Infections, Rotavirus
Conditions
Keywords
Intussusception, Gastroenteritis, Finland
Brief summary
To assess the long-term efficacy and safety of the subjects during the third year after priming with 2 doses of GSK Biologicals' oral live attenuated HRV vaccine (Rotarix) in the primary vaccination study (102247). The Rotarix vaccine was administered in the primary vaccination study. There was no vaccine/intervention in this long-term efficacy study.
Interventions
BIOLOGICALRotarix (primary vaccination study)
GlaxoSmithKline Biologicals' oral live attenuated human rotavirus vaccine.
BIOLOGICALPlacebo (primary vaccination study)
Two liquid oral doses of placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
32 Months to 3 Years
Healthy volunteers
Yes
Inclusion criteria
* A male or female who has completed the second year efficacy follow-up of the primary vaccination study in Finland. * Written informed consent obtained from the parent or guardian of the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) | During the study period for the long-term follow-up (i.e. 6 months) | Occurence of any rotavirus gastroenteritis (RVGE) caused by the circulating wild-type rotavirus strain was assessed in terms of number of subjects experiencing diarrhoea with or without vomiting. Two occurrences of diarrhoea were classified as separate episodes if there were 5 or more diarrhoea-free days between the episodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With G1 Serotype | During the study period for the long-term follow-up (i.e. 6 months) | Occurence of any rotavirus gastroenteritis (RVGE) caused by the circulating wild-type rotavirus strain was assessed in terms of number of subjects experiencing diarrhoea with or without vomiting. Two occurrences of diarrhoea were classified as separate episodes if there were 5 or more diarrhoea-free days between the episodes. Only GE episodes in which wild-type RV strain of G1 serotype was identified in a stool specimen, were included in the efficacy analysis. |
| Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With G1 Serotype | During the study period for the long-term follow-up (i.e. 6 months) | Number of rotavirus gastroenteritis (RVGE) episodes caused by the wild-type rotavirus strain of serotype G1 and reported during the efficacy period, were presented by severity, using the Vesikari scale. The assessment of intensity of GE episodes was done using the 20-point Vesikari scale, according to which episodes with scores greater than or equal to (≥) 11 were labeled as severe. |
| Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype | During the study period for the long-term follow-up (i.e. 6 months) | Occurence of any rotavirus gastroenteritis (RVGE) caused by the circulating wild-type rotavirus strain of non-G1 serotype was assessed in terms of number of subjects experiencing diarrhoea with or without vomiting. Two occurrences of diarrhoea were classified as separate episodes if there were 5 or more diarrhoea-free days between the episodes. |
| Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) | During the study period for the long-term follow-up (i.e. 6 months) | Number of rotavirus gastroenteritis (RVGE) episodes caused by the wild-type rotavirus strain and reported during the efficacy period, were presented by severity, using the Vesikari scale. The assessment of intensity of GE episodes was done using the 20-point Vesikari scale, according to which episodes with scores greater than or equal to (≥) 11 were labeled as severe. |
| Number of Subjects With Severe Gastroenteritis (GE) | During the study period for the long-term follow-up (i.e. 6 months) | Severe GE was defined as a GE episode requiring hospitalization and/or re-hydration therapy in a medical facility. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | During the study period for the long-term follow-up (i.e. 6 months) | An SAE was any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. |
| Number of Subjects Reporting Intussusception (IS) | During the period starting from the end of the second follow-up up to the start of the study (up to 6 months) | Intussusception is defined as the telescoping of the intestine. |
| Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype | During the study period for the long-term follow-up (i.e. 6 months) | Number of rotavirus gastroenteritis (RVGE) episodes caused by the wild-type rotavirus strain of non-G1 serotype and reported during the efficacy period, were presented by severity, using the Vesikari scale. The assessment of intensity of GE episodes was done using the 20-point Vesikari scale, according to which episodes with scores greater than or equal to (≥) 11 were labeled as severe. |
Countries
Finland
Participant flow
Pre-assignment details
During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.
