Trial Outcomes & Findings for Evaluation of the Human Rotavirus Vaccine at Varying Schedules and Doses in Rural Ghana (NCT NCT01575197)

NCT ID: NCT01575197

Last Updated: 2015-06-01

Results Overview

Anti-rotavirus IgA seroconversion will be defined as the detection of anti-rotavirus IgA antibodies at a concentration ≥20 U/mL post-vaccination in infants seronegative for anti-rotavirus IgA pre-vaccination as measured by Enzyme Immunoassay (EIA).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

456 participants

Primary outcome timeframe

4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)

Results posted on

2015-06-01

Participant Flow

Participant milestones

Participant milestones
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 10 & 14 Weeks
Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 10 \& 14 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6, 10, \& 14 weeks of age.
Overall Study
STARTED
152
152
152
Overall Study
COMPLETED
149
143
146
Overall Study
NOT COMPLETED
3
9
6

Reasons for withdrawal

Reasons for withdrawal
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 10 & 14 Weeks
Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 10 \& 14 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6, 10, \& 14 weeks of age.
Overall Study
Migration out of study area
1
5
4
Overall Study
SAE
0
1
0
Overall Study
Lost to Follow-up
0
1
0
Overall Study
Withdrawal by Subject
0
1
1
Overall Study
Protocol Violation
2
1
1

Baseline Characteristics

Evaluation of the Human Rotavirus Vaccine at Varying Schedules and Doses in Rural Ghana

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
n=150 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 10 & 14 Weeks
n=149 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 10 \& 14 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
n=151 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, \& 14 weeks of age.
Total
n=450 Participants
Total of all reporting groups
Age, Continuous
6.2 weeks
STANDARD_DEVIATION 0.2 • n=5 Participants
6.2 weeks
STANDARD_DEVIATION 0.2 • n=7 Participants
6.2 weeks
STANDARD_DEVIATION 0.2 • n=5 Participants
6.2 weeks
STANDARD_DEVIATION 0.2 • n=4 Participants
Sex: Female, Male
Female
68 Participants
n=5 Participants
79 Participants
n=7 Participants
72 Participants
n=5 Participants
219 Participants
n=4 Participants
Sex: Female, Male
Male
82 Participants
n=5 Participants
70 Participants
n=7 Participants
79 Participants
n=5 Participants
231 Participants
n=4 Participants
Region of Enrollment
Ghana
150 participants
n=5 Participants
149 participants
n=7 Participants
151 participants
n=5 Participants
450 participants
n=4 Participants

PRIMARY outcome

Timeframe: 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)

Population: Per-protocol analysis population--participants who (1) meet inclusion/exclusion criteria; (2) seronegative pre- vaccination; (3) concomitant administration of HRV and oral polio vaccine (OPV) according to Group schedule, (4) study visits in window periods (vaccination visits 4 weeks + 2 weeks), and (5) valid serology results.

Anti-rotavirus IgA seroconversion will be defined as the detection of anti-rotavirus IgA antibodies at a concentration ≥20 U/mL post-vaccination in infants seronegative for anti-rotavirus IgA pre-vaccination as measured by Enzyme Immunoassay (EIA).

Outcome measures

Outcome measures
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
n=142 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
n=143 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, \& 14 weeks of age.
Immunoglobulin A (IgA) Seroconversion: 6 & 10 Week vs. 6, 10, & 14 Week Vaccination Schedules
28.9 percentage of participants
Interval 22.1 to 36.8
43.4 percentage of participants
Interval 35.5 to 51.6

SECONDARY outcome

Timeframe: 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)

Population: Per-protocol analysis population--participants who (1) meet inclusion/exclusion criteria; (2) seronegative pre- vaccination; (3) concomitant administration of HRV and OPV according to Group schedule, (4) study visits in window periods (vaccination visits 4 weeks + 2 weeks), and (5) valid serology results.

Anti-rotavirus IgA seroconversion will be defined as the detection of anti-rotavirus IgA antibodies at a concentration ≥20 U/mL post-vaccination in infants seronegative for anti-rotavirus IgA pre- vaccination as measured by EIA.

Outcome measures

Outcome measures
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
n=142 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
n=139 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, \& 14 weeks of age.
IgA Seroconversion: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedules
28.9 percentage of participants
Interval 22.1 to 36.8
37.4 percentage of participants
Interval 29.8 to 45.7

SECONDARY outcome

Timeframe: 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)

Population: Per-protocol analysis population--participants who (1) meet inclusion/exclusion criteria; (2) seronegative pre- vaccination; (3) concomitant administration of HRV and OPV according to Group schedule, (4) study visits in window periods (vaccination visits 4 weeks + 2 weeks), and (5) valid serology results.

IgA GMTs measured by EIA will be compared post-vaccination between participants receiving Rotarix at 6 and 10 weeks of age and those receiving Rotarix at 6, 10, and 14 weeks of age. For participants in Group 1, where post-vaccination response was measured at both 14 and 18 weeks of age, the highest response between these two visits was used as the final response for comparison.

Outcome measures

Outcome measures
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
n=142 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
n=143 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, \& 14 weeks of age.
IgA Geometric Mean Titers (GMTs): 6 & 10 Week vs. 6, 10, & 14 Week Vaccination Schedules
22.5 titers
Interval 17.4 to 28.2
32.6 titers
Interval 24.7 to 43.2

SECONDARY outcome

Timeframe: 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)

Population: Per-protocol analysis population--participants who (1) meet inclusion/exclusion criteria; (2) seronegative pre- vaccination; (3) concomitant administration of HRV and OPV according to Group schedule, (4) study visits in window periods (vaccination visits 4 weeks + 2 weeks), and (5) valid serology results.

