Rotavirus Infections
Conditions
Keywords
Dose ranging, Neonatal vaccine, RV3-BB vaccine
Brief summary
The purpose of this study is to determine the serum IgA response of three dose levels of the oral RV3-BB vaccine when administered in a neonatal schedule or when administered as a high dose in an infant schedule.
Detailed description
The primary objective of this study is to assess the cumulative anti-rotavirus serum IgA response (defined as a ≥3 fold increase from baseline) 4 weeks after 3 doses of RV3-BB administered in a neonatal schedule at a High, Mid or low vaccine titre. In addition the cumulative anti-rotavirus serum IgA response (defined as a ≥3 fold increase from baseline) 4 weeks after 3 doses of RV3-BB administered in an infant schedule at a high dose of vaccine will be assessed along with cumulative vaccine take and components of vaccine take after 3 doses of RV3-BB administered in a neonatal or infant schedule. The safety and tolerability of RV3-BB when administered as an infant or as a neonatal schedule will be described.
Interventions
BIOLOGICALRV3-BB
Oral administration
BIOLOGICALPlacebo
Oral administration
Sponsors
Murdoch Childrens Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a Phase II, randomised, double-blind, placebo-controlled, four-arm parallel group study of two different dosing schedules of oral RV3-BB
Eligibility
Sex/Gender
ALL
Age
0 Days to 18 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Neonate is less than 6 days (≤144 hours) of age at the time of first dose. * Neonate is in good health as determined by clinical judgment, including a medical history and physical exam, which confirms the absence of a current or past disease state considered significant by the investigator. * Neonate birth weight 2500-4000g inclusive. * Neonate's parents/guardians expect to be available for the duration of the study, and agree to adhere to all protocol requirements. * Neonate's parents/guardians have provided written informed consent prior to study-related procedures being performed.
Exclusion criteria
* Any medical, psychiatric, or social condition of a parent/guardian that in the opinion of the investigator would prevent the neonate's parents/guardians from giving proper informed consent or from complying with the study protocol. * Neonates with known or suspected major congenital malformations or genetically determined disease. * Neonates with intussusception. * Neonates with a known or suspected bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. * Neonates who have ever received any blood products, including immunoglobulin, or for whom receipt of any blood product during the course of the study is anticipated. * Neonates in whom Essential Programme Immunisation (EPI) vaccines or components are contraindicated. * Neonates who have received or who expect to receive during the study period, any rotavirus vaccine other than those which will be administered as part of this study. * Neonates who have ever received, or who are anticipated to receive during the study period, any investigational agent other than those which will be administered as part of this study. * Neonates with a previous anaphylactic reaction to any drug, vaccine or vaccine component. * Neonates with a significant evolving neurological disorder. * Neonates whose parents/guardians are site team employees with direct involvement with the investigators, or who are working on the study. * Neonates who have been exposed to immunosuppressive courses of glucocorticosteroids, cytotoxic drugs or blood products through prenatal exposure and/or breast milk in the four weeks prior to randomization. * Neonates with diarrhoea or vomiting in the 24 hours preceding randomisation. * Neonates with any moderate or severe illness, and/or who have a temperature of ≥37.5˚C axillary/oral or ≥38˚C rectal/tympanic within the 48 hours preceding randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Cumulative Anti Rotavirus Serum Immunoglobulin A (IgA) Response (≥3 Fold Increase From Baseline) in Neonatal Vaccine Schedule at High Mid and Low Dose of RV3-BB | At serum collection at approximately 14 weeks of age | Cumulative anti rotavirus serum Immunoglobulin A (IgA) response is defined as a ≥3 fold increase from baseline at each serum collection time point to 4 weeks after 3 doses of RV3-BB |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule | At serum collection time points at approximately 14 and 18 weeks of age | Expressed as geometric mean titres (GMTs) from baseline to post dose 3 of RV3-BB Minimum 10 Maximum 250,000 Higher score considered to be immunogenic. |
| Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB. | Sample collections at Week 0 through to approximately 14 and 18 weeks of age | Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose |
| Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB | Sample collections at Week 0 through to approximately 14 and 18 weeks of age | Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational Product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose |
