NCT05959616

Shigella Sonnei 53G Human Infection Study in Kenyan Adults

Safety and Feasibility of a Shigella Sonnei 53G Controlled Human Infection Model in Kenyan Adults: a Dose Finding and Dose Verification Study

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: University of Oxford · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

Diarrhoea caused by Shigella (shigellosis) is of major public health importance. However, there are no licensed Shigella vaccines in routine use, with several candidates still in various stages of clinical development. Shigella human infection studies (HIS) have played a key role in vaccine development. These models also allow for the evaluation of immunity and other non-immunological parameters that are important to understand resistance and/or susceptibility to disease. This is particularly useful in individuals from endemic areas with varying levels of prior exposure and immunity to Shigella. Thus, establishing a Shigella HIS would enable the testing of interventions such as vaccines in a population that would most benefit from a subsequent vaccine and has potential to accelerate vaccine development. Here, the goal is to successfully establish a Shigella sonnei human infection model in Kenyan adults. This will be achieved by conducting dose-finding and dose verification Shigella studies that safely and reproducibly induce ≥60% attack rates. In this study, investigators aim to use Shigella HIS in healthy adults to develop a model as a platform to test vaccines, to study immune responses identifying potential correlates of infection, and non-immunological factors mediating and influencing susceptibility to disease. To achieve this, the study will be carried out in two phases over a period of 12-14 months. Phase A will enroll (N=up to 40 volunteers) and Phase B will enroll an additional (N=30 volunteers). To be eligible to receive a dose of 53G, volunteers must pass the screening visit. Investigators will vary the dose of bacteria in individuals enrolled for challenge to identify the dose needed to cause ≥60% shigellosis (attack rate) (Phase A) followed by testing and demonstrate the reproducibility of the model (Phase B). Thus, the main outcomes of the study will be: (1) optimisation of bacterial dose for infection success (≥60% attack rate); and (2) safety.

Detailed description

This is a Phase 1 dose finding and dose verification study which will be used to determine the dose of S. sonnei 53G that induces the primary outcome in approximately ≥60% of Kenyan adult volunteers. This study will occur in two phases, Phase A (dose-finding) with up to 40 volunteers challenged with 53G and Phase B (dose verification) with N=30 volunteers planned to be administered 53G. Based on previously published data using this model, 1,500 colony-forming units (CFU) will be the dose administered to the first cohort. Dosing of subsequent cohorts will depend on results of the previous cohort. If a lower-than-expected attack rate (AR) occurs, the dose for the next cohort will be increased by 500 CFU. Conversely, if the AR is higher than expected the dose for the next cohort will be decreased by 500 CFU. Cohorts of volunteers will continue to be challenged until either; a dose that reproducibly causes infection in at least 60% of volunteers; safety precludes continuing (\>90% AR at 500 CFU) or futility (an AR of 60% is unable to be achieved, even with a 3000 CFU dose). It may take more or less than 3 dose-finding groups to find the optimal dose for which the primary outcome (shigellosis) is achieved in approximately ≥60% of the volunteers and thus the total number of volunteers enrolled in both phases may be less or more than N=60. Once the optimal dose is established in Phase A, that dose will be carried forward for verification in Phase B. For Phase B, dose verification groups of 30 volunteers (2 cohorts of 15 volunteers per cohort) will be conducted to verify the AR with the chosen dose. The dose finding and verification stages will be done in a staggered fashion in case the dose needs to be adjusted, resulting in approximately 5 cohorts to be enrolled over time. Allocation into the groups will be on "first come first served basis" with no randomization occurring for enrolment in any of the cohorts.

Conditions

• Shigellosis

Interventions

Type	Name	Description
BIOLOGICAL	Shigella sonnei 53G	Lyophilized S. sonnei 53G strain (Lot 1794)
DRUG	Ciprofloxacin 500 mg	Ciprofloxacin (500 mg orally twice daily for three days),

Timeline

• Start date: 2025-01-21
• Primary completion: 2026-04-30
• Completion: 2027-08-30
• First posted: 2023-07-25
• Last updated: 2025-03-13

Locations

1 site across 1 country: Kenya