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

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ClinicalTrials.gov Identifier: NCT01575197
Recruitment Status : Completed
First Posted : April 11, 2012
Results First Posted : June 1, 2015
Last Update Posted : June 1, 2015
Sponsor:
Collaborators:
Noguchi Memorial Institute for Medical Research
Navrongo Health Research Center
Centers for Disease Control and Prevention
Information provided by (Responsible Party):
PATH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Rotavirus Gastroenteritis
Intervention Biological: Human Rotavirus Vaccine
Enrollment 456
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks
Hide Arm/Group Description Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6 & 10 weeks of age. Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 10 & 14 weeks of age. Human rotavirus vaccine (HRV) was administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6, 10, & 14 weeks of age.
Period Title: Overall Study
Started 152 152 152
Completed 149 143 146
Not Completed 3 9 6
Reason Not Completed
Migration out of study area             1             5             4
SAE             0             1             0
Lost to Follow-up             0             1             0
Withdrawal by Subject             0             1             1
Protocol Violation             2             1             1
Arm/Group Title Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks Total
Hide Arm/Group Description Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 & 10 weeks of age. Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 10 & 14 weeks of age. Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, & 14 weeks of age. Total of all reporting groups
Overall Number of Baseline Participants 150 149 151 450
Hide Baseline Analysis Population Description
All enrolled subjects who received at least one rotavirus vaccine dose and are IgA seronegative (< 20 U/mL) at 6 (Groups 1 and 3) or 10 (Group 2) weeks of age at baseline.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 150 participants 149 participants 151 participants 450 participants
6.2  (0.2) 6.2  (0.2) 6.2  (0.2) 6.2  (0.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 150 participants 149 participants 151 participants 450 participants
Female
68
  45.3%
79
  53.0%
72
  47.7%
219
  48.7%
Male
82
  54.7%
70
  47.0%
79
  52.3%
231
  51.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Ghana Number Analyzed 150 participants 149 participants 151 participants 450 participants
150 149 151 450
1.Primary Outcome
Title Immunoglobulin A (IgA) Seroconversion: 6 & 10 Week vs. 6, 10, & 14 Week Vaccination Schedules
Hide Description 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).
Time Frame 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks
Hide Arm/Group Description:
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 & 10 weeks of age.
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, & 14 weeks of age.
Overall Number of Participants Analyzed 142 143
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.9
(22.1 to 36.8)
43.4
(35.5 to 51.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rotavirus Vaccine at Age 6 & 10 Weeks, Rotavirus Vaccine at Age 6,10,&14 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
2.Secondary Outcome
Title IgA Seroconversion: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedules
Hide Description 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.
Time Frame 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks
Hide Arm/Group Description:
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 & 10 weeks of age.
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 10 & 14 weeks of age.
Overall Number of Participants Analyzed 142 139
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
28.9
(22.1 to 36.8)
37.4
(29.8 to 45.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rotavirus Vaccine at Age 6 & 10 Weeks, Rotavirus Vaccine at Age 10 & 14 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.16
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title IgA Geometric Mean Titers (GMTs): 6 & 10 Week vs. 6, 10, & 14 Week Vaccination Schedules
Hide Description 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.
Time Frame 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks
Hide Arm/Group Description:
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 & 10 weeks of age.
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, & 14 weeks of age.
Overall Number of Participants Analyzed 142 143
Geometric Mean (95% Confidence Interval)
Unit of Measure: titers
22.5
(17.4 to 28.2)
32.6
(24.7 to 43.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rotavirus Vaccine at Age 6 & 10 Weeks, Rotavirus Vaccine at Age 6,10,&14 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title IgA GMTs: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedule
Hide Description 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.
Time Frame 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks
Hide Arm/Group Description:
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 & 10 weeks of age.
Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 10 & 14 weeks of age.
Overall Number of Participants Analyzed 142 139
Geometric Mean (95% Confidence Interval)
Unit of Measure: titers
22.1
(17.4 to 28.2)
26.5
(20.7 to 34.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rotavirus Vaccine at Age 6 & 10 Weeks, Rotavirus Vaccine at Age 10 & 14 Weeks
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.30
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Baseline Immunoglobulin G (IgG) Levels: Impact on IgA Seroconversion Post-vaccination
Hide Description 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.
Time Frame Baseline, 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group)
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Vaccine-type Rotavirus Shedding in Stool
Hide Description 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.
Time Frame Days 4 and 7 post each study vaccination
Outcome Measure Data Not Reported
7.Secondary Outcome
Title SAE Assessment
Hide Description 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.
Time Frame 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
Outcome Measure Data Not Reported
Time Frame Adverse events: 1 month following each study vaccination; serious adverse events: throughout study period, up to 5 months
Adverse Event Reporting Description Any participant receiving one or more doses of rotavirus vaccine was included in this analysis.
 
Arm/Group Title Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks
Hide Arm/Group Description Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6 & 10 weeks of age. Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 10 & 14 weeks of age. Human rotavirus vaccine was administered concomitantly with other routine EPI vaccinations at 6, 10, & 14 weeks of age.
All-Cause Mortality
Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/152 (0.66%)      4/152 (2.63%)      3/151 (1.99%)    
Congenital, familial and genetic disorders       
Congenital Hydrocephalus   0/152 (0.00%)  0 1/152 (0.66%)  2 0/151 (0.00%)  0
Gastrointestinal disorders       
Gastroenteritis   1/152 (0.66%)  1 0/152 (0.00%)  0 1/151 (0.66%)  1
Infections and infestations       
Abscess of the Left Jaw   0/152 (0.00%)  0 1/152 (0.66%)  1 0/151 (0.00%)  0
Acute Respiratory Infection   0/152 (0.00%)  0 0/152 (0.00%)  0 2/151 (1.32%)  2
Gluteal Abscess/ Sepsis   0/152 (0.00%)  0 2/152 (1.32%)  2 0/151 (0.00%)  0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Rotavirus Vaccine at Age 6 & 10 Weeks Rotavirus Vaccine at Age 10 & 14 Weeks Rotavirus Vaccine at Age 6,10,&14 Weeks
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   78/152 (51.32%)      76/152 (50.00%)      71/151 (47.02%)    
Ear and labyrinth disorders       
Otitis Media   1/152 (0.66%)  1 0/152 (0.00%)  0 1/151 (0.66%)  1
Gastrointestinal disorders       
Abdominal Pain/Diarrhea   27/152 (17.76%)  27 37/152 (24.34%)  37 27/151 (17.88%)  27
Infections and infestations       
Infection/Abscess/Boil/Sepsis   29/152 (19.08%)  29 25/152 (16.45%)  25 26/151 (17.22%)  26
Fever   10/152 (6.58%)  10 7/152 (4.61%)  7 0/151 (0.00%)  0
Malaria   14/152 (9.21%)  14 15/152 (9.87%)  15 12/151 (7.95%)  12
Irritable/refusing to feed   1/152 (0.66%)  1 2/152 (1.32%)  2 0/151 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Respiratory infection   44/152 (28.95%)  44 45/152 (29.61%)  45 43/151 (28.48%)  43
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Clinical Research Scientist
Organization: PATH
Phone: 206-285-3500
EMail: klewis@path.org
Layout table for additonal information
Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT01575197    
Other Study ID Numbers: GHANA-HRV-01
OPP1017334 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
First Submitted: April 6, 2012
First Posted: April 11, 2012
Results First Submitted: April 28, 2015
Results First Posted: June 1, 2015
Last Update Posted: June 1, 2015