PEDVAC iNTS

A Phase lla observer-blind, randomized, controlled, age-de-escalation, single center interventional study to evaluate the safety, reactogenicity, and immune response of the GVGH iNTS vaccine against S. Typhimurium and S. Enteritidis, in adults, children and infants, including dose-finding in infants, in Africa

Background

Invasive Non-typhoidal Salmonella (iNTS) infections, primarily caused by Salmonella Typhimurium and Salmonella Enteritidis, are a major public health concern in sub-Saharan Africa, especially among young children. In response, the GSK Vaccines Institute for Global Health (GVGH) has developed a bivalent iNTS vaccine using Generalized Modules for Membrane Antigens (GMMA) technology.

This Phase IIa interventional study will be conducted in Ghana and aims to assess the safety, immunogenicity, and optimal dosing of the iNTS-GMMA vaccine. The study will follow an age de-escalation and dose-finding design involving approximately 516 healthy participants across four age groups: adults (18–50 years), children (24–59 months), infants (9 months), and infants (6 weeks). Participants will receive varying doses (low, medium, high) of the vaccine or control vaccines, with safety monitored by internal review committees.

The trial is designed to support progression to later-phase trials by identifying the most suitable dose of the iNTS-GMMA vaccine for infants 6 weeks of age—the primary target population for routine immunization in low-resource settings.

Objectives

Main Objective:

• To identify the preferred dose of each component of the iNTS-GMMA vaccine (Dose A [low], Dose B [medium], or Dose C [high]) for infant participants aged 6 weeks.

Specific Objectives:

1. Determine the optimal vaccine dose for infants 6 weeks of age.
2. Assess the safety and reactogenicity of the iNTS-GMMA vaccine across all participant groups.
3. Evaluate the immunogenicity of the vaccine in all participants.
4. Assess seroresponse after each administration of the vaccine.
5. Evaluate the immunogenicity of coadministered routine vaccines (Hepatitis B, Hib, Measles-Rubella) in a subset of infants.
6. Assess the seroresponse to the coadministered vaccines in the same subset.
7. Evaluate seroresponse 6 months after the primary iNTS-GMMA vaccination series in infants.
8. Further characterize immunogenicity and seroresponse to vaccines administered at 14 weeks in infants.
9. Characterize the immune response to the iNTS-GMMA vaccine in the dose-finding infant cohort.
10. Evaluate the innate immune response across safety cohorts (adults, children, and infants).

Funding Partners: GSK Vaccines Institute for Global Health (GVGH), Siena, Italy and European &
Developing Countries Clinical Trials Partnership (EDCTP) with International Vaccine Institute (IVI)