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Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA)

Primary Purpose

Typhoid Fever

Status
Enrolling by invitation
Phase
Phase 4
Locations
Ghana
Study Type
Interventional
Intervention
Vi-TT
MCV-A vaccine
Sponsored by
International Vaccine Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Typhoid Fever focused on measuring Typhoid, Typhoid conjugate vaccine, Cluster randomised trial

Eligibility Criteria

9 Months - 15 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet the following criteria:

  • Healthy participants aged 9 months to <16 years (i.e., ≤15 years and 364 days) of age at the time of vaccination
  • Participants/Parents/legally authorized representative (LAR) who have voluntarily given informed assent (sought from participants aged 12 years to <16 years) and informed consent
  • Participants/Parents/LAR living within study target area at the time of vaccination and willing to follow the study procedures and be available for the entire duration of the study

Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study:

  • Known allergy to any vaccine component
  • Self-reported ongoing acute and/or chronic illness
  • Any self-reported coagulopathies
  • Any medical or social compelling reasons in the judgment of a clinical physician
  • Self-reported pregnancy/Positive urine pregnancy test or lactating
  • Previous typhoid vaccination in the last 5 years (proven by the presentation of a vaccine card or self-reporting).

Temporary exclusion criteria

  • Self-reported fever (elevated tympanic (≥38°C) or axillary temperature (≥37.5°C)) within 24 hours of vaccination
  • Self-reported use of antipyretics within 4hours prior to vaccination
  • Any other vaccination during the last 4 weeks (proven by the presentation of a vaccine card or self-reporting)
  • Girls ≥11 years of age with self-reported irregular menstruation or who do not know their last menstruation date

Sites / Locations

  • Kwame Nkrumah University of Science and Technology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Vi-TT Arm

MCV-A arm

Arm Description

A single dose of Vi-TT to children 9 months to 15 years of age.

A single dose of MCV-A vaccine to the comparator group.

Outcomes

Primary Outcome Measures

Total Protection
The incidence of blood culture-confirmed symptomatic TF in all vaccine recipients of the intervention clusters, compared with control clusters.

Secondary Outcome Measures

Safety Assessment
1) Proportion of adverse events in participants receiving Vi-TT compared with MCV-A, measured by: The proportion of participants in each group of a sub-sample of the cohort developing adverse events/adverse reactions within the first 7 days post-vaccination. The proportion of participants in each group of the cohort developing serious adverse events during the entire study period, as determined by self-reporting at follow-up contact.
Overall protection
The incidence of blood culture-confirmed symptomatic TF in all residents of the intervention clusters compared with that in all residents of control clusters
Total protection against severe typhoid.
The incidence of severe TF in vaccinated individuals in intervention clusters compared to control clusters
Total protection against clinical typhoid.
The incidence of clinical typhoid fever cases, defined as persistent fever (tympanic (≥38.0℃) or axillary temperature (≥37.5℃) or reported fever for ≥3 consecutive days) with abdominal complaints at a study surveillance site in vaccinated individuals in intervention clusters compared to control clusters.
Overall protection against clinical typhoid.
The incidence of clinical typhoid fever cases presenting at a study surveillance site among all residents of the Vi-TT clusters compared to the control vaccine clusters.
Indirect Protection aganist Blood Culture Confirmed Typhoid.
The incidence of blood culture-confirmed symptomatic TF in non-vaccinees of the intervention clusters compared with control clusters.
Seroconversion rates
The seroconversion rates as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.
Geometric mean titers
The antibody concentration as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.

Full Information

First Posted
March 17, 2021
Last Updated
December 8, 2021
Sponsor
International Vaccine Institute
Collaborators
Kwame Nkrumah University of Science and Technology, University of Cambridge, International Centre for Diarrhoeal Disease Research, Bangladesh, Fondation Mérieux, University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT04852185
Brief Title
Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana
Acronym
TyVEGHA
Official Title
A Cluster-randomised Controlled Phase IV Trial Assessing the Impact of a Vi-Polysaccharide Conjugate Vaccine in Preventing Typhoid Infection in Asante Akim, Ghana (TyVEGHA)
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Enrolling by invitation
Study Start Date
August 24, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
International Vaccine Institute
Collaborators
Kwame Nkrumah University of Science and Technology, University of Cambridge, International Centre for Diarrhoeal Disease Research, Bangladesh, Fondation Mérieux, University of Maryland, Baltimore

