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

NCT02992197 | Completed Phase 4 Results DMC

• 1 other identifier: CHRMS 17-0166
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

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.

Conditions

Rotavirus Infection; Vaccine Response Impaired; Vaccine Virus Shedding

Keywords

Rotavirus; Oral vaccines; Vaccine underperformance; Vaccine shedding

Outcome Measures

Primary Outcomes (3)

• 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.

  Measured through week 12 of life

• 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.

  Measured at week 14 of life

• 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.

  Measured at week 14 of life

Study Arms (2)

Rotarix, single dose

ACTIVE COMPARATOR

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

Biological: Rotarix, dose 1; Drug: Placebo (for Rotarix dose 2)

Rotarix, double dose

EXPERIMENTAL

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

Biological: Rotarix, dose 1; Biological: Rotarix, dose 2

Interventions

Rotarix, dose 1 BIOLOGICAL

Rotarix, dose 1

Rotarix, double dose; Rotarix, single dose

Rotarix, dose 2 BIOLOGICAL

Rotarix, dose 2

Rotarix, double dose

Placebo (for Rotarix dose 2) DRUG

Sterile water to provide volume equivalent as a second dose of Rotarix

Rotarix, single dose

Eligibility Criteria

• Age: Up to 15 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Vermont: lead
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator
• Charles H. Hood Foundation: collaborator
• Thrasher Research Fund: collaborator

Study Sites (1)

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

Dhaka, Bangladesh

Location

Related Publications (1)

• 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.

  PMID: 31607603 DERIVED

MeSH Terms

Conditions

Rotavirus Infections

Interventions

RIX4414 vaccine

Condition Hierarchy (Ancestors)

Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Benjamin Lee
• Organization: The University of Vermont College of Medicine

blee7@uvm.edu

8026567748

Study Officials

• Benjamin Lee, M.D.

  University of Vermont

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Pediatrics

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 14, 2016
• Study Start: June 12, 2017
• Primary Completion: June 7, 2018
• Study Completion: June 7, 2018
• Last Updated: August 4, 2020
• Results First Posted: July 17, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)