Evaluation of a Rotavirus Vaccine
Conditions
Brief summary
This is is a study of a parenteral rotavirus vaccine (P2-VP8 subunit rotavirus vaccine). The study will examine the safety and immunogenicity of this vaccine first in healthy South African toddlers. If the safety profile is deemed appropriate, the study will continue to explore the safety and immunogenicity of the vaccine in healthy South African infants. The primary safety hypothesis is that the P2-VP8 subunit rotavirus vaccine is safe and well-tolerated in healthy toddlers and infants. The primary immunogenicity hypothesis is that the P2-VP8 subunit rotavirus vaccine is immunogenic in infant participants and will induce an immune response in at least 80% of participants in at least one of the study groups.
Interventions
BIOLOGICALP2-VP8 Subunit Vaccine 10mcg
10 mcg
BIOLOGICALP2-VP8 Subunit Vaccine 30 mcg
30 mcg
BIOLOGICALP2-VP8 Subunit Vaccine 60mcg
60 mcg
OTHERPlacebo
Sponsors
PATH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 35 Months
Healthy volunteers
Yes
Inclusion criteria
* healthy infants/toddlers as established by medical history and clinical examination before entering study * age: * toddler cohort: \> or = 2 and \<3 years old at the time of enrollment * infant cohort: \> or = 6 and \<8 weeks at the time of enrollment * parental ability and willingness to provide informed consent * parental intention to remain in the area with the child during the study period.
Exclusion criteria
* Presence of fever on the day of enrollment * Acute disease at the time of enrollment * Concurrent participation in another clinical trial throughout the entire timeframe for this study * Presence of malnutrition or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination that would compromise the participant's health or is likely to result in nonconformance to the protocol * For infant cohort, history of premature birth (\<37 weeks gestation) * History of congenital abdominal disorders, intussusception, or abdominal surgery * Known or suspected impairment of immunological function based on medical history and physical examination * For infant cohort only, prior receipt of rotavirus vaccine * A known sensitivity or allergy to any components of the study vaccine * History of anaphylactic reaction * Major congenital or genetic defect * Participant's parents not able, available or willing to accept active weekly follow-up by the study staff * Has received any immunoglobulin therapy and/or blood products since birth or planned administration during the study period * History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study * Any medical condition in the parents/infant that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent * HIV infection * For toddlers, to be assessed by HIV ELISA * For infants, to be assessed by PCR, if mother is not known to be negative (negative test result between 24 weeks gestation and screening)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Any Non-Serious Adverse Event | 6 mo following first vaccination | all adverse events will be recorded over the duration of the 6 month follow up period. |
| Number of Participants With Vaccine Induced Reactions | 7 days following each dose | Maximum severity of all local reactions or systemic reactogenicity after any vaccination |
| Number of Participants With Serious Adverse Events | within 28 days of a study dose and at any time | Number of participants experiencing a Serious Adverse Event within 28 days of a vaccination and at any time during the study |
| Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Baseline to Day 84 | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit. |
| Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse. | Baseline to day 84 | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third vaccination). Confidence intervals are displayed as percentages. |
| Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Baseline to day 84 | Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | Rotarix vaccination on Day 84 to day 91 | Percent of infants who shed rotavirus at any timepoint after receiving 3 doses of study vaccine and one dose of Rotarix. Infants received Rotarix vaccination beginning on Day 84. Stool specimens were collected from these infants on the 5th, 7th and 9th day following first administration of Rotarix. This test was performed as a novel functional assessment of the ability to suppress local gut multiplication of the vaccine strain contained in Rotarix. |
Countries
South Africa
Participant flow
Recruitment details
Age de-escalation, dose-escalation study enrolling healthy toddlers and infants between 17 March and 29 September 2014 at a single site in South Africa.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Placebo Healthy toddlers aged 2 to \< 3 years receiving placebo | 5 |