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
A cluster-randomised controlled Phase IV trial (cRCT) assessing the impact of a Vi-Polysaccharide conjugate vaccine in preventing typhoid infection in Asante Akim, Ghana (TyVEGHA) with a primary endpoint of determining the total protection conferred by single-dose vaccination with Vi-TT against blood culture-confirmed symptomatic S. Typhi infection in the intervention vaccine clusters, compared with the control vaccine clusters.
Detailed Description
Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), the uptake of these vaccines in African countries has remained low. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, are critical to enhancing the introduction of TCVs in high-burden settings. Here we describe a cluster-randomized trial to investigate population-level protection of TCV against blood culture-confirmed typhoid fever. A total of 80 geographically distinct clusters have been delineated within the Agogo district of the Asante Akim region in Ghana. Clusters will be randomized to the intervention arm receiving TCV or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the overall protection of TCV against blood culture-confirmed typhoid fever. Total, direct, and indirect protection will be measured as secondary outcomes. Blood culture-based enhanced surveillance will enable the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs will improve uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Typhoid Fever
Keywords
Typhoid, Typhoid conjugate vaccine, Cluster randomised trial

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Participant- and observer-blinded, cluster-randomised controlled Phase IV trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
23000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Vi-TT Arm
Arm Type
Experimental
Arm Description
A single dose of Vi-TT to children 9 months to 15 years of age.
Arm Title
MCV-A arm
Arm Type
Active Comparator
Arm Description
A single dose of MCV-A vaccine to the comparator group.
Intervention Type
Biological
Intervention Name(s)
Vi-TT
Intervention Description
Single-dose V-TT administered to children and adolescents between the ages of 9 months to 15 years.
Intervention Type
Biological
Intervention Name(s)
MCV-A vaccine
Intervention Description
Single-dose of MCV-A vaccine (a meningococcal vaccine)
Primary Outcome Measure Information:
Title
Total Protection
Description
The incidence of blood culture-confirmed symptomatic TF in all vaccine recipients of the intervention clusters, compared with control clusters.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Safety Assessment
Description
1) Proportion of adverse events in participants receiving Vi-TT compared with MCV-A, measured by: The proportion of participants in each group of a sub-sample of the cohort developing adverse events/adverse reactions within the first 7 days post-vaccination. The proportion of participants in each group of the cohort developing serious adverse events during the entire study period, as determined by self-reporting at follow-up contact.
Time Frame
3 years
Title
Overall protection
Description
The incidence of blood culture-confirmed symptomatic TF in all residents of the intervention clusters compared with that in all residents of control clusters
Time Frame
3 years
Title
Total protection against severe typhoid.
Description
The incidence of severe TF in vaccinated individuals in intervention clusters compared to control clusters
Time Frame
3 years
Title
Total protection against clinical typhoid.
Description
The incidence of clinical typhoid fever cases, defined as persistent fever (tympanic (≥38.0℃) or axillary temperature (≥37.5℃) or reported fever for ≥3 consecutive days) with abdominal complaints at a study surveillance site in vaccinated individuals in intervention clusters compared to control clusters.
Time Frame
3 years
Title
Overall protection against clinical typhoid.
Description
The incidence of clinical typhoid fever cases presenting at a study surveillance site among all residents of the Vi-TT clusters compared to the control vaccine clusters.
Time Frame
3 years
Title
Indirect Protection aganist Blood Culture Confirmed Typhoid.
Description
The incidence of blood culture-confirmed symptomatic TF in non-vaccinees of the intervention clusters compared with control clusters.
Time Frame
3 years
Title
Seroconversion rates
Description
The seroconversion rates as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.
Time Frame
3 years
Title
Geometric mean titers
Description
The antibody concentration as measured by enzyme linked immunosorbent assay (anti-Vi IgM and IgG) for S. Typhi and iNTS at defined time points in a age-stratified subset of intervention and control vaccinees.
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
9 Months
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet the following criteria: Healthy participants aged 9 months to <16 years (i.e., ≤15 years and 364 days) of age at the time of vaccination Participants/Parents/legally authorized representative (LAR) who have voluntarily given informed assent (sought from participants aged 12 years to <16 years) and informed consent Participants/Parents/LAR living within study target area at the time of vaccination and willing to follow the study procedures and be available for the entire duration of the study Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participation in this study: Known allergy to any vaccine component Self-reported ongoing acute and/or chronic illness Any self-reported coagulopathies Any medical or social compelling reasons in the judgment of a clinical physician Self-reported pregnancy/Positive urine pregnancy test or lactating Previous typhoid vaccination in the last 5 years (proven by the presentation of a vaccine card or self-reporting). Temporary exclusion criteria Self-reported fever (elevated tympanic (≥38°C) or axillary temperature (≥37.5°C)) within 24 hours of vaccination Self-reported use of antipyretics within 4hours prior to vaccination Any other vaccination during the last 4 weeks (proven by the presentation of a vaccine card or self-reporting) Girls ≥11 years of age with self-reported irregular menstruation or who do not know their last menstruation date
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Florian Marks, PhD
Organizational Affiliation
University of Cambridge
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ellis Owusu Dabo, PhD
Organizational Affiliation
Kwame Nkrumah University of Science and Technology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kwame Nkrumah University of Science and Technology
City
Kumasi
State/Province
Ashanti
ZIP/Postal Code
PMB
Country
Ghana

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Sharing can be considered on a case-by-case basis considering the intended use and impact.

Learn more about this trial

Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana

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