IgA GMTs measured by EIA will be compared post-vaccination between participants receiving Rotarix at 6 and 10 weeks of age and those receiving Rotarix at 10 and 14 weeks of age. For participants in Group 1, where post-vaccination response was measured at both 14 and 18 weeks of age, the highest response between these two visits was used as the final response for comparison.

Outcome measures

Outcome measures
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
n=142 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
n=139 Participants
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, \& 14 weeks of age.
IgA GMTs: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedule
22.1 titers
Interval 17.4 to 28.2
26.5 titers
Interval 20.7 to 34.0

SECONDARY outcome

Timeframe: Baseline, 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)

The number and percentage of participants demonstrating IgA seroconversion post-vaccination as defined above in infants seronegative for anti-rotavirus IgA pre- vaccination using the EIA assay) by EIA pre- and post-vaccination will be compared between participants in each group who had low as compared to high rotavirus immunoglobulin G (IgG) antibody levels pre-vaccination (i.e., at 6 weeks in Groups 1 and 3 and at 10 weeks in Group 2) as measured by Enzyme linked immunosorbent assay (ELISA). Low and high IgG categories will be determined based on the IgG antibody level distribution.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 4 and 7 post each study vaccination

Vaccine-type rotavirus shedding in the stool at 4 (±1 day) and 7 days (±1 day) following each Rotarix vaccination will be identified using EIA for rotavirus antigens and compared to baseline levels obtained just prior to each study vaccination. If shedding in stool is detected at either time point (per manufacturer's specifications) following each Rotarix vaccination, this will be considered evidence of vaccine take.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Throughout study period; Group 1: from enrollment through approximately 8 weeks of study participation, Groups 2 & 3: from enrollment through approximately 12 weeks of study participation

Serious adverse events (SAEs) occurring at anytime during the study will be measured as observed by study staff and/or reported by parent at any time. SAEs will be subcategorized according to treatment group as those deemed related to vaccination or not by an independent study monitor.

Outcome measures

Outcome data not reported

Adverse Events

Rotavirus Vaccine at Age 6 & 10 Weeks

Serious events: 1 serious events
Other events: 78 other events
Deaths: 0 deaths

Rotavirus Vaccine at Age 10 & 14 Weeks

Serious events: 4 serious events
Other events: 76 other events
Deaths: 0 deaths

Rotavirus Vaccine at Age 6,10,&14 Weeks

Serious events: 3 serious events
Other events: 71 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
n=152 participants at risk
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 10 & 14 Weeks
n=152 participants at risk
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 10 \& 14 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
n=151 participants at risk
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, \& 14 weeks of age.
Gastrointestinal disorders
Gastroenteritis
0.66%
1/152 • Number of events 1 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/152 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.66%
1/151 • Number of events 1 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Infections and infestations
Abscess of the Left Jaw
0.00%
0/152 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.66%
1/152 • Number of events 1 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/151 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Infections and infestations
Acute Respiratory Infection
0.00%
0/152 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/152 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
1.3%
2/151 • Number of events 2 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Congenital, familial and genetic disorders
Congenital Hydrocephalus
0.00%
0/152 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.66%
1/152 • Number of events 2 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/151 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Infections and infestations
Gluteal Abscess/ Sepsis
0.00%
0/152 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
1.3%
2/152 • Number of events 2 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/151 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.

Other adverse events

Other adverse events
Measure
Rotavirus Vaccine at Age 6 & 10 Weeks
n=152 participants at risk
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 \& 10 weeks of age.
Rotavirus Vaccine at Age 10 & 14 Weeks
n=152 participants at risk
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 10 \& 14 weeks of age.
Rotavirus Vaccine at Age 6,10,&14 Weeks
n=151 participants at risk
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, \& 14 weeks of age.
Gastrointestinal disorders
Abdominal Pain/Diarrhea
17.8%
27/152 • Number of events 27 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
24.3%
37/152 • Number of events 37 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
17.9%
27/151 • Number of events 27 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Infections and infestations
Infection/Abscess/Boil/Sepsis
19.1%
29/152 • Number of events 29 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
16.4%
25/152 • Number of events 25 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
17.2%
26/151 • Number of events 26 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Respiratory, thoracic and mediastinal disorders
Respiratory infection
28.9%
44/152 • Number of events 44 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
29.6%
45/152 • Number of events 45 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
28.5%
43/151 • Number of events 43 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Infections and infestations
Fever
6.6%
10/152 • Number of events 10 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
4.6%
7/152 • Number of events 7 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/151 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Infections and infestations
Malaria
9.2%
14/152 • Number of events 14 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
9.9%
15/152 • Number of events 15 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
7.9%
12/151 • Number of events 12 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Ear and labyrinth disorders
Otitis Media
0.66%
1/152 • Number of events 1 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/152 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.66%
1/151 • Number of events 1 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
Infections and infestations
Irritable/refusing to feed
0.66%
1/152 • Number of events 1 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
1.3%
2/152 • Number of events 2 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
0.00%
0/151 • Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.

Additional Information

Senior Clinical Research Scientist

PATH

Phone: 206-285-3500

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60