Participants by arm
| Arm | Count |
|---|---|
| Rotarix Group Healthy children between and including 6 to 12 weeks of age at the time of first vaccination, who received two powdered oral doses of Rotarix™ vaccine in the Rota-036 primary vaccination study (102247), were subsequently followed-up for 6 months during their third year of age, in scope of the present study. | 1,082 |
| Placebo Group Healthy children between and including 6 to 12 weeks of age at the time of first vaccination, who received two liquid oral doses of placebo in the Rota-036 primary vaccination study (102247), were subsequently followed-up for 6 months during their third year of age, in scope of the present study. | 531 |
| Total | 1,613 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 12 | 8 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Rotarix Group | Placebo Group | Total |
|---|---|---|---|
| Age, Continuous | 31.2 Months STANDARD_DEVIATION 1.12 | 31.3 Months STANDARD_DEVIATION 1.19 | 31.23 Months STANDARD_DEVIATION 1.14 |
| Sex: Female, Male Female | 510 Participants | 266 Participants | 776 Participants |
| Sex: Female, Male Male | 572 Participants | 265 Participants | 837 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1,082 | 0 / 531 |
| serious Total, serious adverse events | 4 / 1,082 | 7 / 531 |
Outcome results
Primary
Number of Subjects With Any Rotavirus Gastroenteritis (RVGE)
Occurence of any rotavirus gastroenteritis (RVGE) caused by the circulating wild-type rotavirus strain was assessed in terms of number of subjects experiencing diarrhoea with or without vomiting. Two occurrences of diarrhoea were classified as separate episodes if there were 5 or more diarrhoea-free days between the episodes.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all subjects from the ATP efficacy cohort of the primary study (102247) who entered into the efficacy surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) | 4 Subjects |
| Placebo Group | Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) | 3 Subjects |
Comparison: Vaccine efficacy with respect to any rotavirus gastroenteritis (RV GE) caused by the circulating wild-type rotavirus strain. Vaccine efficacy (VE) was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.p-value: 0.69195% CI: [-348.7, 88.9]Fisher Exact
Secondary
Number of Subjects Reporting Intussusception (IS)
Intussusception is defined as the telescoping of the intestine.
Time frame: During the period starting from the end of the second follow-up up to the start of the study (up to 6 months)
Population: The analysis was performed on the Total Cohort, which included all subjects who participated in this follow up study with at least one vaccine administration documented in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Intussusception (IS) | 0 Subjects |
| Placebo Group | Number of Subjects Reporting Intussusception (IS) | 0 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
An SAE was any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the Total Cohort, which included all subjects who participated in this follow up study with at least one vaccine administration documented in the primary study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 4 Subjects |
| Placebo Group | Number of Subjects Reporting Serious Adverse Events (SAEs) | 7 Subjects |
Secondary
Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With G1 Serotype
Occurence of any rotavirus gastroenteritis (RVGE) caused by the circulating wild-type rotavirus strain was assessed in terms of number of subjects experiencing diarrhoea with or without vomiting. Two occurrences of diarrhoea were classified as separate episodes if there were 5 or more diarrhoea-free days between the episodes. Only GE episodes in which wild-type RV strain of G1 serotype was identified in a stool specimen, were included in the efficacy analysis.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all subjects from the ATP efficacy cohort of the primary study (102247) who entered into the efficacy surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With G1 Serotype | 0 Subjects |
| Placebo Group | Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With G1 Serotype | 2 Subjects |
Secondary
Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype
Occurence of any rotavirus gastroenteritis (RVGE) caused by the circulating wild-type rotavirus strain of non-G1 serotype was assessed in terms of number of subjects experiencing diarrhoea with or without vomiting. Two occurrences of diarrhoea were classified as separate episodes if there were 5 or more diarrhoea-free days between the episodes.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all subjects from the ATP efficacy cohort of the primary study (102247) who entered into the efficacy surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype | 4 Subjects |
