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

Phase 4

Completed

Conditions: Rotavirus Gastroenteritis

Interventions: Biological: Human Rotavirus Vaccine

Registration Number: NCT01575197

Lead Sponsor: PATH

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 456

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rotavirus Vaccine at age 6 & 10 weeks	Human Rotavirus Vaccine	Participants are provided with the Human Rotavirus Vaccine (HRV) at 6 \& 10 weeks of age.
Rotavirus vaccine at age 6,10,&14 weeks	Human Rotavirus Vaccine	Participants are provided with the Human Rotavirus Vaccine (HRV) at 6, 10, \& 14 weeks of age.
Rotavirus vaccine at age 10 & 14 weeks	Human Rotavirus Vaccine	Participants are provided with the Human Rotavirus Vaccine (HRV) at 10 \& 14 weeks of age.

Primary Outcome Measures

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

Secondary Outcome Measures

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