| Occurrence of Adverse Events (AE) | First dose of investigational product to Study End at approximately 18 weeks of age | Number of Participants with Adverse Events |
| Number of Participants With a Cumulative Anti Rotavirus Serum IgA Response (≥3 Fold Increase From Baseline) After 3 Doses in an Infant RV3-BB Schedule | At serum collection visit approximately 18 weeks of age | Defined as a ≥3 fold increase from baseline to 4 weeks after 3 doses of RV3-BB at 18 weeks of age |
| Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Sample collections at Week 0 through to approximately 6 and 10 weeks of age | Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose |
| Occurrence of Serious Adverse Events (SAEs) | First dose of investigational product to Study End at approximately 18 weeks of age | Number of participants with Serious Adverse Events (SAEs) |
| Occurrence of Diarrhea. Severe | First dose of Investigational product to Study End at approximately 18 weeks of age | Diarrhea will be described according to severity and detection of wild type rotavirus in diarrhea samples collected. Severity defined using a modified version of the Vesikari clinical score for gastroenteritis. Severed is modified Vesikari score of greater than or equal to 11. The Vesikari scale is a 20-point scale based on duration and peak frequency of diarrhea and vomiting, degree of temperature, severity of dehydration, and treatment provided to the patient (i.e., rehydration or hospitalization). This scale is divided into three ranges: mild \<7, moderate 7-10, and severe ≥11 |
| Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Sample collections at Week 0 through to approximately 10 and 14 weeks of age | Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose |
Countries
Malawi
Participant flow
Recruitment details
A two-stage consent process was followed: * Pregnant women were invited to provide preliminary consent during the third trimester and prior to going into labour. * Post birth, the parents/guardians were invited to provide consent for their baby to participate in the study.
Participants by arm
| Arm | Count |
|---|---|
| High Dose RV3-BB Neonatal Schedule High dose neonatal RV3-BB vaccine schedule. RV3-BB Vaccine for Investigational product doses 1 (0-5 days), 2 (week 6) and 3 (week 10) and placebo for Investigational product dose 4 (week 14)
RV3-BB: Oral administration
Placebo: Oral administration | 178 |
| Mid Dose RV3-BB Neonatal Schedule Mid dose neonatal RV3-BB vaccine schedule. RV3-BB Vaccine for Investigational product doses 1 (0-5 days), 2 (week 6) and 3 (week 10) and placebo for Investigational product dose 4 (week 14)
RV3-BB: Oral administration
Placebo: Oral administration | 179 |
| Low Dose RV3-BB Neonatal Schedule Low dose neonatal RV3-BB vaccine schedule. RV3-BB Vaccine for Investigational product doses 1 (0-5 days), 2 (week 6) and 3 (week 10) and placebo for Investigational product dose 4 (week 14)
RV3-BB: Oral administration
Placebo: Oral administration | 175 |
| High Dose RV3-BB Infant Schedule High dose infant RV3-BB vaccine schedule. Placebo for Investigational product dose 1 (0-5 days) and RV3-BB Vaccine for Investigational product doses 2 (week 6) 3 (week 10) and dose 4 (week 14)
RV3-BB: Oral administration
Placebo: Oral administration | 179 |
| Total | 711 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 1 |
| Overall Study | Death | 1 | 0 | 2 | 1 |
| Overall Study | Lost to Follow-up | 9 | 4 | 9 | 5 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 7 |
| Overall Study | Unknown other reason | 3 | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 16 | 14 | 16 |
Baseline characteristics
| Characteristic | Mid Dose RV3-BB Neonatal Schedule | Low Dose RV3-BB Neonatal Schedule | High Dose RV3-BB Infant Schedule | High Dose RV3-BB Neonatal Schedule | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 179 Participants | 175 Participants | 179 Participants | 178 Participants | 711 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 1.4 Days STANDARD_DEVIATION 1.42 | 1.4 Days STANDARD_DEVIATION 1.45 | 1.5 Days STANDARD_DEVIATION 1.39 | 1.4 Days STANDARD_DEVIATION 1.5 | 1.5 Days STANDARD_DEVIATION 1.43 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 179 Participants | 175 Participants | 179 Participants | 178 Participants | 711 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Malawi | 179 Participants | 175 Participants | 179 Participants | 178 Participants | 711 Participants |
| Sex: Female, Male Female | 84 Participants | 88 Participants | 96 Participants | 101 Participants | 369 Participants |
| Sex: Female, Male Male | 95 Participants | 87 Participants | 83 Participants | 77 Participants | 342 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 | 1 / 170 | 0 / 172 | 2 / 169 | 1 / 173 |
| other Total, other adverse events | 67 / 170 | 68 / 172 | 69 / 169 | 59 / 173 |
| serious Total, serious adverse events | 11 / 170 | 7 / 172 | 8 / 169 | 5 / 173 |
Outcome results
Primary