| Cohort A 10 mcg P2-VP8 Healthy toddlers aged 2 to \< 3 years receiving low dose P2-VP8 | 13 |
| Cohort A 30 mcg P2-VP8 Healthy toddlers aged 2 to \< 3 years receiving Medium Dose Ps-VP9 | 12 |
| Cohort A 60 mcg P2-VP8 Healthy toddlers aged 2 to \< 3 years receiving High Dose P2-VP8 | 12 |
| Cohort B Placebo Healthy Infants aged 6 to \<8 weeks receiving placeblo | 50 |
| Cohort B 10 mcg P2-VP8 Healthy Infants aged 6 to \<8 weeks receiving Low Dose P2-VP8 | 12 |
| Cohort B 30 mcg P2-VP8 Healthy Infants aged 6 to \<8 weeks receiving Medium Dose P2-VP8 | 50 |
| Cohort B 60 mcg P2-VP8 Healthy Infants aged 6 to \<8 weeks receiving High Dose P2-VP8 | 50 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Moved away from study area | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort A Placebo | Total | Cohort B 60 mcg P2-VP8 | Cohort B 30 mcg P2-VP8 | Cohort B 10 mcg P2-VP8 | Cohort B Placebo | Cohort A 60 mcg P2-VP8 | Cohort A 30 mcg P2-VP8 | Cohort A 10 mcg P2-VP8 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 136.4 weeks | 72.8 weeks | 6.7 weeks | 6.6 weeks | 6.6 weeks | 6.6 weeks | 144.7 weeks | 139.0 weeks | 135.6 weeks |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 202 Participants | 50 Participants | 49 Participants | 12 Participants | 50 Participants | 12 Participants | 12 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment South Africa | 5 participants | 204 participants | 50 participants | 50 participants | 12 participants | 50 participants | 12 participants | 12 participants | 13 participants |
| Sex: Female, Male Female | 3 Participants | 99 Participants | 25 Participants | 23 Participants | 5 Participants | 24 Participants | 6 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 105 Participants | 25 Participants | 27 Participants | 7 Participants | 26 Participants | 6 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 13 | 0 / 12 | 0 / 12 | 0 / 50 | 0 / 12 | 0 / 50 | 2 / 50 |
| other Total, other adverse events | 2 / 5 | 7 / 13 | 6 / 12 | 8 / 12 | 41 / 50 | 11 / 12 | 46 / 50 | 42 / 50 |
| serious Total, serious adverse events | 0 / 5 | 0 / 13 | 0 / 12 | 0 / 12 | 4 / 50 | 0 / 12 | 7 / 50 | 8 / 50 |
Outcome results
Primary
Number of Participants Reporting Any Non-Serious Adverse Event
all adverse events will be recorded over the duration of the 6 month follow up period.
Time frame: 6 mo following first vaccination
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Placebo | Number of Participants Reporting Any Non-Serious Adverse Event | 2 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants Reporting Any Non-Serious Adverse Event | 7 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants Reporting Any Non-Serious Adverse Event | 6 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants Reporting Any Non-Serious Adverse Event | 8 Participants |
| Cohort B Placebo | Number of Participants Reporting Any Non-Serious Adverse Event | 41 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants Reporting Any Non-Serious Adverse Event | 11 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants Reporting Any Non-Serious Adverse Event | 46 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants Reporting Any Non-Serious Adverse Event | 42 Participants |
Primary
Number of Participants With Serious Adverse Events
Number of participants experiencing a Serious Adverse Event within 28 days of a vaccination and at any time during the study
Time frame: within 28 days of a study dose and at any time
Population: All subjects that received at least one dose of P2-VP8 vaccine or placebo
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Placebo | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 0 Participants |
| Cohort A Placebo | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 0 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 0 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 0 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 0 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 0 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 0 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 0 Participants |
| Cohort B Placebo | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 1 Participants |
| Cohort B Placebo | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 4 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 0 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 0 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 6 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 2 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE within 28 days of vaccine receipt | 5 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants With Serious Adverse Events | SAE at any time during follow-up | 6 Participants |
Primary
Number of Participants With Vaccine Induced Reactions
Maximum severity of all local reactions or systemic reactogenicity after any vaccination
