Infections, Rotavirus, Rotavirus Vaccines
Conditions
Keywords
safety, Post-marketing surveillance (PMS), Rotarix, oral, Filipino, Rotavirus, Gastroenteritis, Human Rotavirus (HRV) vaccine
Brief summary
GSK has submitted a registration file for its live attenuated oral human rotavirus (HRV) vaccine in several countries. In view of its registration in the Philippines, the present study will collect data on the safety of the vaccine in the local target population as per the Bureau of Food and Drugs Directive.
Detailed description
The protocol was amended to reflect a change in the prescribing information. The age of the infants was changed from 6 - 14 weeks to at least 6 weeks at the time of the first vaccination. This protocol posting has been amended in order to comply with FDA AA.
Interventions
BIOLOGICALRotarix
Two doses of the oral vaccine
OTHERData collection
Safety evaluation: recording of adverse events by using diary cards and by non-leading questioning.
Sponsors
GlaxoSmithKline
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 24 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 (e.g. completion of the diary cards, return for follow-up visits) should be enrolled in the study. * A Filipino male or female aged at least 6 weeks at the time of the first vaccination. * Written informed consent obtained from the parent or guardian of the subject.
Exclusion criteria
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Any history of chronic gastrointestinal disease including any uncorrected congenital malformation of the GI tract. * Any contraindications as stated in the Prescribing Information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Grade 2 or 3 Symptoms (Fever, Vomiting or Diarrhea). | During the 15-day (Days 0-14) solicited follow-up period after each vaccine dose (Dose 1 and Dose 2). | Grade 2 or 3 symptoms assessed include fever, vomiting and diarrhea. Grade 2 fever was defined as axillary temperature above 38.0 degrees Celsius (°C) and below or equal to 39.0°C or rectal temperature above 38.5°C and below or equal to 39.5°C. Grade 3 fever was defined as axillary temperature above 39.0°C. Grade 2 vomiting was defined as 2 episodes of vomiting per day. Grade 3 vomiting was defined as at least 3 episodes of vomiting per day. Grade 2 diarrhea was defined as 4-5 looser than normal stools per day. Grade 3 diarrhea was defined as at least 6 looser than normal stools per day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | During the 15-day solicited follow-up period (Day 0 to Day 14) after each vaccine dose (Dose 1 and Dose 2). | Solicited symptoms assessed included cough, diarrhea, fever, irritability, loss of appetite and vomiting. Any = Any reports of the specified symptom irrespective of intensity grade and relationship to vaccination. Grade 3 symptom: symptom that prevented normal activity. Grade 3 loss of appetite = not eating at all, grade 3 fever = axillary temperature \> 39.0°C, grade 3 vomiting = ≥ 3 episodes of vomiting/day and grade 3 diarrhea = ≥ 6 looser than normal stools/day. Related = symptom assessed by the investigator as causally related to the vaccination regardless of intensity grade. |
| Number of Subjects Reporting Unsolicited Adverse Events (AE) | During the 31-day follow-up period (Day 0 to Day 30) after any vaccine dose. | An unsolicited AE covers 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. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. |
| Number of Subjects Reporting Serious Adverse Events (SAE) | Throughout the study period (Day 0 to one month post-Dose 2). | Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. |
Countries
Philippines
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rotarix Group Subjects received 2 doses of Rotarix administered at an interval of not less than 4 weeks between the doses. The first dose was administered at the age of 6 weeks and the vaccination course completed by the age of 24 weeks. | 1,439 |
| Total | 1,439 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Lost to Follow-up | 92 |
| Overall Study | Other | 19 |
| Overall Study | Protocol Violation | 12 |
| Overall Study | Withdrawal by Subject | 12 |
Baseline characteristics
| Characteristic | Rotarix Group |
|---|---|
| Age, Continuous | 11.2 Weeks STANDARD_DEVIATION 3.88 |
| Sex: Female, Male Female | 692 Participants |
| Sex: Female, Male Male | 747 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1,439 |
| other Total, other adverse events | 827 / 1,439 |
| serious Total, serious adverse events | 33 / 1,439 |
Outcome results
Primary
Number of Subjects Reporting Grade 2 or 3 Symptoms (Fever, Vomiting or Diarrhea).
Grade 2 or 3 symptoms assessed include fever, vomiting and diarrhea. Grade 2 fever was defined as axillary temperature above 38.0 degrees Celsius (°C) and below or equal to 39.0°C or rectal temperature above 38.5°C and below or equal to 39.5°C. Grade 3 fever was defined as axillary temperature above 39.0°C. Grade 2 vomiting was defined as 2 episodes of vomiting per day. Grade 3 vomiting was defined as at least 3 episodes of vomiting per day. Grade 2 diarrhea was defined as 4-5 looser than normal stools per day. Grade 3 diarrhea was defined as at least 6 looser than normal stools per day.
