | Total |
|---|---|---|---|---|---|
| Age, Continuous | 6.3 weeks STANDARD_DEVIATION 0.92 | 6.4 weeks STANDARD_DEVIATION 0.98 | 6.4 weeks STANDARD_DEVIATION 0.97 | 6.4 weeks STANDARD_DEVIATION 0.95 | 6.4 weeks STANDARD_DEVIATION 0.95 |
| Gender Female | 811 Participants | 839 Participants | 800 Participants | 1650 Participants | 4100 Participants |
| Gender Male | 836 Participants | 812 Participants | 841 Participants | 1648 Participants | 4137 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 1,647 | 0 / 1,651 | 0 / 3,298 | 0 / 1,641 |
| serious Total, serious adverse events | 222 / 1,647 | 199 / 1,651 | 421 / 3,298 | 246 / 1,641 |
Outcome results
Primary
Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Population: Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 30 subjects |
| Rotarix 3-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 26 subjects |
| Rotarix Pooled Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 56 subjects |
| Placebo Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 70 subjects |
Secondary
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains
RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin.
Time frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end
Population: The analysis was performed on the ATP cohort for efficacy of the combined efficacy follow-up periods.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains | 159 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains | 118 subjects |
Secondary
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains
RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin.
Time frame: During the period from 1 year of age to study end
Population: The analysis was performed on the ATP cohort for efficacy of the second efficacy period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains | 58 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains | 26 subjects |
Secondary
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1.
Time frame: During the period from 1 year of age to study end
Population: The analysis was performed on the ATP cohort for efficacy of the second efficacy period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | G1 WT | 10 subjects |
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | Non-G1 | 25 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | G1 WT | 11 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | Non-G1 | 10 subjects |
Secondary
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1.
Time frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end
Population: The analysis was performed on the ATP cohort for efficacy of the combined efficacy follow-up periods.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | G1 WT | 21 subjects |
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | Non-G1 | 60 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | G1 WT | 20 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type | Non-G1 | 48 subjects |
Secondary
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time frame: During the period from 1 year of age to study end
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for efficacy of the second efficacy period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains | 35 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains | 21 subjects |
Secondary
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end
Population: The analysis was performed on the According-To-Protocol (ATP) cohort for efficacy of the combined efficacy follow-up periods.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Pooled Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains | 81 subjects |
| Placebo Group | For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains | 66 subjects |
Secondary
Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies
Geometric mean concentrations are given as Units per milliliter (U/mL).
Time frame: One month after the last vaccine or placebo dose
Population: Analysis was performed on the ATP cohort for immunogenicity.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Rotarix 2-dose Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies | 72.5 U/mL |
| Rotarix 3-dose Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies | 67.9 U/mL |
| Rotarix Pooled Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies | 70.2 U/mL |
| Placebo Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies | 21.8 U/mL |
Secondary
Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects
An initially seronegative subject is a subject whose IgA antibody concentration was below the assay cut-off value of 20 Units per milliliter (U/mL) before administration of the first vaccine dose.
Time frame: One month after the last vaccine dose
Population: Analysis was performed on the ATP cohort for immunogenicity, only for initially seronegative subjects.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Rotarix 2-dose Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects | 56.6 Units per milliliter (U/mL) |
| Rotarix 3-dose Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects | 79.4 Units per milliliter (U/mL) |
| Rotarix Pooled Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects | 67.5 Units per milliliter (U/mL) |
| Placebo Group | Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects | 23.4 Units per milliliter (U/mL) |
Secondary
In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time frame: From 2 weeks after the third dose of vaccine or placebo up to 1 year of age
Population: Analysis was performed on the ATP cohort for efficacy, only for the subset of subjects in South Africa who were fully vaccinated before the beginning of the rotavirus season.~For this analysis, data from Rotarix 2-dose Group and Rotarix 3-dose Group were pooled into one group (Rotarix pooled Group).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 5 subjects |
| Rotarix 3-dose Group | In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 3 subjects |
| Rotarix Pooled Group | In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 8 subjects |
| Placebo Group | In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 20 subjects |
Secondary
Number of Seroconverted Subjects
Seroconverted subjects are defined as subjects with appearance of anti-rotavirus IgA antibody concentration ≥ 20 U/mL in subjects initially (i.e. prior to the first dose of vaccine or placebo) seronegative for rotavirus.