Number of Participants With a Cumulative Anti Rotavirus Serum Immunoglobulin A (IgA) Response (≥3 Fold Increase From Baseline) in Neonatal Vaccine Schedule at High Mid and Low Dose of RV3-BB
Cumulative anti rotavirus serum Immunoglobulin A (IgA) response is defined as a ≥3 fold increase from baseline at each serum collection time point to 4 weeks after 3 doses of RV3-BB
Time frame: At serum collection at approximately 14 weeks of age
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Anti Rotavirus Serum Immunoglobulin A (IgA) Response (≥3 Fold Increase From Baseline) in Neonatal Vaccine Schedule at High Mid and Low Dose of RV3-BB | 79 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Anti Rotavirus Serum Immunoglobulin A (IgA) Response (≥3 Fold Increase From Baseline) in Neonatal Vaccine Schedule at High Mid and Low Dose of RV3-BB | 80 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Anti Rotavirus Serum Immunoglobulin A (IgA) Response (≥3 Fold Increase From Baseline) in Neonatal Vaccine Schedule at High Mid and Low Dose of RV3-BB | 57 participants |
95% CI: [0.039, 0.272]
95% CI: [-0.115, 0.117]
Comparison: Non-inferiority of the lower titre vaccine was demonstrated if the upper bound of the CI was below 20%95% CI: [0.038, 0.27]
Secondary
Number of Participants With a Cumulative Anti Rotavirus Serum IgA Response (≥3 Fold Increase From Baseline) After 3 Doses in an Infant RV3-BB Schedule
Defined as a ≥3 fold increase from baseline to 4 weeks after 3 doses of RV3-BB at 18 weeks of age
Time frame: At serum collection visit approximately 18 weeks of age
Population: Per protocol population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Anti Rotavirus Serum IgA Response (≥3 Fold Increase From Baseline) After 3 Doses in an Infant RV3-BB Schedule | 100 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Anti Rotavirus Serum IgA Response (≥3 Fold Increase From Baseline) After 3 Doses in an Infant RV3-BB Schedule | 96 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Anti Rotavirus Serum IgA Response (≥3 Fold Increase From Baseline) After 3 Doses in an Infant RV3-BB Schedule | 86 participants |
| High Dose RV3-BB Infant Schedule | Number of Participants With a Cumulative Anti Rotavirus Serum IgA Response (≥3 Fold Increase From Baseline) After 3 Doses in an Infant RV3-BB Schedule | 82 participants |
Secondary
Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB.
Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose
Time frame: Sample collections at Week 0 through to approximately 14 and 18 weeks of age
Population: Per protocol analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB. | Vaccine take | 118 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB. | Serum IgA | 79 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB. | Shedding RV3-BB vaccine virus | 85 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB. | Vaccine take | 120 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB. | Serum IgA | 82 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With a Cumulative Vaccine Take (Serum Anti Rotavirus IgA Response or Shedding of RV3-BB Vaccine Virus) and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High Dose of RV3-BB. | Shedding RV3-BB vaccine virus | 90 participants |
Secondary
Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB
Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose
Time frame: Sample collections at Week 0 through to approximately 6 and 10 weeks of age
Population: Per protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 51 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 29 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 31 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 45 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 15 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 31 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 12 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 23 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 12 participants |
| High Dose RV3-BB Infant Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 64 participants |
| High Dose RV3-BB Infant Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 48 participants |
| High Dose RV3-BB Infant Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 1 Dose of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 26 participants |
Secondary
Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB
Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose
Time frame: Sample collections at Week 0 through to approximately 10 and 14 weeks of age
Population: Per protocol population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 69 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 98 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 56 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 52 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 55 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 89 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 68 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 31 participants |
| Low Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 46 participants |