| Placebo Group | Number of Subjects With Any Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype | 1 Subjects |
Comparison: Vaccine efficacy with respect to any rotavirus gastroenteritis (RVGE) caused by the wild-type rotavirus strain of non-G1 serotype. Vaccine efficacy (VE) was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.p-value: 195% CI: [-9610.8, 80.5]Fisher Exact
Secondary
Number of Subjects With Severe Gastroenteritis (GE)
Severe GE was defined as a GE episode requiring hospitalization and/or re-hydration therapy in a medical facility.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all subjects from the ATP efficacy cohort of the primary study (102247) who entered into the efficacy surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects With Severe Gastroenteritis (GE) | 15 Subjects |
| Placebo Group | Number of Subjects With Severe Gastroenteritis (GE) | 6 Subjects |
Comparison: Vaccine efficacy with respect to severe gastroenteritis (GE) was assessed. Vaccine efficacy (VE) was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.p-value: 0.81795% CI: [-287.7, 54.8]Fisher Exact
Secondary
Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE)
Number of rotavirus gastroenteritis (RVGE) episodes caused by the wild-type rotavirus strain and reported during the efficacy period, were presented by severity, using the Vesikari scale. The assessment of intensity of GE episodes was done using the 20-point Vesikari scale, according to which episodes with scores greater than or equal to (≥) 11 were labeled as severe.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all subjects from the ATP efficacy cohort of the primary study (102247) who entered into the efficacy surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) | 1 Subjects |
| Placebo Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) | 1 Subjects |
Comparison: Vaccine efficacy with respect to severe rotavirus gastroenteritis (RVGE) caused by the circulating wild-type rotavirus strain was assessed. Vaccine efficacy (VE) was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who have received placebo.p-value: 0.55195% CI: [-3769.6, 99.4]Fisher Exact
Secondary
Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With G1 Serotype
Number of rotavirus gastroenteritis (RVGE) episodes caused by the wild-type rotavirus strain of serotype G1 and reported during the efficacy period, were presented by severity, using the Vesikari scale. The assessment of intensity of GE episodes was done using the 20-point Vesikari scale, according to which episodes with scores greater than or equal to (≥) 11 were labeled as severe.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all subjects from the ATP efficacy cohort of the primary study (102247) who entered into the efficacy surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With G1 Serotype | 0 Subjects |
| Placebo Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With G1 Serotype | 1 Subjects |
Comparison: Vaccine efficacy with respect to severe rotavirus gastroenteritis (RVGE) caused by the wild-type rotavirus strain of serotype G1. Vaccine efficacy (VE) was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.p-value: 0.3395% CI: [-1822.5, 100]Fisher Exact
Secondary
Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype
Number of rotavirus gastroenteritis (RVGE) episodes caused by the wild-type rotavirus strain of non-G1 serotype and reported during the efficacy period, were presented by severity, using the Vesikari scale. The assessment of intensity of GE episodes was done using the 20-point Vesikari scale, according to which episodes with scores greater than or equal to (≥) 11 were labeled as severe.
Time frame: During the study period for the long-term follow-up (i.e. 6 months)
Population: The analysis was performed on the According-to-Protocol (ATP) cohort for efficacy, which included all subjects from the ATP efficacy cohort of the primary study (102247) who entered into the efficacy surveillance period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype | 1 Subjects |
| Placebo Group | Number of Subjects With Severe Rotavirus Gastroenteritis (RVGE) With Non-G1 Serotype | 0 Subjects |
Comparison: Vaccine efficacy with respect to severe rotavirus gastroenteritis (RVGE) caused by the wild-type rotavirus strain of non-G1 serotype was assessed. Vaccine efficacy (VE) was defined as the percent reduction in the frequency of the relevant outcome variable in vaccinated subjects compared with those subjects who received placebo.p-value: 195% CI: [0, 98.7]Fisher Exact