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The Effects of Increased Inoculum on Oral Rotavirus Vaccine Take and Immunogenicity

Primary Purpose

Rotavirus Infection, Vaccine Response Impaired, Vaccine Virus Shedding

Status
Completed
Phase
Phase 4
Locations
Bangladesh
Study Type
Interventional
Intervention
Rotarix, dose 1
Rotarix, dose 2
Placebo (for Rotarix dose 2)
Sponsored by
University of Vermont
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Rotavirus Infection focused on measuring Rotavirus, Oral vaccines, Vaccine underperformance, Vaccine shedding

Eligibility Criteria

undefined - 15 Weeks (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Generally healthy infant (as determined by medical officers)
  2. Age 0-7 days at enrolment
  3. Mother willing and able to provide signed informed consent
  4. Mother willing to allow infant to be vaccinated according to study schedule
  5. Mother willing to allow biological specimens, including blood, stool, and saliva, to be collected from infant according to study protocol
  6. Mother willing and able to adhere to study schedule

Exclusion Criteria:

  1. Obvious congenital malformation
  2. Birth weight (if known) or enrolment weight (if birth weight unknown) < 2000 gm
  3. Known immunocompromising condition in infant
  4. Enrolment in other vaccine research trials
  5. Other household member enrolled in this study

Sites / Locations

  • International Center for Diarrhoeal Disease Research, Bangladesh (icddr,b)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Rotarix, single dose

Rotarix, double dose

Arm Description

Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life

Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life

Outcomes

Primary Outcome Measures

Number (or Percentage) of Infants in Each Study Arm Who Test Positive for Fecal Rotavirus Vaccine-strain Virus Shedding Post-vaccination
This will be an aggregate measure demonstrating a change from baseline. Infants will have stool collected immediately prior to Rotarix vaccination at weeks 6 and 10 of life, then 4, 7, and 14 days following each dose (i.e. last assessment at week 12 of life). Each specimen will be assessed for vaccine-strain virus (i.e. fecal vaccine shedding) at each time point by polymerase chain reaction. Any child who has a change in fecal vaccine shedding status, from negative at baseline (6 weeks) to positive at any subsequent time point, will be categorized as having met the outcome measure for positive fecal vaccine shedding.
Number (or Percentage) of Infants in Each Study Arm With Rotavirus-specific Plasma Immunoglobulin A (IgA) Seroconversion Post-vaccination
This outcome will measure seroconversion, i.e. the change in plasma rotavirus-specific IgA concentration at week 14 of life compared to week 6 of life (baseline). Blood will be collected from infants prior to the first dose of Rotarix at week 6 of life and again at week 14 of life (4 weeks following the second dose) for measurement of plasma rotavirus-specific IgA by enzyme immunoassay. Infants will be assessed for seroconversion (IgA concentration <=20 U/mL pre-vaccination and >20 post-vaccination). Infants who demonstrate rotavirus-specific IgA seroconversion will be categorized as having met the outcome measure.
Number (or Percentage) of Infants in Each Study Arm With Successful Vaccine Take, Defined as Positive Fecal Vaccine Shedding Post-vaccination OR Rotavirus-specific Plasma IgA Seroconversion Post-vaccination
Vaccine take is an aggregate, dichotomous immunogenicity measure (successful vaccine take vs no vaccine take). Infants positive for either fecal vaccine shedding OR plasma rotavirus-specific IgA seroconversion (as described in Outcomes 1 and 2, respectively) will be categorized as having met the outcome measure of successful vaccine take. Those who met neither outcome will be categorized as no vaccine take.

Secondary Outcome Measures

Full Information

First Posted
December 1, 2016
Last Updated
July 17, 2020
Sponsor
University of Vermont
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Charles H. Hood Foundation, Thrasher Research Fund
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1. Study Identification

Unique Protocol Identification Number
NCT02992197
Brief Title
The Effects of Increased Inoculum on Oral Rotavirus Vaccine Take and Immunogenicity
Official Title
A Double-blind, Randomized Controlled Trial of the Effect of Vaccine Inoculum on Oral Rotavirus Vaccine (Rotarix, GlaxoSmithKline) Take and Immunogenicity in Dhaka, Bangladesh
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
June 12, 2017 (Actual)
Primary Completion Date
June 7, 2018 (Actual)
Study Completion Date
June 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Vermont
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Charles H. Hood Foundation, Thrasher Research Fund

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Rotavirus is the leading cause of diarrhea in children worldwide. Oral rotavirus vaccines work remarkably well in high-income countries, but for unclear reasons they underperform in low-income countries. A double-blind, randomized control trial will be performed to evaluate whether using a higher dose of a currently licensed vaccine (Rotarix, GlaxoSmithKline) can improve immune responses among infants in Dhaka, Bangladesh. Infants will be randomized 1:1 to receive either a standard or a double dose of Rotarix at 6 and 10 weeks of life. Infants will be assessed for fecal vaccine shedding and serum rotavirus-specific IgA responses to determine vaccine immunogenicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rotavirus Infection, Vaccine Response Impaired, Vaccine Virus Shedding
Keywords
Rotavirus, Oral vaccines, Vaccine underperformance, Vaccine shedding