| High Dose RV3-BB Infant Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Vaccine take | 98 participants |
| High Dose RV3-BB Infant Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | RV3-BB vaccine shedding | 70 participants |
| High Dose RV3-BB Infant Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 2 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a High, Mid or Low Dose of RV3-BB | Serum IgA | 58 participants |
Secondary
Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB
Vaccine take is defined as at least a threefold increase in serum anti-rotavirus immunoglobulin A (IgA) from baseline to post Investigational Product dosing, or detectable RV3 shedding in stools (by ELISA or PCR) any day from day three to day five following administration of Investigational product. Cumulative vaccine take is defined as Vaccine take observed at the current assessment time point or following any previous dose
Time frame: Sample collections at Week 0 through to approximately 14 and 18 weeks of age
Population: Per protocol analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB | Vaccine take | 114 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB | Serum IgA | 80 participants |
| High Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB | RV3-BB Vaccine Shedding | 71 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB | Vaccine take | 94 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB | Serum IgA | 57 participants |
| Mid Dose RV3-BB Neonatal Schedule | Number of Participants With Cumulative Vaccine Take and Components of Vaccine Take After 3 Doses of RV3-BB Administered in a Neonatal or Infant Schedule at a Mid or Low Dose of RV3-BB | RV3-BB Vaccine Shedding | 62 participants |
Secondary
Occurrence of Adverse Events (AE)
Number of Participants with Adverse Events
Time frame: First dose of investigational product to Study End at approximately 18 weeks of age
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Occurrence of Adverse Events (AE) | 67 participants |
| Mid Dose RV3-BB Neonatal Schedule | Occurrence of Adverse Events (AE) | 68 participants |
| Low Dose RV3-BB Neonatal Schedule | Occurrence of Adverse Events (AE) | 69 participants |
| High Dose RV3-BB Infant Schedule | Occurrence of Adverse Events (AE) | 60 participants |
Secondary
Occurrence of Diarrhea. Severe
Diarrhea will be described according to severity and detection of wild type rotavirus in diarrhea samples collected. Severity defined using a modified version of the Vesikari clinical score for gastroenteritis. Severed is modified Vesikari score of greater than or equal to 11. The Vesikari scale is a 20-point scale based on duration and peak frequency of diarrhea and vomiting, degree of temperature, severity of dehydration, and treatment provided to the patient (i.e., rehydration or hospitalization). This scale is divided into three ranges: mild \<7, moderate 7-10, and severe ≥11
Time frame: First dose of Investigational product to Study End at approximately 18 weeks of age
Population: Full analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Occurrence of Diarrhea. Severe | 1 participants |
| Mid Dose RV3-BB Neonatal Schedule | Occurrence of Diarrhea. Severe | 2 participants |
| Low Dose RV3-BB Neonatal Schedule | Occurrence of Diarrhea. Severe | 2 participants |
| High Dose RV3-BB Infant Schedule | Occurrence of Diarrhea. Severe | 0 participants |
Secondary
Occurrence of Serious Adverse Events (SAEs)
Number of participants with Serious Adverse Events (SAEs)
Time frame: First dose of investigational product to Study End at approximately 18 weeks of age
Population: Safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Occurrence of Serious Adverse Events (SAEs) | 11 participants |
| Mid Dose RV3-BB Neonatal Schedule | Occurrence of Serious Adverse Events (SAEs) | 7 participants |
| Low Dose RV3-BB Neonatal Schedule | Occurrence of Serious Adverse Events (SAEs) | 8 participants |
| High Dose RV3-BB Infant Schedule | Occurrence of Serious Adverse Events (SAEs) | 5 participants |
Secondary
Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule
Expressed as geometric mean titres (GMTs) from baseline to post dose 3 of RV3-BB Minimum 10 Maximum 250,000 Higher score considered to be immunogenic.
Time frame: At serum collection time points at approximately 14 and 18 weeks of age
Population: Per protocol
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| High Dose RV3-BB Neonatal Schedule | Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule | 48.4 geometric mean titres | Standard Deviation 22339.87 |
| Mid Dose RV3-BB Neonatal Schedule | Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule | 39.9 geometric mean titres | Standard Deviation 21758.64 |
| Low Dose RV3-BB Neonatal Schedule | Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule | 28.0 geometric mean titres | Standard Deviation 7724.19 |
| High Dose RV3-BB Infant Schedule | Serum Anti Rotavirus IgA Titres in Participants Receiving RV3-BB in a Neonatal or Infant Schedule | 77.7 geometric mean titres | Standard Deviation 25020.69 |