Shigella Sonnei 53G Human Infection Study in Kenyan Adults

NCT05959616 | Recruiting Phase 1 DMC

• 1 other identifier: OxTREC27-22
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Shigellosis

Outcome Measures

Primary Outcomes (2)

• Number of volunteers with solicited adverse events

  Occurrence and severity of solicited adverse events (AEs) through 11 days post-challenge. Occurrence, severity, and relatedness of unsolicited AEs through 11 days post-challenge. Occurrence, severity, and relatedness of serious adverse events (SAEs) throughout the entire study. Occurrence of abnormal clinical laboratory values within 11 days post challenge. Percent of volunteers with nausea, vomiting, anorexia, abdominal pain/cramps rated as moderate to severe.

  Through 11 days post challenge

• Number of volunteers with an attack rate of ≥60%

  Confirmation of the dose with an acceptable safety profile as determined by that gives an attack rate of ≥60% of shigellosis in Kenyan adults.

  Through 11 days post challenge

Secondary Outcomes (3)

• Percent of volunteers with

  Through 11 days post challenge

• Percent of volunteers shedding

  Through 11 days post challenge

• Kinetics of serum IgA and IgG antibody responses

  From baseline to 366 days

Study Arms (6)

Group 1 Shigella sonnei 53G 1500CFU (N=10)

EXPERIMENTAL

Dose finding group Group 1 will receive lyophilised S. sonnei 53G strain at a dose of 1500CFU. Group 1 will receive curative treatment of Ciprofloxacin.

Biological: Shigella sonnei 53G; Drug: Ciprofloxacin 500 mg

Group 2 Shigella sonnei 53G 2000CFU (N=10)

EXPERIMENTAL

Dose finding group Group 2 will receive lyophilised S. sonnei 53G strain at a dose of 2000CFU. Group 2 will receive curative treatment of Ciprofloxacin.

Biological: Shigella sonnei 53G; Drug: Ciprofloxacin 500 mg

Group 3 Shigella sonnei 53G 2500CFU (N=10)

EXPERIMENTAL

Dose finding group Group 3 will receive lyophilised S. sonnei 53G strain at a dose of 2500CFU. Group 3 will receive curative treatment of Ciprofloxacin.

Biological: Shigella sonnei 53G; Drug: Ciprofloxacin 500 mg

Group 4 Shigella sonnei 53G 3000CFU (N=10)

EXPERIMENTAL

Dose finding group Group 4 will receive lyophilised S. sonnei 53G strain at a dose of 3000CFU. Group 4 will receive curative treatment of Ciprofloxacin.

Biological: Shigella sonnei 53G; Drug: Ciprofloxacin 500 mg

Group 5 Shigella sonnei 53G TBDCFU (N=15)

EXPERIMENTAL

Dose verification group Group 5 will receive lyophilised S. sonnei 53G strain at a dose TBD. Group 5 will receive curative treatment of Ciprofloxacin.

Biological: Shigella sonnei 53G; Drug: Ciprofloxacin 500 mg

Group 6 Shigella sonnei 53G TBDCFU (N=15)

EXPERIMENTAL

Dose verification group Group 6 will receive lyophilised S. sonnei 53G strain at a dose TBD. Group 6 will receive curative treatment of Ciprofloxacin.

Biological: Shigella sonnei 53G; Drug: Ciprofloxacin 500 mg

Interventions

Shigella sonnei 53G BIOLOGICAL

Lyophilized S. sonnei 53G strain (Lot 1794)

Group 1 Shigella sonnei 53G 1500CFU (N=10); Group 2 Shigella sonnei 53G 2000CFU (N=10); Group 3 Shigella sonnei 53G 2500CFU (N=10); Group 4 Shigella sonnei 53G 3000CFU (N=10); Group 5 Shigella sonnei 53G TBDCFU (N=15); Group 6 Shigella sonnei 53G TBDCFU (N=15)

Ciprofloxacin 500 mg DRUG

Ciprofloxacin (500 mg orally twice daily for three days),

Group 1 Shigella sonnei 53G 1500CFU (N=10); Group 2 Shigella sonnei 53G 2000CFU (N=10); Group 3 Shigella sonnei 53G 2500CFU (N=10); Group 4 Shigella sonnei 53G 3000CFU (N=10); Group 5 Shigella sonnei 53G TBDCFU (N=15); Group 6 Shigella sonnei 53G TBDCFU (N=15)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Oxford: lead
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator
• KEMRI United States Army Medical Research Directorate-Kenya: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator
• Naval Medical Research Center: collaborator
• PATH: collaborator
• Johns Hopkins University: collaborator

Study Sites (1)

KEMRI-Wellcome Trust Research Programme

Kilifi, 80108, Kenya

RECRUITING

MeSH Terms

Conditions

Dysentery, Bacillary

Interventions

Ciprofloxacin

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 25, 2023
• Study Start: January 21, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): August 30, 2027
• Last Updated: March 13, 2025

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Within 2 years of the study completion date

Locations

KE (1)