Shigella Sonnei 53G Human Infection Study in Kenyan Adults

• Status: Not yet recruiting
• Trial end date: 2026-11-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Oxford
• Collaborators: Johns Hopkins University; KEMRI United States Army Medical Research Directorate-Kenya; KEMRI-Wellcome Trust Collaborative Research Program; Naval Medical Research Center; PATH; Walter Reed Army Institute of Research (WRAIR)
• Treatments: Ciprofloxacin

Criteria

Inclusion Criteria:

• Healthy adults between 18 and 45 years of age (inclusive) Kilifi County residents

• Able and willing (in the Investigator's opinion) to comply with all study requirements.

• Provide informed consent.

• Demonstrate comprehension of the protocol procedures and knowledge of study by passing a test of understanding (pass grade 100%).

• Use of effective method of contraception for the entire duration of study (prior to study start and up to study completion) (women only). Female volunteers will be asked to provide their family planning records to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female volunteer's entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).

• Willingness to participate for an inpatient stay lasting approximately 12 days or longer and an outpatient follow-up lasting about 12 months from challenge.

• Available for all planned follow-up visits.

Exclusion Criteria:

• Presence of a significant medical condition (e.g., psychiatric conditions, alcohol or illicit drug abuse/dependency, or gastrointestinal disease, such as peptic ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease, inflammatory bowel disease), or other laboratory abnormalities which in the opinion of the investigator precludes participation in the study.

• Known immunosuppressive illness for example those with cancer, on immunosuppressive therapy, HIV etc.

• Positive serology results for HIV, HBsAg, or HCV antibodies.

• Evidence of inflammatory arthritis on exam and/or HLA-B27 positive.

• Family history of inflammatory arthritis.

• Clinically significant abnormalities in screening lab haematology or serum chemistry, as determined by PI or PI in consultation with the research monitor and Sponsor.

• Known allergies to fluoroquinolones, β-lactams or trimethoprim-sulfamethoxazole (any of the three are exclusionary).

• Fewer than 3 stools per week or more than 3 stools per day as the usual frequency.

• History of diarrhoea in the 2 weeks prior to planned inpatient phase.

• Use of antibiotics during the 7 days before receiving the challenge inoculum dosing.

• Use of prescription and/or OTC medications that contain imodium, acetaminophen, aspirin, ibuprofen, and/or other non-steroidal anti-inflammatory drugs, during the 48 hours prior to investigational product administration.

• Confirmed PCR positive for SARS-COV-2 three days before challenge i.e., Day -3.

• Use of any medication known to affect the immune function within 30 days preceding receipt of the challenge inoculum or planned use during the active study period.

• Serologic evidence of prior S. sonnei infection as determined by ELISA.

• A chronic disease for which doses of prescription medications are not stable for at least the past 3 months.

• Have known immunocompromised household contacts for example those with cancer, on immunosuppressive therapy, HIV etc.

• A clinically significant abnormality on physical examination, including a systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, or a resting pulse >100 beats/min or <55 beats/min (<50 beats/min for conditioned athletes).

• Pregnant, nursing, or planning to become pregnant within 29 days of receipt of the study product.

• In the 4 weeks following challenge, volunteer will be living with or having daily contact with elderly persons aged 70 years or more, diapered individuals, persons with disabilities, children <2 years old, a woman known to be pregnant or nursing, or anyone with diminished immunity. This includes contact at work, home, school, day-care, nursing homes, or similar places.

• Work in a health care setting, day care center, or as a food handler in the 4 weeks following the challenge with S. sonnei.

• Use of any investigational drug or any investigational vaccine within 60 days preceding challenge, or planned use during the 6 months after receipt of the study agent.

• Have received a licensed, live vaccine within 28 days or a licensed inactivated vaccine within 14 days of receiving the challenge inoculum.

• Inability to comply with inpatient rules and regulations.

• Has any other condition that, in the opinion of the Investigator, would jeopardize the safety or rights of a volunteer (e.g., infection with another detected pathogen) or would render the volunteer unable to comply with the protocol.

• Received blood or blood products within the past six months.