Time frame: 7 days following each dose
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Placebo | Number of Participants With Vaccine Induced Reactions | Moderate | 1 Participants |
| Cohort A Placebo | Number of Participants With Vaccine Induced Reactions | None | 3 Participants |
| Cohort A Placebo | Number of Participants With Vaccine Induced Reactions | Severe | 0 Participants |
| Cohort A Placebo | Number of Participants With Vaccine Induced Reactions | Mild | 1 Participants |
| Cohort A Placebo | Number of Participants With Vaccine Induced Reactions | Life Threatening | 0 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Severe | 0 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Mild | 4 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Life Threatening | 0 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | None | 8 Participants |
| Cohort A 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Moderate | 1 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Moderate | 1 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Severe | 0 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Mild | 7 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Life Threatening | 0 Participants |
| Cohort A 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | None | 4 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Moderate | 1 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | None | 6 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Life Threatening | 0 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Severe | 0 Participants |
| Cohort A 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Mild | 5 Participants |
| Cohort B Placebo | Number of Participants With Vaccine Induced Reactions | Moderate | 14 Participants |
| Cohort B Placebo | Number of Participants With Vaccine Induced Reactions | Mild | 29 Participants |
| Cohort B Placebo | Number of Participants With Vaccine Induced Reactions | None | 6 Participants |
| Cohort B Placebo | Number of Participants With Vaccine Induced Reactions | Severe | 1 Participants |
| Cohort B Placebo | Number of Participants With Vaccine Induced Reactions | Life Threatening | 0 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Mild | 10 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Moderate | 0 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Life Threatening | 0 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | None | 2 Participants |
| Cohort B 10 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Severe | 0 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Moderate | 9 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Mild | 35 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Life Threatening | 0 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Severe | 1 Participants |
| Cohort B 30 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | None | 5 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | None | 6 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Life Threatening | 1 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Mild | 37 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Moderate | 6 Participants |
| Cohort B 60 mcg P2-VP8 | Number of Participants With Vaccine Induced Reactions | Severe | 0 Participants |
Primary
Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse.
Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third vaccination). Confidence intervals are displayed as percentages.
Time frame: Baseline to day 84
Population: Enrolled infants who received 3 vaccinations and with pre and post-vaccination immunologic parameters measured
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A Placebo | Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse. | 9 Participants |
| Cohort A 10 mcg P2-VP8 | Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse. | 7 Participants |
| Cohort A 30 mcg P2-VP8 | Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse. | 38 Participants |
| Cohort A 60 mcg P2-VP8 | Number/Percentage of Infant Participants With Anti-P2-VP8 IgA to P[8] Seroresponse. | 32 Participants |
p-value: 0.0165Wilcoxon (Mann-Whitney)
Comparison: Power to detect difference between treatment groups for seroresponse between 50% and 95% for P2-VP8 subunit rotiarivus vaccine calculated based on estimate of 10% loss. 45 evaluable participants in 2 highest doses tolerated in B1 infant cohort, study idesigned to provide \>= 89% and \>= 77% power to detect 35 and 30 percentage points difference, respectively, between the two dose levels and provide \> 95% to detect \>= 40 percentage point difference between a P2-VP8 dose group and placebo group.p-value: <0.0001Wilcoxon (Mann-Whitney)
p-value: <0.0001Wilcoxon (Mann-Whitney)
Primary
Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses
Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit.
