Infections, Rotavirus
Conditions
Keywords
HRV, Lyophilized formulation, Liquid formulation, Human rotavirus vaccine, Rotarix, Healthy infants, PCV-free, Porcine circovirus-free
Brief summary
The purpose of this study is to complete the total safety database size for GlaxoSmithKline Biologicals' (GSK's) human rotavirus (HRV) vaccine across the Porcine circovirus (PCV)-free development plan. This study used a purposely selected lot for PCV-free liquid HRV vaccine that is in the upper range of the usual release potencies. The PCV-free liquid HRV vaccine lots used were stored frozen in order to keep the titer stable until administration during the study. As the liquid formulation of GSK's HRV vaccine is not licensed in the US, the lyophilized formulation of the vaccine was used as a control in all phase III studies as part of the PCV-free development plan.
Interventions
BIOLOGICALPCV-free liquid formulation of GSK's oral live attenuated HRV vaccine
2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.
BIOLOGICALLyophilized formulation of GSK's oral live attenuated HRV vaccine
2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Data were collected in an observer-blind manner. By observer-blind, it is meant that during the study period, the vaccine(s) recipient and those responsible for the evaluation of any study endpoint (e.g. safety and reactogenicity) were all unaware of which vaccine was administered.
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
All subjects must satisfy all the following criteria at study entry: * Subjects' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). * Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure. * Healthy subjects as established by medical history and clinical examination before entering into the study. * A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.
Exclusion criteria
Medical conditions * Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for Intussusception (IS). * Very prematurely born infants (born ≤28 weeks of gestation). * History of IS. * Family history of congenital or hereditary immunodeficiency. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * Hypersensitivity to latex. * Major congenital defects or serious chronic illness, as assessed by the investigator. * Previous confirmed occurrence of Rotavirus Gastroenteritis (RV GE). * History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. * History of Severe combined immunodeficiency (SCID). Prior/Concomitant therapy * Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 1), or planned use during the study period. * Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study, and other licensed routine childhood vaccinations. * Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). * Administration of immunoglobulins and/or any blood products from birth or planned administration during the study period. * Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone ≥0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. * Previous vaccination against RV. Prior/Concurrent clinical study experience * 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 vaccine/product (drug or medical device). Other exclusions • Child in care.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | During the 8-day follow-up period after the first vaccination (vaccines administered at Day 1) | Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination. |
| Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | During the 8-day follow-up period after the second vaccination (vaccines administered at Month 1 or Month 2) | Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination. |
| Number of Subjects With Any Unsolicited AEs | During the 31-day follow-up period across doses (vaccines administered at Day 1 and at Month 1 or Month 2) | An unsolicited AE is defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment, and reported in addition to those solicited during the clinical study and any 'solicited' AE with onset outside the specified period of follow-up for solicited symptoms. Any = occurrence of AE regardless of intensity grade or relation to study vaccination. |
| Number of Subjects With Any Serious Adverse Events (SAEs) | Throughout the study period (from Day 1 up to Month 7 or Month 8) | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any = occurrence of SAE regardless of intensity grade or relation to study vaccination. |
Countries
Canada, Hong Kong, Taiwan, Turkey (Türkiye), United States
Participant flow
Recruitment details
The study was conducted in 5 countries/regions (Canada, Hong Kong, Taiwan, Turkey and United States).
Pre-assignment details
All 1351 participants enrolled in the study, received a study vaccination and were included in the Exposed Set.