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
220 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rotarix, single dose
Arm Type
Active Comparator
Arm Description
Rotarix 1.5 mL (standard single dose) and 1.5 mL of placebo by mouth (sterile, pharmacy-grade water) at both 6 and 10 weeks of life
Arm Title
Rotarix, double dose
Arm Type
Experimental
Arm Description
Rotarix 3 mL by mouth (two standard doses administered simultaneously) at both 6 and 10 weeks of life
Intervention Type
Biological
Intervention Name(s)
Rotarix, dose 1
Intervention Description
Rotarix, dose 1
Intervention Type
Biological
Intervention Name(s)
Rotarix, dose 2
Intervention Description
Rotarix, dose 2
Intervention Type
Drug
Intervention Name(s)
Placebo (for Rotarix dose 2)
Intervention Description
Sterile water to provide volume equivalent as a second dose of Rotarix
Primary Outcome Measure Information:
Title
Number (or Percentage) of Infants in Each Study Arm Who Test Positive for Fecal Rotavirus Vaccine-strain Virus Shedding Post-vaccination
Description
This will be an aggregate measure demonstrating a change from baseline. Infants will have stool collected immediately prior to Rotarix vaccination at weeks 6 and 10 of life, then 4, 7, and 14 days following each dose (i.e. last assessment at week 12 of life). Each specimen will be assessed for vaccine-strain virus (i.e. fecal vaccine shedding) at each time point by polymerase chain reaction. Any child who has a change in fecal vaccine shedding status, from negative at baseline (6 weeks) to positive at any subsequent time point, will be categorized as having met the outcome measure for positive fecal vaccine shedding.
Time Frame
Measured through week 12 of life
Title
Number (or Percentage) of Infants in Each Study Arm With Rotavirus-specific Plasma Immunoglobulin A (IgA) Seroconversion Post-vaccination
Description
This outcome will measure seroconversion, i.e. the change in plasma rotavirus-specific IgA concentration at week 14 of life compared to week 6 of life (baseline). Blood will be collected from infants prior to the first dose of Rotarix at week 6 of life and again at week 14 of life (4 weeks following the second dose) for measurement of plasma rotavirus-specific IgA by enzyme immunoassay. Infants will be assessed for seroconversion (IgA concentration <=20 U/mL pre-vaccination and >20 post-vaccination). Infants who demonstrate rotavirus-specific IgA seroconversion will be categorized as having met the outcome measure.
Time Frame
Measured at week 14 of life
Title
Number (or Percentage) of Infants in Each Study Arm With Successful Vaccine Take, Defined as Positive Fecal Vaccine Shedding Post-vaccination OR Rotavirus-specific Plasma IgA Seroconversion Post-vaccination
Description
Vaccine take is an aggregate, dichotomous immunogenicity measure (successful vaccine take vs no vaccine take). Infants positive for either fecal vaccine shedding OR plasma rotavirus-specific IgA seroconversion (as described in Outcomes 1 and 2, respectively) will be categorized as having met the outcome measure of successful vaccine take. Those who met neither outcome will be categorized as no vaccine take.
Time Frame
Measured at week 14 of life

10. Eligibility

Sex
All
Maximum Age & Unit of Time
15 Weeks
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Generally healthy infant (as determined by medical officers) Age 0-7 days at enrolment Mother willing and able to provide signed informed consent Mother willing to allow infant to be vaccinated according to study schedule Mother willing to allow biological specimens, including blood, stool, and saliva, to be collected from infant according to study protocol Mother willing and able to adhere to study schedule Exclusion Criteria: Obvious congenital malformation Birth weight (if known) or enrolment weight (if birth weight unknown) < 2000 gm Known immunocompromising condition in infant Enrolment in other vaccine research trials Other household member enrolled in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Lee, M.D.
Organizational Affiliation
University of Vermont
Official's Role
Principal Investigator
Facility Information:
Facility Name
International Center for Diarrhoeal Disease Research, Bangladesh (icddr,b)
City
Dhaka
Country
Bangladesh

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31607603
Citation
Lee B, Dickson DM, Alam M, Afreen S, Kader A, Afrin F, Ferdousi T, Damon CF, Gullickson SK, McNeal MM, Bak DM, Tolba M, Carmolli MP, Taniuchi M, Haque R, Kirkpatrick BD. The effect of increased inoculum on oral rotavirus vaccine take among infants in Dhaka, Bangladesh: A double-blind, parallel group, randomized, controlled trial. Vaccine. 2020 Jan 3;38(1):90-99. doi: 10.1016/j.vaccine.2019.09.088. Epub 2019 Oct 10.
Results Reference
derived

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The Effects of Increased Inoculum on Oral Rotavirus Vaccine Take and Immunogenicity

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