Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi

NCT03299426 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: HP-00076625
• Study Type: interventional
• Target: 30,000
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy of a Typhoid conjugate vaccine (Vi-TCV) in Malawi, Africa among children age 9 months through 12 years. Participants will be randomized in a 1:1 ration to receive the study vaccine or the control vaccine (meningococcal group A conjugate vaccine - MCV-A).

Conditions

Typhoid

Keywords

Typhoid; Typhoid in Malawi; Typhoid Vaccine

Outcome Measures

Primary Outcomes (1)

• Efficacy of Vi-TCV

  The primary outcome of interest is the incidence of blood culture-positive typhoid fever among Vi-TCV and MCV-A vaccine recipients in the study population during the entire post-vaccination surveillance period. Vaccine efficacy will be calculated as one minus the relative rate of symptomatic typhoid fever in the Vi-TCV group compared to that in the MCV-A group.

  Up to 36 months

Secondary Outcomes (3)

• Safety of Vi-TCV

  6 months

• Immunogenicity of Vi-TCV

  28 days

• Number of typhoid fever cases prevented Vi-TCV

  Up to 36 months

Study Arms (2)

Vi-Typhoid Conjugate Vaccine (Vi-TCV)

EXPERIMENTAL

Children will receive a single 0.5-ml dose of Vi-TCV administered by the intramuscular route.

Biological: Vi-Typhoid Conjugate Vaccine (Vi-TCV)

Meningococcal A Conjugate Vaccine (MCV-A)

ACTIVE COMPARATOR

Children will receive a single dose of MCV-A administered by the intramuscular route. Children 9-11 months will receive a 5µg/0.5ml dose. Children 12 months and older will receive a 10µg/0.5 ml dose.

Biological: Meningococcal A Conjugate Vaccine (MCV-A)

Interventions

Vi-Typhoid Conjugate Vaccine (Vi-TCV) BIOLOGICAL

Single 0.5-ml intramuscular injection

Vi-Typhoid Conjugate Vaccine (Vi-TCV)

Meningococcal A Conjugate Vaccine (MCV-A) BIOLOGICAL

Single intramuscular injection. Children 9-11 months will receive a 5µg/0.5ml dose. Children 12 months and older will receive a 10µg/0.5 ml dose.

Meningococcal A Conjugate Vaccine (MCV-A)

Eligibility Criteria

• Age: 9 Months - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy male or female child between the ages of 9 months and 12 years/364 days at the time of study vaccination.
• A child whose parent or guardian resides primarily within the Ndirande or Zingwangwa study areas at the time of study vaccinations and who intends to be present in the area for the duration of the trial.
• A child whose parent or guardian has voluntarily given informed consent.

You may not qualify if:

• History of documented hypersensitivity to any component of the vaccine
• Prior receipt of any typhoid vaccine in the past 3 years
• History of severe allergic reaction with generalized urticarial, angioedema, or anaphylaxis
• Any condition determined by the investigator to be likely to interfere with evaluation of the vaccine or to be a significant potential health risk to the child or make it unlikely that the child would complete the study.
• Reported fever within 24 hours prior to vaccination
• Use of anti-pyretics within 4 hours prior to vaccination
• \- Receipt of measles vaccine in the one month prior to enrollment, as determined by parental history or vaccination card.
• Known history of diabetes, tuberculosis, cancer, chronic kidney, heart, or liver disease, progressive neurological disorders, poorly controlled seizures, or terminal illness
• Severe malnutrition as determined by MUAC\< 12.5 cm for children younger than 5 years;
• Receipt of any other investigational intervention in the last 6 months or anticipated during the course of the study.
• Receipt of blood products in the last 6 months.
• Known HIV-infection or exposure or other immunosuppressive conditions.
• Receipt of systemic immunosuppressant or systemic corticosteroids.
• Receipt of any measles-containing vaccine for children younger than 1 year of age

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Bill and Melinda Gates Foundation: collaborator
• Malawi-Liverpool-Wellcome Trust Clinical Research Programme: collaborator
• University College, London: collaborator
• University of Malawi: collaborator

Study Sites (1)

Malawi Liverpool Wellcome Trust Clinical Research Programme, Queen Elizabeth Central Hospital College of Medicine

Blantyre, P.O. Box 30096, Malawi

Location

Related Publications (4)

• Patel PD, Liang Y, Meiring JE, Chasweka N, Patel P, Misiri T, Mwakiseghile F, Wachepa R, Banda HC, Shumba F, Kawalazira G, Dube Q, Nampota-Nkomba N, Nyirenda OM, Girmay T, Datta S, Jamka LP, Tracy JK, Laurens MB, Heyderman RS, Neuzil KM, Gordon MA; TyVAC team. Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children. Lancet. 2024 Feb 3;403(10425):459-468. doi: 10.1016/S0140-6736(23)02031-7. Epub 2024 Jan 25.

  PMID: 38281499 DERIVED

• Nampota-Nkomba N, Nyirenda OM, Khonde L, Mapemba V, Mbewe M, Ndaferankhande JM, Msuku H, Masesa C, Misiri T, Mwakiseghile F, Patel PD, Patel P, Johnson-Mayo I, Pasetti MF, Heyderman RS, Tracy JK, Datta S, Liang Y, Neuzil KM, Gordon MA, Laurens MB; Typhoid Vaccine Acceleration Consortium team. Safety and immunogenicity of a typhoid conjugate vaccine among children aged 9 months to 12 years in Malawi: a nested substudy of a double-blind, randomised controlled trial. Lancet Glob Health. 2022 Sep;10(9):e1326-e1335. doi: 10.1016/S2214-109X(22)00275-3.

  PMID: 35961356 DERIVED

• Patel PD, Patel P, Liang Y, Meiring JE, Misiri T, Mwakiseghile F, Tracy JK, Masesa C, Msuku H, Banda D, Mbewe M, Henrion M, Adetunji F, Simiyu K, Rotrosen E, Birkhold M, Nampota N, Nyirenda OM, Kotloff K, Gmeiner M, Dube Q, Kawalazira G, Laurens MB, Heyderman RS, Gordon MA, Neuzil KM; TyVAC Malawi Team. Safety and Efficacy of a Typhoid Conjugate Vaccine in Malawian Children. N Engl J Med. 2021 Sep 16;385(12):1104-1115. doi: 10.1056/NEJMoa2035916.

  PMID: 34525285 DERIVED

• Meiring JE, Laurens MB, Patel P, Patel P, Misiri T, Simiyu K, Mwakiseghile F, Tracy JK, Masesa C, Liang Y, Henrion M, Rotrosen E, Gmeiner M, Heyderman R, Kotloff K, Gordon MA, Neuzil KM. Typhoid Vaccine Acceleration Consortium Malawi: A Phase III, Randomized, Double-blind, Controlled Trial of the Clinical Efficacy of Typhoid Conjugate Vaccine Among Children in Blantyre, Malawi. Clin Infect Dis. 2019 Mar 7;68(Suppl 2):S50-S58. doi: 10.1093/cid/ciy1103.

  PMID: 30845320 DERIVED

MeSH Terms

Conditions

Typhoid Fever

Condition Hierarchy (Ancestors)

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

Study Officials

• Matthew Laurens, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 3, 2017
• Study Start: February 21, 2018
• Primary Completion: January 30, 2025
• Study Completion (Estimated): January 30, 2027
• Last Updated: May 12, 2026

Record last verified: 2025-05

Locations

MA (1)