ZyVac-TCV Bangladesh Study

NCT06757283 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: PR-24059
• Study Type: interventional
• Target: 4,000
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective closed cohort, open-label, phase III effectiveness study using a test-negative design of a typhoid conjugate vaccine, ZyVac® TCV (purified Vi capsular polysaccharide of Salmonella Typhi conjugated to tetanus toxoid as carrier protein), manufactured by Zydus Lifesciences Limited. The study will be conducted in a closed cohort population among children aged 6 months to 15 years residing in wards 5, 6, 7, 48, 49, 50, 63, 71, and 72 of Dhaka South City Corporation (DSCC). The targeted number of age-eligible children in the study area is \~92,000 among them \~60,000 will be vaccinated. A subset of the first 600 consenting participants will be selected by age strata (6 months to \<2 years, 2-4 years, 5-15 years) for enrollment in the immunogenicity study with an additional three follow-up visits. Diary cards will be used to collect adverse events (AEs) following immunization (AEFI) data up to day 7 for a subset of active follow-up of the first 600 vaccinated participants. Participants not in this subset will be encouraged to go to the 'Adverse Event Monitoring Cell' at the Maniknagar field office. Data on serious adverse events (SAEs) will be reported for six months after vaccination. All study updates including AEs and SAEs will be reported to the data safety and monitoring board (DSMB) and sponsor. Passive surveillance for typhoid fever will be carried out in the Maniknagar field office and Mugda Medical College and Hospital in the catchment area among the age-eligible children.

Conditions

Typhoid Vaccination; Typhoid; Typhoid Fever

Keywords

Conjugate vaccine; Immunogenicity; Safety; Typhoid fever; Bangladesh; Children

Outcome Measures

Primary Outcomes (1)

• Primary outcome

  Blood culture-confirmed typhoid fever

  12 months

Secondary Outcomes (2)

• Secondary outcome

  12 months

• Secondary outcome

  12 months

Study Arms (2)

Culture-positive case

EXPERIMENTAL

Eligible febrile patients who will be positive by blood culture for Salmonella enterica serotype Typhi and symptoms developed \>14 days after vaccination, or, if unvaccinated, \>14 days after the midpoint of the vaccination period.

Biological: Purified Vi capsular polysaccharide of Salmonella typhi conjugated to tetanus toxoid as carrier protein (Typhoid Vi Conjugate Vaccine I.P.). Trade name: ZyVac® TCV

Culture-negative control

ACTIVE COMPARATOR

Eligible febrile patients who will be negative by blood culture for Salmonella enterica serotype Typhi and symptoms developed \>14 days after vaccination, or, if unvaccinated, \>14 days after the midpoint of the vaccination period.

Biological: Purified Vi capsular polysaccharide of Salmonella typhi conjugated to tetanus toxoid as carrier protein (Typhoid Vi Conjugate Vaccine I.P.). Trade name: ZyVac® TCV

Interventions

Purified Vi capsular polysaccharide of Salmonella typhi conjugated to tetanus toxoid as carrier protein (Typhoid Vi Conjugate Vaccine I.P.). Trade name: ZyVac® TCV BIOLOGICAL

Purified Vi capsular polysaccharide of Salmonella typhi conjugated to tetanus toxoid as carrier protein (Typhoid Vi Conjugate Vaccine I.P.)

Culture-negative control; Culture-positive case

Eligibility Criteria

• Age: 6 Months - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Participant was included in the baseline list of the study population
• Participants living within the study catchment area at the time of vaccination
• Parent/guardian is willing and competent to provide informed consent (if the participant is 11 to 15 years of age, assent will also be sought)
• Participants aged between 6 months to15 years (i.e. up to 15 years 364 days) at the time of vaccination
• Apparently healthy (no complaints of febrile illness) on the day of vaccination
• Parent/guardian confirms that their child will be willing and be able to comply with study requirements

You may not qualify if:

• Has knowingly received a typhoid vaccine in the past
• Known allergy to any vaccine in the past
• Medical or social reasons that will prevent the participant from conforming to the study requirements as judged by a medical professional
• Planning to move away from the catchment area within the next 12 months
• Pregnant at the time of vaccination, as confirmed by a urine test (urine pregnancy test will be done in girls who are married)
• Confirmed or suspected immunosuppressive or immunodeficiency disorder; or subjects on any immunosuppressive or immunostimulant therapy
• Subject participated in another clinical study in the past 3 months

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Zydus Lifesciences Limited: collaborator

Study Sites (1)

International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, Bangladesh

Location

Related Links

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• Ochiai, R.L., et al., A study of typhoid fever in five Asian countries: disease burden and implications for controls.
• World Health, O., Typhoid vaccines: WHO position paper, March 2018 - Recommendations.
• Qamar, F.N., et al., Adverse events following immunization with typhoid conjugate vaccine in an outbreak setting in Hyderabad, Pakistan.
• TyVAC. Currently available typhoid vaccines. 2023
• GAVI. Typhoid conjugate vaccine (TCV) support. \[cited 2024 14 April\]
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• Mond, J.J., A. Lees, and C.M. Snapper, T cell-independent antigens type 2.
• Weintraub, A., Immunology of bacterial polysaccharide antigens.
• Acharya, I.L., et al., Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi.
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• Olanratmanee, T., et al., Safety and immunogenicity of Salmonella typhi Ty21a liquid formulation vaccine in 4- to 6-year-old Thai children.
• Szu, S.C., et al., Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines.
• Lin, F.Y., et al., The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children.
• Thiem, V.D., et al., The Vi conjugate typhoid vaccine is safe, elicits protective levels of IgG anti-Vi, and is compatible with routine infant vaccines.
• Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study
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• WHO. Weekly Epidemiological Record. 2017; 2:13-20. 2007
• Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children.
• Qadri, F., et al., Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.
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• WHO. INFORMATION SHEET OBSERVED RATE OF VACCINE REACTIONS TYPHOID VACCINE
• Ng'eno, E., et al., Dynamic Incidence of Typhoid Fever over a 10-Year Period (2010-2019) in Kibera, an Urban Informal Settlement in Nairobi, Kenya.
• ASTMH
• Limited, Z.L. Summary of Product Characteristics as per Annexure C Typhoid vi Conjugate Vaccine I.P. ZyVac® TCV.
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MeSH Terms

Conditions

Typhoid Fever

Interventions

Carrier Proteins

Condition Hierarchy (Ancestors)

Salmonella Infections; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins

Central Study Contacts

Farhana Khanam, MPhil,PhD

CONTACT

+8801755532548; farhanak@icddrb.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a phase III effectiveness study of the typhoid conjugate vaccine (Vi-TCV) (ZyVac® TCV). The study will be conducted in a closed cohort population of children aged 6 months to 15 years residing in a selected geographical catchment area in Dhaka, Bangladesh using a test-negative design (TND).

Study Record Dates

• First Submitted: December 20, 2024
• First Posted: January 3, 2025
• Study Start: April 1, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): May 30, 2026
• Last Updated: February 7, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)