Time frame: One month after the last vaccine or placebo dose
Population: Analysis was performed on the ATP cohort for immunogenicity, only for inititally seronegative subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Seroconverted Subjects | 57 subjects |
| Rotarix 3-dose Group | Number of Seroconverted Subjects | 72 subjects |
| Rotarix Pooled Group | Number of Seroconverted Subjects | 129 subjects |
| Placebo Group | Number of Seroconverted Subjects | 25 subjects |
Secondary
Number of Seropositive Subjects
Seropositive subjects are defined as subjects with anti-rotavirus IgA antibody concentration ≥ 20 U/mL.
Time frame: One month after the last vaccine or placebo dose
Population: Analysis was performed on the ATP cohort for immunogenicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Seropositive Subjects | 756 subjects |
| Rotarix 3-dose Group | Number of Seropositive Subjects | 706 subjects |
| Rotarix Pooled Group | Number of Seropositive Subjects | 1462 subjects |
| Placebo Group | Number of Seropositive Subjects | 262 subjects |
Secondary
Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain
RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin.
Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Population: Analysis was performed on the ATP cohort for efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 78 subjects |
| Rotarix 3-dose Group | Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 64 subjects |
| Rotarix Pooled Group | Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 142 subjects |
| Placebo Group | Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain | 156 subjects |
Secondary
Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample.
Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Population: Analysis was performed on the ATP cohort for efficacy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 93 subjects |
| Rotarix 3-dose Group | Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 74 subjects |
| Rotarix Pooled Group | Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 167 subjects |
| Placebo Group | Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 174 subjects |
Secondary
Number of Subjects 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, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Time frame: From the first dose of vaccine or placebo up to end of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 222 subjects |
| Rotarix 3-dose Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 199 subjects |
| Rotarix Pooled Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 421 subjects |
| Placebo Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 246 subjects |
Secondary
Number of Subjects Reporting Severe Gastroenteritis of Any Cause
Number of subjects with gastroenteritis (three or more looser than normal stools or watery stools within a day) that scored ≥ 11 on the 20-point Vesikari scoring system.
Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Population: Analysis was performed on the ATP cohort for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Subjects Reporting Severe Gastroenteritis of Any Cause | 134 subjects |
| Rotarix 3-dose Group | Number of Subjects Reporting Severe Gastroenteritis of Any Cause | 122 subjects |
| Rotarix Pooled Group | Number of Subjects Reporting Severe Gastroenteritis of Any Cause | 256 subjects |
| Placebo Group | Number of Subjects Reporting Severe Gastroenteritis of Any Cause | 178 subjects |
Secondary
Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out
An AE is 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. An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
Time frame: From the first dose of vaccine or placebo up to end of the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out | 57 subjects |
| Rotarix 3-dose Group | Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out | 54 subjects |
| Rotarix Pooled Group | Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out | 111 subjects |
| Placebo Group | Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out | 56 subjects |
Secondary
Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain
Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time frame: From the first vaccine or placebo dose up to 1 year of age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix 2-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 37 subjects |
| Rotarix 3-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 31 subjects |
| Rotarix Pooled Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 68 subjects |
| Placebo Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain | 83 subjects |
Secondary
Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type
Number of subjects presenting with three or more looser than normal stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1.
Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Population: Analysis was performed on the ATP cohort for efficacy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix 2-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | Non-G1 | 22 subjects |
| Rotarix 2-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | G1 WT | 8 subjects |
| Rotarix 3-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | G1 WT | 9 subjects |
| Rotarix 3-dose Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | Non-G1 | 17 subjects |
| Rotarix Pooled Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | G1 WT | 17 subjects |
| Rotarix Pooled Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | Non-G1 | 39 subjects |
| Placebo Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | G1 WT | 23 subjects |
| Placebo Group | Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type | Non-G1 | 47 subjects |