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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

Tracking Information
First Submitted Date  ICMJE April 6, 2012
First Posted Date  ICMJE April 11, 2012
Results First Submitted Date  ICMJE April 28, 2015
Results First Posted Date  ICMJE June 1, 2015
Last Update Posted Date June 1, 2015
Study Start Date  ICMJE September 2012
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2015)
Immunoglobulin A (IgA) Seroconversion: 6 & 10 Week vs. 6, 10, & 14 Week Vaccination Schedules [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 9, 2012)
IgA seroconversion: 6 & 10 week vs. 6, 10, & 14 week vaccination schedules [ Time Frame: 4-weeks post-vaccination ]
Anti-rotavirus IgA seroconversion will be defined as the detection of anti-rotavirus IgA antibodies at a concentration ≥20 U/mL at 14 weeks (for the 6 and 10 week arm) or 18 weeks of age (for the 6, 10, and 14 week arm) in infants seronegative for anti-rotavirus IgA pre-vaccination as measured by EIA.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2015)
  • IgA Seroconversion: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedules [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
  • SAE Assessment [ 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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2012)
  • IgA Seroconversion: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedules [ Time Frame: 4-weeks post-vaccination ]
    Anti-rotavirus IgA seroconversion will be defined as the detection of anti-rotavirus IgA antibodies at a concentration ≥20 U/mL at 14 weeks (for the 6 and 10 week arm) or 18 weeks of age (for the 10 and 14 week arm) in infants seronegative for anti-rotavirus IgA pre- vaccination as measured by EIA.
  • IgA GMTs: 6 & 10 week vs. 6, 10, & 14 week vaccination schedules [ Time Frame: 4- weeks post-vaccination ]
    IgA GMTs measured by EIA will be compared at 14 (Group 1) or 18 (group 3) weeks of age between participants receiving Rotarix at 6 and 10 weeks of age and those receiving Rotarix at 6, 10, and 14 weeks of age.
  • IgA GMTs: 6 & 10 Week vs. 10 & 14 Week Vaccination Schedule [ Time Frame: 4-weeks post-vaccination ]
    IgA GMTs measured by EIA will be compared at 14 (Group 1) or 18 (group 2) weeks of age between participants receiving Rotarix at 6 and 10 weeks of age and those receiving Rotarix at 10 and 14 weeks of age.
  • Baseline IgG levels: Impact on IgA seroconversion post-vaccination [ Time Frame: Baseline and 4-weeks post-vaccination ]
    The number and percentage of participants demonstrating IgA seroconversion at 14 or 18 weeks as defined above in infants seronegative for anti-rotavirus IgA pre- vaccination using the EIA assay) by EIA between 6 and 14 or 18 weeks of age (as defined above) will be compared between participants mL 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 ELISA. Low and high IgG categories will be determined based on the IgG antibody level distribution.
  • Vaccine-type Rotavirus Shedding in Stool [ Time Frame: 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.
  • SAE Assessment [ 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 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Human Rotavirus Vaccine at Varying Schedules and Doses in Rural Ghana
Official Title  ICMJE Immunogenicity of the Human Rotavirus Vaccine (Rotarix™) at Varying Schedules, Doses, and Ages in Rural Ghana
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Rotavirus Gastroenteritis
Intervention  ICMJE Biological: Human Rotavirus Vaccine
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.
Other Name: Rotarix
Study Arms  ICMJE
  • Active Comparator: Rotavirus Vaccine at age 6 & 10 weeks
    Participants are provided with the Human Rotavirus Vaccine (HRV) at 6 & 10 weeks of age.
    Intervention: Biological: Human Rotavirus Vaccine
  • Experimental: Rotavirus vaccine at age 10 & 14 weeks
    Participants are provided with the Human Rotavirus Vaccine (HRV) at 10 & 14 weeks of age.
    Intervention: Biological: Human Rotavirus Vaccine
  • Experimental: Rotavirus vaccine at age 6,10,&14 weeks
    Participants are provided with the Human Rotavirus Vaccine (HRV) at 6, 10, & 14 weeks of age.
    Intervention: Biological: Human Rotavirus Vaccine
Publications * Armah G, Lewis KD, Cortese MM, Parashar UD, Ansah A, Gazley L, Victor JC, McNeal MM, Binka F, Steele AD. A Randomized, Controlled Trial of the Impact of Alternative Dosing Schedules on the Immune Response to Human Rotavirus Vaccine in Rural Ghanaian Infants. J Infect Dis. 2016 Jun 1;213(11):1678-85. doi: 10.1093/infdis/jiw023. Epub 2016 Jan 27. Erratum in: J Infect Dis. 2016 Oct 1;214(7):1127.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 9, 2012)
456
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2013
Actual Primary Completion Date February 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 42 Days to 55 Days   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Ghana
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01575197
Other Study ID Numbers  ICMJE GHANA-HRV-01
OPP1017334 ( Other Grant/Funding Number: Bill and Melinda Gates Foundation )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PATH
Study Sponsor  ICMJE PATH
Collaborators  ICMJE
  • Noguchi Memorial Institute for Medical Research
  • Navrongo Health Research Center
  • Centers for Disease Control and Prevention
Investigators  ICMJE
Principal Investigator: George Armah, PhD Noguchi Memorial Institute for Medical Research
PRS Account PATH
Verification Date April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP