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

Study Overview
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Brief Summary
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The purpose of this study is to determine whether giving the Human Rotavirus Vaccine on alternate dosing schedules will enhance the immune response to the vaccine in a low-resource, high-burden country in Africa. Alternate dosing schedules studied include giving the 2-dose vaccine schedule at a slightly older age and giving an additional dose of the vaccine.

Official Title
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Immunogenicity of the Human Rotavirus Vaccine (Rotarix™) at Varying Schedules, Doses, and Ages in Rural Ghana

Conditions
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Rotavirus Gastroenteritis

Intervention / Treatment
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* Biological: Human Rotavirus Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 42 and 55 days of age at the time of enrollment. Healthy infant free of chronic or serious medical condition as determined by history and physical examination at the time of study enrollment. Parents/guardians of each subject are able to understand and follow study procedures and agree to participate in the study by providing parental/guardian permission. Exclusion Criteria: If child has previously had intussusception or abdominal surgery. Use of any immunosuppressive drugs or immunoglobulin and/or blood product use since birth or anticipated during study period. Current enrollment in any other intervention trial or use of any investigational drug or vaccine throughout the study period. Birthweight less than 2000 grams or gestation < 36 weeks, if this information is available. Any subject who reports plan to leave the study area before the completion of the study (i.e., relocation, migration, etc.). Another child living in the same compound is already enrolled in the trial (i.e., only one participant can be enrolled per compound). After the rotavirus vaccine is introduced into the routine EPI system in Navrongo: Another child in the compound is less than 16 weeks of age. The child has received rotavirus vaccine outside of this study.

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 55 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rotavirus Vaccine at age 6 & 10 weeks<br>Participants are provided with the Human Rotavirus Vaccine (HRV) at 6 & 10 weeks of age. | Biological: Human Rotavirus Vaccine<br>* Rotavirus vaccine will be administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6 & 10 weeks of age, 10 & 14 weeks of age, or 6, 10, & 14 weeks of age, depending on study arm assignment.<br>* Other names: Rotarix;|
| Experimental: Rotavirus vaccine at age 10 & 14 weeks<br>Participants are provided with the Human Rotavirus Vaccine (HRV) at 10 & 14 weeks of age. | Biological: Human Rotavirus Vaccine<br>* Rotavirus vaccine will be administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6 & 10 weeks of age, 10 & 14 weeks of age, or 6, 10, & 14 weeks of age, depending on study arm assignment.<br>* Other names: Rotarix;|
| Experimental: Rotavirus vaccine at age 6,10,&14 weeks<br>Participants are provided with the Human Rotavirus Vaccine (HRV) at 6, 10, & 14 weeks of age. | Biological: Human Rotavirus Vaccine<br>* Rotavirus vaccine will be administered concomitantly with other routine Expanded Programme on Immunization (EPI) vaccinations at 6 & 10 weeks of age, 10 & 14 weeks of age, or 6, 10, & 14 weeks of age, depending on study arm assignment.<br>* Other names: Rotarix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunoglobulin A (IgA) Seroconversion: 6 & 10 Week vs. 6, 10, & 14 Week Vaccination Schedules | 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). | 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgA Seroconversion: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedules | 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. | 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group) | 
| IgA Geometric Mean Titers (GMTs): 6 & 10 Week vs. 6, 10, & 14 Week Vaccination Schedules | 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. | 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group) | 
| IgA GMTs: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedule | 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. | 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group) | 
| Baseline Immunoglobulin G (IgG) Levels: Impact on IgA Seroconversion Post-vaccination | 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. | Baseline, 4-weeks post-vaccination (All Groups) and 8 weeks post-vaccination (6 & 10 week Group) | 
| Vaccine-type Rotavirus Shedding in Stool | 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. | Days 4 and 7 post each study vaccination | 
| SAE Assessment | 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. | 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 |