Time frame: Baseline to day 84
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Placebo | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Unadjusted Seroresponse | 1 Participants |
| Cohort A Placebo | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Adjusted Seroresponse | 4 Participants |
| Cohort A 10 mcg P2-VP8 | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Adjusted Seroresponse | 12 Participants |
| Cohort A 10 mcg P2-VP8 | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Unadjusted Seroresponse | 12 Participants |
| Cohort A 30 mcg P2-VP8 | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Adjusted Seroresponse | 46 Participants |
| Cohort A 30 mcg P2-VP8 | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Unadjusted Seroresponse | 46 Participants |
| Cohort A 60 mcg P2-VP8 | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Adjusted Seroresponse | 47 Participants |
| Cohort A 60 mcg P2-VP8 | Number/Percentage of Infants With Anti-P2-VP8 IgG to P[8] Seroresponses | Unadjusted Seroresponse | 46 Participants |
Comparison: Pair-wise comparisons between Cohort B Placebo group and the active vaccination groups were peformedp-value: <0.0001Wilcoxon (Mann-Whitney)
p-value: <0.0001Wilcoxon (Mann-Whitney)
p-value: 0.0006Wilcoxon (Mann-Whitney)
Primary
Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8])
Seroresponse is defined as 4 fold rise in Geometric Mean Titer (GMT) between pre-(baseline) and post vaccination (4 weeks after third injection).An unadjusted serioresponse was defined as an increase of 4 times or more in titers between baseline and 4 weeks after the 3rd injection. Adjusted IgG and neutralizing antibody post injection titres accounted for the decay in maternal antibodies using the half-life calculated from participants in the placebo group with detectable baseline titers higher than those at the post injection visit.
Time frame: Baseline to Day 84
Population: Enrolled infants who received placebo, 10 mcg, 30 mcg or 60 mcg V2-VP8.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Placebo | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Unadjusted seroresponse to neutralizing antibodies | 0 Participants |
| Cohort A Placebo | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Adjusted seroresponse to neutralizing antibodies | 3 Participants |
| Cohort A 10 mcg P2-VP8 | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Adjusted seroresponse to neutralizing antibodies | 12 Participants |
| Cohort A 10 mcg P2-VP8 | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Unadjusted seroresponse to neutralizing antibodies | 7 Participants |
| Cohort A 30 mcg P2-VP8 | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Adjusted seroresponse to neutralizing antibodies | 40 Participants |
| Cohort A 30 mcg P2-VP8 | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Unadjusted seroresponse to neutralizing antibodies | 17 Participants |
| Cohort A 60 mcg P2-VP8 | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Adjusted seroresponse to neutralizing antibodies | 40 Participants |
| Cohort A 60 mcg P2-VP8 | Number/Percentage of Infants With Neutralizing Antibody Response to WA Strain (G1[P8]) | Unadjusted seroresponse to neutralizing antibodies | 7 Participants |
Comparison: A pair wise comparison between the Adjusted Seroresponses in the placebo group and the Group B 10 mcg P2-VP8 was performed.p-value: 0.0004Wilcoxon (Mann-Whitney)
Comparison: A pair wise comparison between the Adjusted Seroresponses in the placebo group and the Cohort B 30 mcg P2-VP8 vaccine group was performed.p-value: <0.0001Wilcoxon (Mann-Whitney)
Comparison: A pair-wise comparison between the Adjusted Seroresponses in Cohort B Placebo group and the Cohort B P2-VP8 group was performed.p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo.
Percent of infants who shed rotavirus at any timepoint after receiving 3 doses of study vaccine and one dose of Rotarix. Infants received Rotarix vaccination beginning on Day 84. Stool specimens were collected from these infants on the 5th, 7th and 9th day following first administration of Rotarix. This test was performed as a novel functional assessment of the ability to suppress local gut multiplication of the vaccine strain contained in Rotarix.
Time frame: Rotarix vaccination on Day 84 to day 91
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A Placebo | Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | No shedding of rotavirus | 27 Participants |
| Cohort A Placebo | Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | Any Timepoint - Rotavirus shedding | 17 Participants |
| Cohort A 10 mcg P2-VP8 | Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | No shedding of rotavirus | 39 Participants |
| Cohort A 10 mcg P2-VP8 | Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | Any Timepoint - Rotavirus shedding | 6 Participants |
| Cohort A 30 mcg P2-VP8 | Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | No shedding of rotavirus | 37 Participants |
| Cohort A 30 mcg P2-VP8 | Rotavirus Shedding After Administration of Rotarix in Infants Receiving 3 Doses of Vaccine or Placebo. | Any Timepoint - Rotavirus shedding | 9 Participants |