Participants by arm
| Arm | Count |
|---|---|
| HRV PCV-free Liq Group Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) porcine circovirus (PCV)-free vaccine in liquid formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries. PCV-free implies no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. | 677 |
| HRV Lyo Group Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in lyophilized formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries. | 674 |
| Total | 1,351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | CONSENT WITHDRAWAL NOT DUE TO ADV. EVENT | 13 | 12 |
| Overall Study | Lost to Follow-up | 6 | 4 |
| Overall Study | MIGRATED / MOVED FROM THE STUDY AREA | 3 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | HRV Lyo Group | Total | HRV PCV-free Liq Group |
|---|---|---|---|
| Age, Continuous | 9.0 Weeks STANDARD_DEVIATION 1.5 | 9.0 Weeks STANDARD_DEVIATION 1.5 | 9.0 Weeks STANDARD_DEVIATION 1.5 |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 301 Participants | 603 Participants | 302 Participants |
| Race/Ethnicity, Customized Black Or African American | 10 Participants | 24 Participants | 14 Participants |
| Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other, Not specified | 14 Participants | 34 Participants | 20 Participants |
| Race/Ethnicity, Customized White | 346 Participants | 685 Participants | 339 Participants |
| Sex: Female, Male Female | 357 Participants | 693 Participants | 336 Participants |
| Sex: Female, Male Male | 317 Participants | 658 Participants | 341 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 677 | 0 / 674 |
| other Total, other adverse events | 591 / 677 | 571 / 674 |
| serious Total, serious adverse events | 39 / 677 | 38 / 674 |
Outcome results
Primary
Number of Subjects With Any Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any = occurrence of SAE regardless of intensity grade or relation to study vaccination.
Time frame: Throughout the study period (from Day 1 up to Month 7 or Month 8)
Population: Analysis was performed on the Exposed set (ES), which included all subjects with at least one study vaccine administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV PCV-free Liq Group | Number of Subjects With Any Serious Adverse Events (SAEs) | 39 Participants |
| HRV Lyo Group | Number of Subjects With Any Serious Adverse Events (SAEs) | 38 Participants |
Primary
Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination
Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination.
Time frame: During the 8-day follow-up period after the first vaccination (vaccines administered at Day 1)
Population: Analysis was performed on the Exposed set (ES), which included all subjects with at least one study vaccine administration documented and with the diary card completed after the first vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Cough / Runny Nose, Any | 139 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Diarrhea, Any | 41 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Fever, ≥ 38.0°C | 27 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Irritability / Fussiness, Any | 431 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Loss of appetite, Any | 201 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Vomiting, Any | 113 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Loss of appetite, Any | 186 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Cough / Runny Nose, Any | 166 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Irritability / Fussiness, Any | 428 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Diarrhea, Any | 47 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Vomiting, Any | 122 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Fever, ≥ 38.0°C | 21 Participants |
Primary
Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination
Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination.
Time frame: During the 8-day follow-up period after the second vaccination (vaccines administered at Month 1 or Month 2)
Population: Analysis was performed on the Exposed set (ES), which included all subjects with at least one study vaccine administration documented and with the diary card completed after the second vaccination.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Cough / Runny Nose, Any | 147 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Diarrhea, Any | 28 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Fever, ≥ 38.0°C | 46 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Irritability / Fussiness, Any | 368 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Loss of appetite, Any | 170 Participants |
| HRV PCV-free Liq Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Vomiting, Any | 82 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Loss of appetite, Any | 168 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Cough / Runny Nose, Any | 145 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Irritability / Fussiness, Any | 362 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Diarrhea, Any | 36 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Vomiting, Any | 88 Participants |
| HRV Lyo Group | Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Fever, ≥ 38.0°C | 40 Participants |
Primary
Number of Subjects With Any Unsolicited AEs
An unsolicited AE is defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment, and reported in addition to those solicited during the clinical study and any 'solicited' AE with onset outside the specified period of follow-up for solicited symptoms. Any = occurrence of AE regardless of intensity grade or relation to study vaccination.
Time frame: During the 31-day follow-up period across doses (vaccines administered at Day 1 and at Month 1 or Month 2)
Population: Analysis was performed on the Exposed set (ES), which included all subjects with at least one study vaccine administration documented.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HRV PCV-free Liq Group | Number of Subjects With Any Unsolicited AEs | 201 Participants |
| HRV Lyo Group | Number of Subjects With Any Unsolicited AEs | 206 Participants |