Time frame: During the 15-day (Days 0-14) solicited follow-up period after each vaccine dose (Dose 1 and Dose 2).
Population: The analysis was performed on the Total Vaccinated cohort which included all vaccinated subjects with at least one dose of the Rotarix vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Group | Number of Subjects Reporting Grade 2 or 3 Symptoms (Fever, Vomiting or Diarrhea). | Grade 2/3;Dose 1 | 147 Subjects |
| Rotarix Group | Number of Subjects Reporting Grade 2 or 3 Symptoms (Fever, Vomiting or Diarrhea). | Grade 2/3; Dose 2 | 98 Subjects |
| Rotarix Group | Number of Subjects Reporting Grade 2 or 3 Symptoms (Fever, Vomiting or Diarrhea). | Grade 2/3; Across Doses | 212 Subjects |
Secondary
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
Solicited symptoms assessed included cough, diarrhea, fever, irritability, loss of appetite and vomiting. Any = Any reports of the specified symptom irrespective of intensity grade and relationship to vaccination. Grade 3 symptom: symptom that prevented normal activity. Grade 3 loss of appetite = not eating at all, grade 3 fever = axillary temperature \> 39.0°C, grade 3 vomiting = ≥ 3 episodes of vomiting/day and grade 3 diarrhea = ≥ 6 looser than normal stools/day. Related = symptom assessed by the investigator as causally related to the vaccination regardless of intensity grade.
Time frame: During the 15-day solicited follow-up period (Day 0 to Day 14) after each vaccine dose (Dose 1 and Dose 2).
Population: The analysis was performed on the Total Vaccinated cohort , which included all vaccinated subjects with at least one dose of the Rotarix vaccine administration documented.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Cough; Dose 1 | 13 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Cough; Dose 1 | 15 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Diarrhea; Dose 1 | 69 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Diarrhea; Dose 1 | 13 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Diarrhea; Dose 1 | 26 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 1 | 130 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 1 | 3 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Irritability; Dose 1 | 100 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Loss of appetite; Dose 1 | 269 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Vomiting; Dose 1 | 44 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Vomiting; Dose 1 | 38 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Cough; Dose 2 | 256 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Cough; Dose 2 | 7 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Loss of appetite; Dose 2 | 193 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Loss of appetite; Dose 2 | 5 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Loss of appetite; Dose 2 | 43 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Cough; Across Doses | 39 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Diarrhea; Across Doses | 93 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Diarrhea; Across Doses | 18 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Diarrhea; Across Doses | 36 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Across Doses | 7 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Across Doses | 48 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Irritability; Across Doses | 545 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Irritability; Across Doses | 51 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Irritability; Across Doses | 130 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Loss of appetite; Across Doses | 351 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Loss of appetite; Across Doses | 8 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Loss of appetite; Across Doses | 93 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Vomiting; Across Doses | 240 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Vomiting; Across Doses | 54 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Vomiting; Across Doses | 49 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Cough; Dose 1 | 311 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 1 | 26 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Irritability; Dose 1 | 464 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Irritability; Dose 1 | 36 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Loss of appetite; Dose 1 | 4 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Loss of appetite; Dose 1 | 74 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Vomiting; Dose 1 | 190 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Cough; Dose 2 | 27 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Diarrhea; Dose 2 | 38 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Diarrhea; Dose 2 | 5 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Diarrhea; Dose 2 | 14 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Dose 2 | 130 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Temperature; Dose 2 | 4 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Temperature; Dose 2 | 24 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Irritability; Dose 2 | 307 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Irritability; Dose 2 | 24 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Irritability; Dose 2 | 71 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Vomiting; Dose 2 | 113 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Vomiting; Dose 2 | 13 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Related Vomiting; Dose 2 | 22 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Cough; Across Doses | 443 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Grade 3 Cough; Across Doses | 18 Subjects |
| Rotarix Group | Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms. | Any Temperature; Across Doses | 226 Subjects |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAE)
Serious adverse events (SAEs) assessed include medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject.
Time frame: Throughout the study period (Day 0 to one month post-Dose 2).
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one dose of the Rotarix vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Serious Adverse Events (SAE) | 33 Participants |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events (AE)
An unsolicited AE covers 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. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.
Time frame: During the 31-day follow-up period (Day 0 to Day 30) after any vaccine dose.
Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects with at least one dose of the Rotarix vaccine administration documented.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotarix Group | Number of Subjects Reporting Unsolicited Adverse Events (AE) | 352 Subjects |